Author: "Ensell L" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Ensell L"' showing total 31 results

Start Over Author "Ensell L"

31 results on '"Ensell L"'

1. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Author: Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., Swanton C., Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., and Swanton C.
Abstract: The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.
Published: 2024

2. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

Author: Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., Moore D. A., Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., and Moore D. A.
Abstract: The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma.
Published: 2024

3. Body composition and lung cancer-associated cachexia in TRACERx

Author: Al-Sawaf, O, Weiss, J, Skrzypski, M, Lam, J, Karasaki, T, Zambrana, F, Kidd, A, Frankell, A, Watkins, T, Martinez-Ruiz, C, Puttick, C, Black, J, Huebner, A, Bakir, M, Sokac, M, Collins, S, Veeriah, S, Magno, N, Naceur-Lombardelli, C, Prymas, P, Toncheva, A, Ward, S, Jayanth, N, Salgado, R, Bridge, C, Christiani, D, Mak, R, Bay, C, Rosenthal, M, Sattar, N, Welsh, P, Liu, Y, Perrimon, N, Popuri, K, Beg, M, Mcgranahan, N, Hackshaw, A, Breen, D, O'Rahilly, S, Birkbak, N, Aerts, H, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Kisistok, J, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Moore, D, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Cadieux, E, Lim, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Pich, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Swanton, C, Al-Sawaf O., Weiss J., Skrzypski M., Lam J. M., Karasaki T., Zambrana F., Kidd A. C., Frankell A. M., Watkins T. B. K., Martinez-Ruiz C., Puttick C., Black J. R. M., Huebner A., Bakir M. A., Sokac M., Collins S., Veeriah S., Magno N., Naceur-Lombardelli C., Prymas P., Toncheva A., Ward S., Jayanth N., Salgado R., Bridge C. P., Christiani D. C., Mak R. H., Bay C., Rosenthal M., Sattar N., Welsh P., Liu Y., Perrimon N., Popuri K., Beg M. F., McGranahan N., Hackshaw A., Breen D. M., O'Rahilly S., Birkbak N. J., Aerts H. J. W. L., Aerts H. J., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Kisistok J., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Moore D. A., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Cadieux E. L., Lim E. L., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Pich O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., Swanton C., Al-Sawaf, O, Weiss, J, Skrzypski, M, Lam, J, Karasaki, T, Zambrana, F, Kidd, A, Frankell, A, Watkins, T, Martinez-Ruiz, C, Puttick, C, Black, J, Huebner, A, Bakir, M, Sokac, M, Collins, S, Veeriah, S, Magno, N, Naceur-Lombardelli, C, Prymas, P, Toncheva, A, Ward, S, Jayanth, N, Salgado, R, Bridge, C, Christiani, D, Mak, R, Bay, C, Rosenthal, M, Sattar, N, Welsh, P, Liu, Y, Perrimon, N, Popuri, K, Beg, M, Mcgranahan, N, Hackshaw, A, Breen, D, O'Rahilly, S, Birkbak, N, Aerts, H, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Kisistok, J, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Moore, D, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Cadieux, E, Lim, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Pich, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Swanton, C, Al-Sawaf O., Weiss J., Skrzypski M., Lam J. M., Karasaki T., Zambrana F., Kidd A. C., Frankell A. M., Watkins T. B. K., Martinez-Ruiz C., Puttick C., Black J. R. M., Huebner A., Bakir M. A., Sokac M., Collins S., Veeriah S., Magno N., Naceur-Lombardelli C., Prymas P., Toncheva A., Ward S., Jayanth N., Salgado R., Bridge C. P., Christiani D. C., Mak R. H., Bay C., Rosenthal M., Sattar N., Welsh P., Liu Y., Perrimon N., Popuri K., Beg M. F., McGranahan N., Hackshaw A., Breen D. M., O'Rahilly S., Birkbak N. J., Aerts H. J. W. L., Aerts H. J., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Kisistok J., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Moore D. A., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Cadieux E. L., Lim E. L., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Pich O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., and Swanton C.
Abstract: Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial–mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC.
Published: 2023

4. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author: Karasaki, T, Moore, D, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Magno, N, Ward, S, Bakir, M, Watkins, T, Grigoriadis, K, Huebner, A, Hill, M, Frankell, A, Abbosh, C, Puttick, C, Zhai, H, Gimeno-Valiente, F, Saghafinia, S, Kanu, N, Dietzen, M, Pich, O, Lim, E, Martinez-Ruiz, C, Black, J, Biswas, D, Campbell, B, Lee, C, Colliver, E, Enfield, K, Hessey, S, Hiley, C, Zaccaria, S, Litchfield, K, Birkbak, N, Cadieux, E, Demeulemeester, J, Van Loo, P, Adusumilli, P, Tan, K, Cheema, W, Sanchez-Vega, F, Jones, D, Rekhtman, N, Travis, W, Hackshaw, A, Marafioti, T, Salgado, R, Le Quesne, J, Nicholson, A, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Castignani, C, Bailey, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Mcgranahan, N, Swanton, C, Jamal-Hanjani, M, Karasaki T., Moore D. A., Veeriah S., Naceur-Lombardelli C., Toncheva A., Magno N., Ward S., Bakir M. A., Watkins T. B. K., Grigoriadis K., Huebner A., Hill M. S., Frankell A. M., Abbosh C., Puttick C., Zhai H., Gimeno-Valiente F., Saghafinia S., Kanu N., Dietzen M., Pich O., Lim E. L., Martinez-Ruiz C., Black J. R. M., Biswas D., Campbell B. B., Lee C., Colliver E., Enfield K. S. S., Hessey S., Hiley C. T., Zaccaria S., Litchfield K., Birkbak N. J., Cadieux E. L., Demeulemeester J., Van Loo P., Adusumilli P. S., Tan K. S., Cheema W., Sanchez-Vega F., Jones D. R., Rekhtman N., Travis W. D., Hackshaw A., Marafioti T., Salgado R., Le Quesne J., Nicholson A. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Castignani C., Bailey C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Kassiotis G., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., McGranahan N., Swanton C., Jamal-Hanjani M., Karasaki, T, Moore, D, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Magno, N, Ward, S, Bakir, M, Watkins, T, Grigoriadis, K, Huebner, A, Hill, M, Frankell, A, Abbosh, C, Puttick, C, Zhai, H, Gimeno-Valiente, F, Saghafinia, S, Kanu, N, Dietzen, M, Pich, O, Lim, E, Martinez-Ruiz, C, Black, J, Biswas, D, Campbell, B, Lee, C, Colliver, E, Enfield, K, Hessey, S, Hiley, C, Zaccaria, S, Litchfield, K, Birkbak, N, Cadieux, E, Demeulemeester, J, Van Loo, P, Adusumilli, P, Tan, K, Cheema, W, Sanchez-Vega, F, Jones, D, Rekhtman, N, Travis, W, Hackshaw, A, Marafioti, T, Salgado, R, Le Quesne, J, Nicholson, A, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Castignani, C, Bailey, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Mcgranahan, N, Swanton, C, Jamal-Hanjani, M, Karasaki T., Moore D. A., Veeriah S., Naceur-Lombardelli C., Toncheva A., Magno N., Ward S., Bakir M. A., Watkins T. B. K., Grigoriadis K., Huebner A., Hill M. S., Frankell A. M., Abbosh C., Puttick C., Zhai H., Gimeno-Valiente F., Saghafinia S., Kanu N., Dietzen M., Pich O., Lim E. L., Martinez-Ruiz C., Black J. R. M., Biswas D., Campbell B. B., Lee C., Colliver E., Enfield K. S. S., Hessey S., Hiley C. T., Zaccaria S., Litchfield K., Birkbak N. J., Cadieux E. L., Demeulemeester J., Van Loo P., Adusumilli P. S., Tan K. S., Cheema W., Sanchez-Vega F., Jones D. R., Rekhtman N., Travis W. D., Hackshaw A., Marafioti T., Salgado R., Le Quesne J., Nicholson A. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Castignani C., Bailey C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Kassiotis G., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., McGranahan N., Swanton C., and Jamal-Hanjani M.
Abstract: Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and ‘tumor spread through air spaces’ were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk.
Published: 2023

5. Genomic–transcriptomic evolution in lung cancer and metastasis

Author: Martinez-Ruiz, C, Black, J, Puttick, C, Hill, M, Demeulemeester, J, Larose Cadieux, E, Thol, K, Jones, T, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Prymas, P, Rowan, A, Ward, S, Cubitt, L, Athanasopoulou, F, Pich, O, Karasaki, T, Moore, D, Salgado, R, Colliver, E, Castignani, C, Dietzen, M, Huebner, A, Al Bakir, M, Tanic, M, Watkins, T, Lim, E, Al-Rashed, A, Lang, D, Clements, J, Cook, D, Rosenthal, R, Wilson, G, Frankell, A, de Carne Trecesson, S, East, P, Kanu, N, Litchfield, K, Birkbak, N, Hackshaw, A, Beck, S, Van Loo, P, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Bakir, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Karamani, A, Chain, B, Campbell, B, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Martinez-Ruiz C., Black J. R. M., Puttick C., Hill M. S., Demeulemeester J., Larose Cadieux E., Thol K., Jones T. P., Veeriah S., Naceur-Lombardelli C., Toncheva A., Prymas P., Rowan A., Ward S., Cubitt L., Athanasopoulou F., Pich O., Karasaki T., Moore D. A., Salgado R., Colliver E., Castignani C., Dietzen M., Huebner A., Al Bakir M., Tanic M., Watkins T. B. K., Lim E. L., Al-Rashed A. M., Lang D., Clements J., Cook D. E., Rosenthal R., Wilson G. A., Frankell A. M., de Carne Trecesson S., East P., Kanu N., Litchfield K., Birkbak N. J., Hackshaw A., Beck S., Van Loo P., Jamal-Hanjani M., McGranahan N., Swanton C., Bakir M. A., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Karamani A., Chain B., Campbell B. B., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Martinez-Ruiz, C, Black, J, Puttick, C, Hill, M, Demeulemeester, J, Larose Cadieux, E, Thol, K, Jones, T, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Prymas, P, Rowan, A, Ward, S, Cubitt, L, Athanasopoulou, F, Pich, O, Karasaki, T, Moore, D, Salgado, R, Colliver, E, Castignani, C, Dietzen, M, Huebner, A, Al Bakir, M, Tanic, M, Watkins, T, Lim, E, Al-Rashed, A, Lang, D, Clements, J, Cook, D, Rosenthal, R, Wilson, G, Frankell, A, de Carne Trecesson, S, East, P, Kanu, N, Litchfield, K, Birkbak, N, Hackshaw, A, Beck, S, Van Loo, P, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Bakir, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Karamani, A, Chain, B, Campbell, B, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Martinez-Ruiz C., Black J. R. M., Puttick C., Hill M. S., Demeulemeester J., Larose Cadieux E., Thol K., Jones T. P., Veeriah S., Naceur-Lombardelli C., Toncheva A., Prymas P., Rowan A., Ward S., Cubitt L., Athanasopoulou F., Pich O., Karasaki T., Moore D. A., Salgado R., Colliver E., Castignani C., Dietzen M., Huebner A., Al Bakir M., Tanic M., Watkins T. B. K., Lim E. L., Al-Rashed A. M., Lang D., Clements J., Cook D. E., Rosenthal R., Wilson G. A., Frankell A. M., de Carne Trecesson S., East P., Kanu N., Litchfield K., Birkbak N. J., Hackshaw A., Beck S., Van Loo P., Jamal-Hanjani M., McGranahan N., Swanton C., Bakir M. A., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Karamani A., Chain B., Campbell B. B., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., and Thomas M.
Abstract: Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis.
Published: 2023

6. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Author: Abbosh, C, Frankell, A, Harrison, T, Kisistok, J, Garnett, A, Johnson, L, Veeriah, S, Moreau, M, Chesh, A, Chaunzwa, T, Weiss, J, Schroeder, M, Ward, S, Grigoriadis, K, Shahpurwalla, A, Litchfield, K, Puttick, C, Biswas, D, Karasaki, T, Black, J, Martinez-Ruiz, C, Bakir, M, Pich, O, Watkins, T, Lim, E, Huebner, A, Moore, D, Godin-Heymann, N, L'Hernault, A, Bye, H, Odell, A, Roberts, P, Gomes, F, Patel, A, Manzano, E, Hiley, C, Carey, N, Riley, J, Cook, D, Hodgson, D, Stetson, D, Barrett, J, Kortlever, R, Evan, G, Hackshaw, A, Daber, R, Shaw, J, Aerts, H, Licon, A, Stahl, J, Jamal-Hanjani, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Birkbak, N, Mcgranahan, N, Swanton, C, Abbosh C., Frankell A. M., Harrison T., Kisistok J., Garnett A., Johnson L., Veeriah S., Moreau M., Chesh A., Chaunzwa T. L., Weiss J., Schroeder M. R., Ward S., Grigoriadis K., Shahpurwalla A., Litchfield K., Puttick C., Biswas D., Karasaki T., Black J. R. M., Martinez-Ruiz C., Bakir M. A., Pich O., Watkins T. B. K., Lim E. L., Huebner A., Moore D. A., Godin-Heymann N., L'Hernault A., Bye H., Odell A., Roberts P., Gomes F., Patel A. J., Manzano E., Hiley C. T., Carey N., Riley J., Cook D. E., Hodgson D., Stetson D., Barrett J. C., Kortlever R. M., Evan G. I., Hackshaw A., Daber R. D., Shaw J. A., Aerts H. J. W. L., Licon A., Stahl J., Jamal-Hanjani M., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Toncheva A., Chain B., Campbell B. B., Castignani C., Bailey C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Birkbak N. J., McGranahan N., Swanton C., Abbosh, C, Frankell, A, Harrison, T, Kisistok, J, Garnett, A, Johnson, L, Veeriah, S, Moreau, M, Chesh, A, Chaunzwa, T, Weiss, J, Schroeder, M, Ward, S, Grigoriadis, K, Shahpurwalla, A, Litchfield, K, Puttick, C, Biswas, D, Karasaki, T, Black, J, Martinez-Ruiz, C, Bakir, M, Pich, O, Watkins, T, Lim, E, Huebner, A, Moore, D, Godin-Heymann, N, L'Hernault, A, Bye, H, Odell, A, Roberts, P, Gomes, F, Patel, A, Manzano, E, Hiley, C, Carey, N, Riley, J, Cook, D, Hodgson, D, Stetson, D, Barrett, J, Kortlever, R, Evan, G, Hackshaw, A, Daber, R, Shaw, J, Aerts, H, Licon, A, Stahl, J, Jamal-Hanjani, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Birkbak, N, Mcgranahan, N, Swanton, C, Abbosh C., Frankell A. M., Harrison T., Kisistok J., Garnett A., Johnson L., Veeriah S., Moreau M., Chesh A., Chaunzwa T. L., Weiss J., Schroeder M. R., Ward S., Grigoriadis K., Shahpurwalla A., Litchfield K., Puttick C., Biswas D., Karasaki T., Black J. R. M., Martinez-Ruiz C., Bakir M. A., Pich O., Watkins T. B. K., Lim E. L., Huebner A., Moore D. A., Godin-Heymann N., L'Hernault A., Bye H., Odell A., Roberts P., Gomes F., Patel A. J., Manzano E., Hiley C. T., Carey N., Riley J., Cook D. E., Hodgson D., Stetson D., Barrett J. C., Kortlever R. M., Evan G. I., Hackshaw A., Daber R. D., Shaw J. A., Aerts H. J. W. L., Licon A., Stahl J., Jamal-Hanjani M., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Toncheva A., Chain B., Campbell B. B., Castignani C., Bailey C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Birkbak N. J., McGranahan N., and Swanton C.
Abstract: Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.
Published: 2023

7. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Author: Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., Kassiotis G., Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., and Kassiotis G.
Abstract: B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.
Published: 2023

8. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author: Frankell, A, Dietzen, M, Al Bakir, M, Lim, E, Karasaki, T, Ward, S, Veeriah, S, Colliver, E, Huebner, A, Bunkum, A, Hill, M, Grigoriadis, K, Moore, D, Black, J, Liu, W, Thol, K, Pich, O, Watkins, T, Naceur-Lombardelli, C, Cook, D, Salgado, R, Wilson, G, Bailey, C, Angelova, M, Bentham, R, Martinez-Ruiz, C, Abbosh, C, Nicholson, A, Le Quesne, J, Biswas, D, Rosenthal, R, Puttick, C, Hessey, S, Lee, C, Prymas, P, Toncheva, A, Smith, J, Xing, W, Nicod, J, Price, G, Kerr, K, Naidu, B, Middleton, G, Blyth, K, Fennell, D, Forster, M, Lee, S, Falzon, M, Hewish, M, Shackcloth, M, Benafif, S, Russell, P, Boleti, E, Krebs, M, Lester, J, Papadatos-Pastos, D, Ahmad, T, Thakrar, R, Lawrence, D, Navani, N, Janes, S, Dive, C, Blackhall, F, Summers, Y, Cave, J, Marafioti, T, Herrero, J, Quezada, S, Peggs, K, Schwarz, R, Van Loo, P, Miedema, D, Birkbak, N, Hiley, C, Hackshaw, A, Zaccaria, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Gilbert, K, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Aerts, H, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Demeulemeester, J, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Rane, J, Lam, J, Hartley, J, Enfield, K, Selvaraju, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Borg, E, Wilson, J, Procter, A, Ahmed, A, Taylor, M, Nair, A, Patrini, D, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Danson, S, Robinson, L, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Frankell A. M., Dietzen M., Al Bakir M., Lim E. L., Karasaki T., Ward S., Veeriah S., Colliver E., Huebner A., Bunkum A., Hill M. S., Grigoriadis K., Moore D. A., Black J. R. M., Liu W. K., Thol K., Pich O., Watkins T. B. K., Naceur-Lombardelli C., Cook D. E., Salgado R., Wilson G. A., Bailey C., Angelova M., Bentham R., Martinez-Ruiz C., Abbosh C., Nicholson A. G., Le Quesne J., Biswas D., Rosenthal R., Puttick C., Hessey S., Lee C., Prymas P., Toncheva A., Smith J., Xing W., Nicod J., Price G., Kerr K. M., Naidu B., Middleton G., Blyth K. G., Fennell D. A., Forster M. D., Lee S. M., Falzon M., Hewish M., Shackcloth M. J., Lim E., Benafif S., Russell P., Boleti E., Krebs M. G., Lester J. F., Papadatos-Pastos D., Ahmad T., Thakrar R. M., Lawrence D., Navani N., Janes S. M., Dive C., Blackhall F. H., Summers Y., Cave J., Marafioti T., Herrero J., Quezada S. A., Peggs K. S., Schwarz R. F., Van Loo P., Miedema D. M., Birkbak N. J., Hiley C. T., Hackshaw A., Zaccaria S., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Cheyne H., Khalil M., Richardson S., Cruickshank T., Gilbert K., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Aerts H. J. W. L., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Demeulemeester J., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Rane J. K., Lam J. M., Hartley J. A., Enfield K. S. S., Selvaraju K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Leung M., Escudero M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Borg E., Wilson J., Procter A. J., Ahmed A., Taylor M. N., Nair A., Patrini D., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Scarlett L., Richards J., Ingram P., Austin S., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Danson S., Robinson L., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., McGranahan N., Swanton C., Frankell, A, Dietzen, M, Al Bakir, M, Lim, E, Karasaki, T, Ward, S, Veeriah, S, Colliver, E, Huebner, A, Bunkum, A, Hill, M, Grigoriadis, K, Moore, D, Black, J, Liu, W, Thol, K, Pich, O, Watkins, T, Naceur-Lombardelli, C, Cook, D, Salgado, R, Wilson, G, Bailey, C, Angelova, M, Bentham, R, Martinez-Ruiz, C, Abbosh, C, Nicholson, A, Le Quesne, J, Biswas, D, Rosenthal, R, Puttick, C, Hessey, S, Lee, C, Prymas, P, Toncheva, A, Smith, J, Xing, W, Nicod, J, Price, G, Kerr, K, Naidu, B, Middleton, G, Blyth, K, Fennell, D, Forster, M, Lee, S, Falzon, M, Hewish, M, Shackcloth, M, Benafif, S, Russell, P, Boleti, E, Krebs, M, Lester, J, Papadatos-Pastos, D, Ahmad, T, Thakrar, R, Lawrence, D, Navani, N, Janes, S, Dive, C, Blackhall, F, Summers, Y, Cave, J, Marafioti, T, Herrero, J, Quezada, S, Peggs, K, Schwarz, R, Van Loo, P, Miedema, D, Birkbak, N, Hiley, C, Hackshaw, A, Zaccaria, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Gilbert, K, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Aerts, H, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Demeulemeester, J, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Rane, J, Lam, J, Hartley, J, Enfield, K, Selvaraju, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Borg, E, Wilson, J, Procter, A, Ahmed, A, Taylor, M, Nair, A, Patrini, D, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Danson, S, Robinson, L, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Frankell A. M., Dietzen M., Al Bakir M., Lim E. L., Karasaki T., Ward S., Veeriah S., Colliver E., Huebner A., Bunkum A., Hill M. S., Grigoriadis K., Moore D. A., Black J. R. M., Liu W. K., Thol K., Pich O., Watkins T. B. K., Naceur-Lombardelli C., Cook D. E., Salgado R., Wilson G. A., Bailey C., Angelova M., Bentham R., Martinez-Ruiz C., Abbosh C., Nicholson A. G., Le Quesne J., Biswas D., Rosenthal R., Puttick C., Hessey S., Lee C., Prymas P., Toncheva A., Smith J., Xing W., Nicod J., Price G., Kerr K. M., Naidu B., Middleton G., Blyth K. G., Fennell D. A., Forster M. D., Lee S. M., Falzon M., Hewish M., Shackcloth M. J., Lim E., Benafif S., Russell P., Boleti E., Krebs M. G., Lester J. F., Papadatos-Pastos D., Ahmad T., Thakrar R. M., Lawrence D., Navani N., Janes S. M., Dive C., Blackhall F. H., Summers Y., Cave J., Marafioti T., Herrero J., Quezada S. A., Peggs K. S., Schwarz R. F., Van Loo P., Miedema D. M., Birkbak N. J., Hiley C. T., Hackshaw A., Zaccaria S., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Cheyne H., Khalil M., Richardson S., Cruickshank T., Gilbert K., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Aerts H. J. W. L., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Demeulemeester J., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Rane J. K., Lam J. M., Hartley J. A., Enfield K. S. S., Selvaraju K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Leung M., Escudero M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Borg E., Wilson J., Procter A. J., Ahmed A., Taylor M. N., Nair A., Patrini D., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Scarlett L., Richards J., Ingram P., Austin S., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Danson S., Robinson L., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., McGranahan N., and Swanton C.
Abstract: Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.
Published: 2023

9. SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2

Author: Eales, O, Page, AJ, de Oliveira Martins, L, Wang, H, Bodinier, B, Haw, D, Jonnerby, J, Atchison, C, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Nunez, RTM, Bonsall, D, Rambaut, A, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Chapman, MHS, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O’Toole, Á, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N - F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Cox, MG, Abudahab, K, Menegazzo, M, MEng, BEWT, Yeats, CA, Mukaddas, A, Wright, DW, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J - P, Curran, T, Morgan, S, Maxwell, P, Smith, K, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Stanley, R, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L - A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea-Medina, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, Bouzidi, KE, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O’Brien, PS, Rushton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, Whitwham, A, Ashby, D, Barclay, W, Taylor, G, Cooke, G, Ward, H, Darzi, A, Riley, S, Chadeau-Hyam, M, Donnelly, CA, Elliott, P, The COVID-19 Genomics UK (COG-UK) Consortium, Department of Health, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), Cancer Research UK, Commission of the European Communities, Wellcome Trust, National Institute for Health Research, and Imperial College Healthcare NHS Trust: Research Capability Funding (RCF)
Subjects: Delta variant, Science & Technology, SARS-CoV-2, COVID-19, 1103 Clinical Sciences, C500, Microbiology, Genetic diversity, B900, Infectious Diseases, England, COVID-19 Genomics UK (COG-UK) Consortium, 1108 Medical Microbiology, Mutation, Humans, Transmission advantage, Life Sciences & Biomedicine, Phylogeny, 0605 Microbiology
Abstract: Background Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.
Published: 2022

10. SARS-CoV-2 evolution during treatment of chronic infection

Author: Kemp, S. A., Collier, D. A., Datir, R. P., Ferreira, I. A. T. M., Gayed, S., Jahun, A., Hosmillo, M., Rees-Spear, C., Mlcochova, P., Lumb, I. U., Roberts, D. J., Chandra, A., Temperton, N., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Estee Torok, M., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Abnizova, I., Aigrain, L., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Betteridge, E., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Bonfield, J., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Goodwin, S., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Liddle, J., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Makunin, A., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mccarthy, S., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Puethe, C., Quail, M., Rajan, D., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Scott, C., Seekings, P., Shirley, L., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Jansen Van, P., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Whitwham, A., Widaa, S., Williams, M., Wilson, M., Wright, S., Farr, B. W., Quail, M. A., Thurston, S. A. J., Bronner, I. F., Redshaw, N. M., Lensing, S. V., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Sharrocks, K., Blane, E., Modis, Y., Leigh, K. E., Briggs, J. A. G., van Gils, M. J., Smith, K. G. C., Bradley, J. R., Doffinger, R., Ceron-Gutierrez, L., Barcenas-Morales, G., Pollock, D. D., Goldstein, R. A., Smielewska, A., Skittrall, J. P., Gouliouris, T., Goodfellow, I. G., Gkrania-Klotsas, E., Illingworth, C. J. R., Mccoy, L. E., Gupta, R. K., Medical Microbiology and Infection Prevention, AII - Infectious diseases, Collier, Dami A [0000-0001-5446-4423], Jahun, Aminu [0000-0002-4585-1701], Temperton, Nigel [0000-0002-7978-3815], Modis, Yorgo [0000-0002-6084-0429], Briggs, John AG [0000-0003-3990-6910], Goldstein, Richard A [0000-0001-5148-4672], Skittrall, Jordan P [0000-0002-8228-3758], Gkrania-Klotsas, Effrossyni [0000-0002-0930-8330], McCoy, Laura E [0000-0001-9503-7946], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Time Factors, viruses, Passive, Antibodies, Viral, CITIID-NIHR BioResource COVID-19 Collaboration, 2.1 Biological and endogenous factors, Viral, Aetiology, Neutralizing, Lung, Phylogeny, neutralising antibodies, Infectivity, education.field_of_study, Genome, Multidisciplinary, Alanine, biology, High-Throughput Nucleotide Sequencing, Viral Load, Spike Glycoprotein, Virus Shedding, Adenosine Monophosphate, Aged, Antibodies, Neutralizing, COVID-19, Chronic Disease, Genome, Viral, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Mutagenesis, Mutant Proteins, Mutation, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Evolution, Molecular, Infectious Diseases, Pneumonia & Influenza, Antibody, Infection, Viral load, Biotechnology, Evolution, General Science & Technology, antibody escape, Convalescent plasma, 030106 microbiology, Population, evasion, Antibodies, Virus, Article, Vaccine Related, resistance, 03 medical and health sciences, Immune system, COVID-19 Genomics UK (COG-UK) Consortium, Biodefense, Genetics, Viral shedding, education, COVID-19 Serotherapy, QR355, Prevention, Wild type, Molecular, Pneumonia, Virology, COVID-19 Drug Treatment, Coronavirus, Emerging Infectious Diseases, Good Health and Well Being, 030104 developmental biology, biology.protein, Immunization, immune suppression, mutation
Abstract: The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.
Published: 2021

11. P1460: SAFETY AND EFFICACY FINDINGS OF AUTO1, A FAST-OFF RATE CD19 CAR, IN RELAPSED/REFRACTORY PRIMARY CNS LYMPHOMA

Author: Roddie, C., primary, Dias, J., additional, O’Reilly, M., additional, Green, L., additional, Vaughan, M., additional, Agliardi, G., additional, Garcia, J., additional, Lewin, E., additional, Lowdell, M., additional, Mitsikakou, M., additional, Charalambous, E., additional, Hotblack, A., additional, Dreau, H., additional, Marzolini, M., additional, Wood, L., additional, Every-Clayton, C., additional, Lal, A., additional, Ngai, Y., additional, Popova, B., additional, Malhi, A., additional, Kunaseelan, S., additional, Spanswick, V., additional, Lowe, H., additional, Ensell, L., additional, Hartley, J., additional, Domning, S., additional, Thorne, L., additional, Hyare, H., additional, Murphy, P., additional, Linch, D., additional, Fox, C., additional, Peggs, K., additional, Cwynarski, K., additional, and Pule, M., additional
Published: 2022
Full Text: View/download PDF

12. P1459: SAFETY AND EFFICACY FINDINGS OF AUTO1, A FAST-OFF RATE CD19 CAR, IN RELAPSED/REFRACTORY B-CELL NON-HODGKIN’S LYMPHOMA (B-NHL), AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) / SMALL LYMPHOCYTIC LYMPHOMA (SLL)

Author: Roddie, C., primary, Dias, J., additional, O’Reilly, M., additional, Mitsikakou, M., additional, Charalambous, E., additional, Green, L., additional, Vaughan, M., additional, Agliardi, G., additional, Garcia, J., additional, Lewin, E., additional, Lowdell, M., additional, Marzolini, M., additional, Wood, L., additional, Holmes, H., additional, Ngai, Y., additional, Popova, B., additional, Wilson, W., additional, Kunaseelan, S., additional, Spanswick, V., additional, Lowe, H., additional, Ensell, L., additional, Hartley, J., additional, Domning, S., additional, Morley, S., additional, Marafioti, T., additional, Bloor, A., additional, Irvine, D., additional, Orchard, K., additional, Khwaja, A., additional, Linch, D., additional, Pule, M., additional, and Peggs, K., additional
Published: 2022
Full Text: View/download PDF

13. Genomic reconstruction of the SARS-CoV-2 epidemic in England

Author: Vöhringer, HS, Sanderson, T, Sinnott, M, De Maio, N, Nguyen, T, Goater, R, Schwach, F, Harrison, I, Hellewell, J, Ariani, CV, Gonçalves, S, Jackson, DK, Johnston, I, Jung, AW, Saint, C, Sillitoe, J, Suciu, M, Goldman, N, Panovska-Griffiths, J, Abnizova, I, Aigrain, L, Alderton, A, Ali, M, Allen, L, Amato, R, Anderson, R, Ariani, C, Austin-Guest, S, Bala, S, Barrett, J, Bassett, A, Battleday, K, Beal, J, Beale, M, Beaver, C, Bellany, S, Bellerby, T, Bellis, K, Berger, D, Berriman, M, Betteridge, E, Bevan, P, Binley, S, Bishop, J, Blackburn, K, Bonfield, J, Boughton, N, Bowker, S, Brendler-Spaeth, T, Bronner, I, Brooklyn, T, Buddenborg, SK, Bush, R, Caetano, C, Cagan, A, Carter, N, Cartwright, J, Monteiro, TC, Chapman, L, Chillingworth, T-J, Clapham, P, Clark, R, Clarke, A, Clarke, C, Cole, D, Cook, E, Coppola, M, Cornell, L, Cornwell, C, Corton, C, Crackett, A, Cranage, A, Craven, H, Craw, S, Crawford, M, Cutts, T, Dabrowska, M, Davies, M, Davies, R, Dawson, J, Day, C, Densem, A, Dibling, T, Dockree, C, Dodd, D, Dogga, S, Dorman, M, Dougan, G, Dougherty, M, Dove, A, Drummond, L, Drury, E, Dudek, M, Durham, J, Durrant, L, Easthope, E, Eckert, S, Ellis, P, Farr, B, Fenton, M, Ferrero, M, Flack, N, Fordham, H, Forsythe, G, Foulser, L, Francis, M, Fraser, A, Freeman, A, Galvin, A, Garcia-Casado, M, Gedny, A, Girgis, S, Glover, J, Goncalves, S, Goodwin, S, Gould, O, Gourtovaia, M, Gray, A, Gray, E, Griffiths, C, Gu, Y, Guerin, F, Hamilton, W, Hanks, H, Harrison, E, Harrott, A, Harry, E, Harvison, J, Heath, P, Hernandez-Koutoucheva, A, Hobbs, R, Holland, D, Holmes, S, Hornett, G, Hough, N, Huckle, L, Hughes-Hallet, L, Hunter, A, Inglis, S, Iqbal, S, Jackson, A, Jackson, D, James, K, Jamrozy, D, Verdejo, CJ, Jones, M, Kallepally, K, Kane, L, Kay, K, Kay, S, Keatley, J, Keith, A, King, A, Kitchin, L, Kleanthous, M, Klimekova, M, Korlevic, P, Krasheninnkova, K, Lane, G, Langford, C, Laverack, A, Law, K, Lawniczak, M, Lensing, S, Leonard, S, Letchford, L, Lewis, K, Lewis-Wade, A, Liddle, J, Lin, Q, Lindsay, S, Linsdell, S, Livett, R, Lo, S, Long, R, Lovell, J, Ludden, C, Mack, J, Maddison, M, Makunin, A, Mamun, I, Mansfield, J, Marriott, N, Martin, M, Mayho, M, McCarthy, S, McClintock, J, McGuigan, S, McHugh, S, McMinn, L, Meadows, C, Mobley, E, Moll, R, Morra, M, Morrow, L, Murie, K, Nash, S, Nathwani, C, Naydenova, P, Neaverson, A, Nelson, R, Nerou, E, Nicholson, J, Nimz, T, Noell, GG, O’Meara, S, Ohan, V, Oliver, K, Olney, C, Ormond, D, Oszlanczi, A, Palmer, S, Pang, YF, Pardubska, B, Park, N, Parmar, A, Patel, G, Patel, M, Payne, M, Peacock, S, Petersen, A, Plowman, D, Preston, T, Prestwood, L, Puethe, C, Quail, M, Rajan, D, Rajatileka, S, Rance, R, Rawlings, S, Redshaw, N, Reynolds, J, Reynolds, M, Rice, S, Richardson, M, Roberts, C, Robinson, K, Robinson, M, Robinson, D, Rogers, H, Rojo, EM, Roopra, D, Rose, M, Rudd, L, Sadri, R, Salmon, N, Saul, D, Scott, C, Seekings, P, Shirley, L, Simms, A, Sivadasan, S, Siwek, B, Sizer, D, Skeldon, K, Skelton, J, Slater-Tunstill, J, Sloper, L, Smerdon, N, Smith, C, Smith, J, Smith, K, Smith, M, Smith, S, Smith, T, Sneade, L, Soria, CD, Sousa, C, Souster, E, Sparkes, A, Spencer-Chapman, M, Squares, J, Stanley, R, Steed, C, Stickland, T, Still, I, Stratton, MR, Strickland, M, Swann, A, Swiatkowska, A, Sycamore, N, Swift, E, Symons, E, Szluha, S, Taluy, E, Tao, N, Taylor, K, Taylor, S, Thompson, S, Thompson, M, Thomson, M, Thomson, N, Thurston, S, Tonkin-Hill, G, Toombs, D, Topping, B, Tovar-Corona, J, Ungureanu, D, Uphill, J, Urbanova, J, Van Vuuren, PJ, Vancollie, V, Voak, P, Walker, D, Walker, M, Waller, M, Ward, G, Weatherhogg, C, Webb, N, Weldon, D, Wells, A, Wells, E, Westwood, L, Whipp, T, Whiteley, T, Whitton, G, Whitwham, A, Widaa, S, Williams, M, Wilson, M, Wright, S, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, A, Snell, LB, Corden, S, Nastouli, E, Nebbia, G, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Smith, DL, Aanensen, DM, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Page, AJ, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O’Toole, Á, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N-F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Bellis, KL, Dorman, MJ, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, Tovar-Corona, JM, Cox, M, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J-P, Curran, T, Morgan, S, Maxwell, P, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L-A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Afifi, S, Beer, R, Maksimovic, J, Masters, KM, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O’Brien, S, Rushton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Bronner, IF, Farr, BW, Lensing, SV, McCarthy, SA, Quail, MA, Redshaw, NM, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Birney, E, Volz, E, Funk, S, Martincorena, I, Barrett, JC, and Gerstung, M
Abstract: The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.
Published: 2021

14. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

Author: Collier, D. A., De Marco, A., Ferreira, I. A. T. M., Meng, B., Datir, R. P., Walls, A. C., Kemp, S. A., Bassi, J., Pinto, D., Silacci-Fregni, C., Bianchi, S., Tortorici, M. A., Bowen, J., Culap, K., Jaconi, S., Cameroni, E., Snell, G., Pizzuto, M. S., Pellanda, A. F., Garzoni, C., Riva, A., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Mccoy, L. E., Smith, K. G. C., Bradley, J. R., Temperton, N., Ceron-Gutierrez, L., Barcenas-Morales, G., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Torok, M. E., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., Hosmillo, M., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Betteridge, E., Farr, B. W., Goodwin, S., Quail, M. A., Scott, C., Shirley, L., Thurston, S. A. J., Rajan, D., Bronner, I. F., Aigrain, L., Redshaw, N. M., Lensing, S. V., Mccarthy, S., Makunin, A., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Bonfield, J., Puethe, C., Whitwham, A., Liddle, J., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Abnizova, I., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Quail, M., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Seekings, P., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Van, P. J., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Widaa, S., Williams, M., Wilson, M., Wright, S., Harvey, W., Virgin, H. W., Lanzavecchia, A., Piccoli, L., Doffinger, R., Wills, M., Veesler, D., Corti, D., and Gupta, R. K.
Subjects: 0301 basic medicine, Male, Models, Molecular, Passive, Antibodies, Viral, Neutralization, 0302 clinical medicine, Models, Monoclonal, 80 and over, Viral, Neutralizing antibody, Neutralizing, Aged, 80 and over, Vaccines, Vaccines, Synthetic, Multidisciplinary, biology, Antibodies, Monoclonal, C500, Middle Aged, C700, Spike Glycoprotein, Vaccination, Spike Glycoprotein, Coronavirus, Female, Angiotensin-Converting Enzyme 2, Antibody, Aged, Antibodies, Neutralizing, COVID-19, COVID-19 Vaccines, HEK293 Cells, Humans, Immune Evasion, Immunization, Passive, Mutation, Neutralization Tests, SARS-CoV-2, medicine.drug_class, B100, Monoclonal antibody, Antibodies, Virus, 03 medical and health sciences, Immune system, medicine, COVID-19 Serotherapy, QR355, Synthetic, Molecular, Virology, Coronavirus, 030104 developmental biology, Immunization, biology.protein, 030217 neurology & neurosurgery
Abstract: Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.
Published: 2021

15. 922P EACH: A phase II study evaluating the safety and anti-tumour activity of avelumab and cetuximab in recurrent/metastatic squamous cell carcinomas

Author: Forster, M., primary, Metcalf, R., additional, Sacco, J., additional, Kong, A., additional, Wheeler, G., additional, Forsyth, S., additional, Bhat, R., additional, Blair, K., additional, Ward, J., additional, Lowe, H., additional, Spanswick, V., additional, Ensell, L., additional, Hartley, J., additional, and White, L., additional
Published: 2020
Full Text: View/download PDF

16. A comparison of CellCollector with CellSearch in patients with neuroendocrine tumours

Author: Mandair, D, primary, Vesely, C, additional, Ensell, L, additional, Lowe, H, additional, Spanswick, V, additional, Hartley, J A, additional, Caplin, M E, additional, and Meyer, T, additional
Published: 2016
Full Text: View/download PDF

17. 2389 Detection of SSTR2 and 5 expression in circulating tumour cells from patients with neuroendocrine tumours

Author: Childs, A., primary, Vesely, C., additional, Ensell, L., additional, Caplin, M., additional, Toumpanakis, C., additional, Thirlwell, C., additional, Hartley, J., additional, and Meyer, T., additional
Published: 2015
Full Text: View/download PDF

18. Genomic reconstruction of the SARS-CoV-2 epidemic in England

Author: Vöhringer, HS, Sanderson, T, Sinnott, M, De Maio, N, Nguyen, T, Goater, R, Schwach, F, Harrison, I, Hellewell, J, Ariani, CV, Gonçalves, S, Jackson, DK, Johnston, I, Jung, AW, Saint, C, Sillitoe, J, Suciu, M, Goldman, N, Panovska-Griffiths, J, Abnizova, I, Aigrain, L, Alderton, A, Ali, M, Allen, L, Amato, R, Anderson, R, Ariani, C, Austin-Guest, S, Bala, S, Barrett, J, Bassett, A, Battleday, K, Beal, J, Beale, M, Beaver, C, Bellany, S, Bellerby, T, Bellis, K, Berger, D, Berriman, M, Betteridge, E, Bevan, P, Binley, S, Bishop, J, Blackburn, K, Bonfield, J, Boughton, N, Bowker, S, Brendler-Spaeth, T, Bronner, I, Brooklyn, T, Buddenborg, SK, Bush, R, Caetano, C, Cagan, A, Carter, N, Cartwright, J, Monteiro, TC, Chapman, L, Chillingworth, TJ, Clapham, P, Clark, R, Clarke, A, Clarke, C, Cole, D, Cook, E, Coppola, M, Cornell, L, Cornwell, C, Corton, C, Crackett, A, Cranage, A, Craven, H, Craw, S, Crawford, M, Cutts, T, Dabrowska, M, Davies, M, Davies, R, Dawson, J, Day, C, Densem, A, Dibling, T, Dockree, C, Dodd, D, Dogga, S, Dorman, M, Dougan, G, Dougherty, M, Dove, A, Drummond, L, Drury, E, Dudek, M, Durham, J, Durrant, L, Easthope, E, Eckert, S, Ellis, P, Farr, B, Fenton, M, Ferrero, M, Flack, N, Fordham, H, Forsythe, G, Foulser, L, Francis, M, Fraser, A, Freeman, A, Galvin, A, Garcia-Casado, M, Gedny, A, Girgis, S, Glover, J, Goncalves, S, Goodwin, S, Gould, O, Gourtovaia, M, Gray, A, Gray, E, Griffiths, C, Gu, Y, Guerin, F, Hamilton, W, Hanks, H, Harrison, E, Harrott, A, Harry, E, Harvison, J, Heath, P, Hernandez-Koutoucheva, A, Hobbs, R, Holland, D, Holmes, S, Hornett, G, Hough, N, Huckle, L, Hughes-Hallet, L, Hunter, A, Inglis, S, Iqbal, S, Jackson, A, Jackson, D, James, K, Jamrozy, D, Verdejo, CJ, Jones, M, Kallepally, K, Kane, L, Kay, K, Kay, S, Keatley, J, Keith, A, King, A, Kitchin, L, Kleanthous, M, Klimekova, M, Korlevic, P, Krasheninnkova, K, Lane, G, Langford, C, Laverack, A, Law, K, Lawniczak, M, Lensing, S, Leonard, S, Letchford, L, Lewis, K, Lewis-Wade, A, Liddle, J, Lin, Q, Lindsay, S, Linsdell, S, Livett, R, Lo, S, Long, R, Lovell, J, Ludden, C, Mack, J, Maddison, M, Makunin, A, Mamun, I, Mansfield, J, Marriott, N, Martin, M, Mayho, M, McCarthy, S, McClintock, J, McGuigan, S, McHugh, S, McMinn, L, Meadows, C, Mobley, E, Moll, R, Morra, M, Morrow, L, Murie, K, Nash, S, Nathwani, C, Naydenova, P, Neaverson, A, Nelson, R, Nerou, E, Nicholson, J, Nimz, T, Noell, GG, O’Meara, S, Ohan, V, Oliver, K, Olney, C, Ormond, D, Oszlanczi, A, Palmer, S, Pang, YF, Pardubska, B, Park, N, Parmar, A, Patel, G, Patel, M, Payne, M, Peacock, S, Petersen, A, Plowman, D, Preston, T, Prestwood, L, Puethe, C, Quail, M, Rajan, D, Rajatileka, S, Rance, R, Rawlings, S, Redshaw, N, Reynolds, J, Reynolds, M, Rice, S, Richardson, M, Roberts, C, Robinson, K, Robinson, M, Robinson, D, Rogers, H, Rojo, EM, Roopra, D, Rose, M, Rudd, L, Sadri, R, Salmon, N, Saul, D, Scott, C, Seekings, P, Shirley, L, Simms, A, Sivadasan, S, Siwek, B, Sizer, D, Skeldon, K, Skelton, J, Slater-Tunstill, J, Sloper, L, Smerdon, N, Smith, C, Smith, J, Smith, K, Smith, M, Smith, S, Smith, T, Sneade, L, Soria, CD, Sousa, C, Souster, E, Sparkes, A, Spencer-Chapman, M, Squares, J, Stanley, R, Steed, C, Stickland, T, Still, I, Stratton, MR, Strickland, M, Swann, A, Swiatkowska, A, Sycamore, N, Swift, E, Symons, E, Szluha, S, Taluy, E, Tao, N, Taylor, K, Taylor, S, Thompson, S, Thompson, M, Thomson, M, Thomson, N, Thurston, S, Tonkin-Hill, G, Toombs, D, Topping, B, Tovar-Corona, J, Ungureanu, D, Uphill, J, Urbanova, J, Van Vuuren, PJ, Vancollie, V, Voak, P, Walker, D, Walker, M, Waller, M, Ward, G, Weatherhogg, C, Webb, N, Weldon, D, Wells, A, Wells, E, Westwood, L, Whipp, T, Whiteley, T, Whitton, G, Whitwham, A, Widaa, S, Williams, M, Wilson, M, Wright, S, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, A, Snell, LB, Corden, S, Nastouli, E, Nebbia, G, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Smith, DL, Aanensen, DM, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Page, AJ, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O’Toole, Á, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, NF, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Bellis, KL, Dorman, MJ, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, Tovar-Corona, JM, Cox, MG, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, JP, Curran, T, Morgan, S, Maxwell, P, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, LA, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Afifi, S, Beer, R, Maksimovic, J, Masters, KMC, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O’Brien, S, Rushton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Bronner, IF, Farr, BW, Lensing, SV, McCarthy, SA, Quail, MA, Redshaw, NM, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Birney, E, Volz, E, Funk, S, Martincorena, I, Barrett, JC, Gerstung, M, Vöhringer, HS, Sanderson, T, Sinnott, M, De Maio, N, Nguyen, T, Goater, R, Schwach, F, Harrison, I, Hellewell, J, Ariani, CV, Gonçalves, S, Jackson, DK, Johnston, I, Jung, AW, Saint, C, Sillitoe, J, Suciu, M, Goldman, N, Panovska-Griffiths, J, Abnizova, I, Aigrain, L, Alderton, A, Ali, M, Allen, L, Amato, R, Anderson, R, Ariani, C, Austin-Guest, S, Bala, S, Barrett, J, Bassett, A, Battleday, K, Beal, J, Beale, M, Beaver, C, Bellany, S, Bellerby, T, Bellis, K, Berger, D, Berriman, M, Betteridge, E, Bevan, P, Binley, S, Bishop, J, Blackburn, K, Bonfield, J, Boughton, N, Bowker, S, Brendler-Spaeth, T, Bronner, I, Brooklyn, T, Buddenborg, SK, Bush, R, Caetano, C, Cagan, A, Carter, N, Cartwright, J, Monteiro, TC, Chapman, L, Chillingworth, TJ, Clapham, P, Clark, R, Clarke, A, Clarke, C, Cole, D, Cook, E, Coppola, M, Cornell, L, Cornwell, C, Corton, C, Crackett, A, Cranage, A, Craven, H, Craw, S, Crawford, M, Cutts, T, Dabrowska, M, Davies, M, Davies, R, Dawson, J, Day, C, Densem, A, Dibling, T, Dockree, C, Dodd, D, Dogga, S, Dorman, M, Dougan, G, Dougherty, M, Dove, A, Drummond, L, Drury, E, Dudek, M, Durham, J, Durrant, L, Easthope, E, Eckert, S, Ellis, P, Farr, B, Fenton, M, Ferrero, M, Flack, N, Fordham, H, Forsythe, G, Foulser, L, Francis, M, Fraser, A, Freeman, A, Galvin, A, Garcia-Casado, M, Gedny, A, Girgis, S, Glover, J, Goncalves, S, Goodwin, S, Gould, O, Gourtovaia, M, Gray, A, Gray, E, Griffiths, C, Gu, Y, Guerin, F, Hamilton, W, Hanks, H, Harrison, E, Harrott, A, Harry, E, Harvison, J, Heath, P, Hernandez-Koutoucheva, A, Hobbs, R, Holland, D, Holmes, S, Hornett, G, Hough, N, Huckle, L, Hughes-Hallet, L, Hunter, A, Inglis, S, Iqbal, S, Jackson, A, Jackson, D, James, K, Jamrozy, D, Verdejo, CJ, Jones, M, Kallepally, K, Kane, L, Kay, K, Kay, S, Keatley, J, Keith, A, King, A, Kitchin, L, Kleanthous, M, Klimekova, M, Korlevic, P, Krasheninnkova, K, Lane, G, Langford, C, Laverack, A, Law, K, Lawniczak, M, Lensing, S, Leonard, S, Letchford, L, Lewis, K, Lewis-Wade, A, Liddle, J, Lin, Q, Lindsay, S, Linsdell, S, Livett, R, Lo, S, Long, R, Lovell, J, Ludden, C, Mack, J, Maddison, M, Makunin, A, Mamun, I, Mansfield, J, Marriott, N, Martin, M, Mayho, M, McCarthy, S, McClintock, J, McGuigan, S, McHugh, S, McMinn, L, Meadows, C, Mobley, E, Moll, R, Morra, M, Morrow, L, Murie, K, Nash, S, Nathwani, C, Naydenova, P, Neaverson, A, Nelson, R, Nerou, E, Nicholson, J, Nimz, T, Noell, GG, O’Meara, S, Ohan, V, Oliver, K, Olney, C, Ormond, D, Oszlanczi, A, Palmer, S, Pang, YF, Pardubska, B, Park, N, Parmar, A, Patel, G, Patel, M, Payne, M, Peacock, S, Petersen, A, Plowman, D, Preston, T, Prestwood, L, Puethe, C, Quail, M, Rajan, D, Rajatileka, S, Rance, R, Rawlings, S, Redshaw, N, Reynolds, J, Reynolds, M, Rice, S, Richardson, M, Roberts, C, Robinson, K, Robinson, M, Robinson, D, Rogers, H, Rojo, EM, Roopra, D, Rose, M, Rudd, L, Sadri, R, Salmon, N, Saul, D, Scott, C, Seekings, P, Shirley, L, Simms, A, Sivadasan, S, Siwek, B, Sizer, D, Skeldon, K, Skelton, J, Slater-Tunstill, J, Sloper, L, Smerdon, N, Smith, C, Smith, J, Smith, K, Smith, M, Smith, S, Smith, T, Sneade, L, Soria, CD, Sousa, C, Souster, E, Sparkes, A, Spencer-Chapman, M, Squares, J, Stanley, R, Steed, C, Stickland, T, Still, I, Stratton, MR, Strickland, M, Swann, A, Swiatkowska, A, Sycamore, N, Swift, E, Symons, E, Szluha, S, Taluy, E, Tao, N, Taylor, K, Taylor, S, Thompson, S, Thompson, M, Thomson, M, Thomson, N, Thurston, S, Tonkin-Hill, G, Toombs, D, Topping, B, Tovar-Corona, J, Ungureanu, D, Uphill, J, Urbanova, J, Van Vuuren, PJ, Vancollie, V, Voak, P, Walker, D, Walker, M, Waller, M, Ward, G, Weatherhogg, C, Webb, N, Weldon, D, Wells, A, Wells, E, Westwood, L, Whipp, T, Whiteley, T, Whitton, G, Whitwham, A, Widaa, S, Williams, M, Wilson, M, Wright, S, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, A, Snell, LB, Corden, S, Nastouli, E, Nebbia, G, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Smith, DL, Aanensen, DM, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Page, AJ, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O’Toole, Á, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, NF, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Bellis, KL, Dorman, MJ, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, Tovar-Corona, JM, Cox, MG, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, JP, Curran, T, Morgan, S, Maxwell, P, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, LA, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Afifi, S, Beer, R, Maksimovic, J, Masters, KMC, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O’Brien, S, Rushton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Bronner, IF, Farr, BW, Lensing, SV, McCarthy, SA, Quail, MA, Redshaw, NM, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Birney, E, Volz, E, Funk, S, Martincorena, I, Barrett, JC, and Gerstung, M
Abstract: The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.

19. Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Author: Cotton, S, McHugh, MP, Dewar, R, Haas, JG, Templeton, K, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, A, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Cutino-Moguel, T, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Kele, B, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, Peacock, SJ, de Silva, TI, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Page, AJ, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O'Toole, Á, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Heyburn, D, Charalampous, T, Alcolea-Medina, A, Kitchman, K, McNal, A, Pritch, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, Anna, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson DipHe, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Cox, M, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J, Curran, T, Morgan, S, Maxwell, P, Smith, K, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Stanley, R, Idle, G, Bradley, DT, Killough, NF, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Delgado Callico, L, Fragakis, M, Galai, K, Jermy, A, Judges, S, Markov, A, McManus, GM, Smith, KS, Thomas-McEwen, PMD, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk Fd, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workma, T, Shelest, E, Debebe, J, Sang, F, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O'Brien, S, Rushton, S, Sanderson, R, Perkins, J, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrer, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, Whitwham, A, Cotton, S, McHugh, MP, Dewar, R, Haas, JG, Templeton, K, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, A, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Cutino-Moguel, T, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Kele, B, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, Peacock, SJ, de Silva, TI, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Page, AJ, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O'Toole, Á, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Heyburn, D, Charalampous, T, Alcolea-Medina, A, Kitchman, K, McNal, A, Pritch, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, Anna, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson DipHe, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Cox, M, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J, Curran, T, Morgan, S, Maxwell, P, Smith, K, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Stanley, R, Idle, G, Bradley, DT, Killough, NF, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Delgado Callico, L, Fragakis, M, Galai, K, Jermy, A, Judges, S, Markov, A, McManus, GM, Smith, KS, Thomas-McEwen, PMD, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk Fd, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workma, T, Shelest, E, Debebe, J, Sang, F, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O'Brien, S, Rushton, S, Sanderson, R, Perkins, J, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrer, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, and Whitwham, A
Abstract: Summary Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine.

20. Recurrent SARS-CoV-2 mutations in immunodeficient patients

Author: Wilkinson, S. A. J., Sparks, N., Kele, B., Peacock, T. P., Robson, S. C., Connor, T. R., Loman, N. J., Golubchik, T., Martinez Nunez, R. T., Bonsall, D., Rambaut, A., Snell, L. B., Livett, R., Ludden, C., Corden, S., Nastouli, E., Nebbia, G., Johnston, I., Lythgoe, K., Estee Torok, M., Goodfellow, I. G., Prieto, J. A., Saeed, K., Jackson, D. K., Houlihan, C., Frampton, D., Hamilton, W. L., Witney, A. A., Bucca, G., Pope, C. F., Moore, C., Thomson, E. C., Harrison, E. M., Smith, C. P., Rogan, F., Beckwith, S. M., Murray, A., Singleton, D., Eastick, K., Sheridan, L. A., Randell, P., Jackson, L. M., Ariani, C. V., Gonçalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Moses, S., Nicholls, S., Bull, M., Amato, R., Smith, D. L., Aanensen, D. M., Barrett, J. C., Aggarwal, D., Shepherd, J. G., Curran, M. D., Parmar, S., Parker, M. D., Williams, C., Glaysher, S., Underwood, A. P., Bashton, M., Pacchiarini, N., Loveson, K. F., Byott, M., Carabelli, A. M., Templeton, K. E., de Silva, T. I., Wang, D., Langford, C. F., Sillitoe, J., Gunson, R. N., Cottrell, S., O’Grady, J., Kwiatkowski, D., Lillie, P. J., Cortes, N., Moore, N., Thomas, C., Burns, P. J., Mahungu, T. W., Liggett, S., Beckett, A. H., Holden, M. T. G., Levett, L. J., Osman, H., Hassan-Ibrahim, M. O., Simpson, D. A., Chand, M., Gupta, R. K., Darby, A. C., Paterson, S., Pybus, O. G., Volz, E. M., de Angelis, D., Robertson, D. L., Page, A. J., Martincorena, I., Aigrain, L., Bassett, A. R., Wong, N., Taha, Y., Erkiert, M. J., Spencer Chapman, M. H., Dewar, R., McHugh, M. P., Mookerjee, S., Aplin, S., Harvey, M., Sass, T., Umpleby, H., Wheeler, H., McKenna, J. P., Warne, B., Taylor, J. F., Chaudhry, Y., Izuagbe, R., Jahun, A. S., Young, G. R., McMurray, C., McCann, C. M., Nelson, A., Elliott, S., Price, A., Crown, M. R., Rey, S, Roy, S., Temperton, B., Shaaban, S., Hesketh, A. R., Laing, K. G., Monahan, I. M., Heaney, J., Pelosi, E., Silviera, S., Wilson-Davies, E., Fryer, H., Adams, H., du Plessis, L., Johnson, R., Harvey, W. T., Hughes, J., Orton, R. J., Spurgin, L. G., Bourgeois, Y., Ruis, C., O’Toole, Á., Gourtovaia, M., Sanderson, T., Fraser, C., Edgeworth, J., Breuer, J., Michell, S. L., Todd, J. A., John, M., Buck, D., Gajee, K., Kay, G. L., Peacock, S. J., Heyburn, D., Kitchman, K., McNally, A., Pritchard, D. T., Dervisevic, S., Muir, P., Robinson, E., Vipond, B. B., Ramadan, N. A., Jeanes, C., Weldon, D., Catalan, J., Jones, N., da Silva Filipe, A., Fuchs, M., Miskelly, J., Jeffries, A. R., Oliver, K., Park, N. R., Ash, A., Koshy, C., Barrow, M., Buchan, S. L., Mantzouratou, A., Clark, G., Holmes, C. W., Campbell, S., Davis, T., Tan, N. K., Brown, J. R., Harris, K. A., Kidd, S. P., Grant, P. R., Xu-McCrae, L., Cox, A., Madona, P., Pond, M., Randell, P. A., Withell, K. T., Graham, C., Denton-Smith, R., Swindells, E., Turnbull, R., Sloan, T. J., Bosworth, A., Hutchings, S., Pymont, H. M., Casey, A., Ratcliffe, L., Jones, C. R., Knight, B. A., Haque, T., Hart, J., Irish-Tavares, D., Witele, E., Mower, C., Watson, L. K., Collins, J., Eltringham, G., Crudgington, D., Macklin, B., Iturriza-Gomara, M., Lucaci, A. O., McClure, P. C., Carlile, M., Holmes, N., Storey, N., Rooke, S., Yebra, G., Craine, N., Perry, M., Alikhan, N. F., Bridgett, S., Cook, K. F., Fearn, C., Goudarzi, S., Lyons, R. A., Williams, T., Haldenby, S. T., Durham, J., Leonard, S., Davies, R. M., Batra, R., Blane, B., Spyer, M. J., Smith, P., Yavus, M., Williams, R. J., Mahanama, A. I. K., Samaraweera, B., Girgis, S. T., Hansford, S. E., Green, A., Beaver, C., Bellis, K. L., Dorman, M. J., Kay, S., Prestwood, L., Rajatileka, S., Quick, J., Poplawski, R., Reynolds, N., Mack, A., Morriss, A., Whalley, T., Patel, B., Georgana, I., Hosmillo, M., Pinckert, M. L., Stockton, J., Henderson, J. H., Hollis, A., Stanley, W., Yew, W. C., Myers, R., Thornton, A., Adams, A., Annett, T., Asad, H., Birchley, A., Coombes, J., Evans, J. M., Fina, L., Gatica-Wilcox, B., Gilbert, L., Graham, L., Hey, J., Hilvers, E., Jones, S., Jones, H., Kumziene-Summerhayes, S., McKerr, C., Powell, J., Pugh, G., Taylor, S., Trotter, A. J., Williams, C. A., Kermack, L. M., Foulkes, B. H., Gallis, M., Hornsby, H. R., Louka, S. F., Pohare, M., Wolverson, P., Zhang, P., MacIntyre-Cockett, G., Trebes, A., Moll, R. J., Ferguson, L., Goldstein, E. J., Maclean, A., Tomb, R., Starinskij, I., Thomson, L., Southgate, J., Kraemer, M. U. G., Raghwani, J., Zarebski, A. E., Boyd, O., Geidelberg, L., Illingworth, C. J., Jackson, C., Pascall, D., Vattipally, S., Freeman, T. M., Hsu, S. N., Lindsey, B. B., James, K., Lewis, K., Tonkin-Hill, G., Tovar-Corona, J. M., Cox, M., Abudahab, K., Menegazzo, M., Taylor, B. E. W., Yeats, C. A., Mukaddas, A., Wright, D. W., de Oliveira Martins, L., Colquhoun, R., Hill, V., Jackson, B., McCrone, J. T., Medd, N., Scher, E., Keatley, J. P., Curran, T., Morgan, S., Maxwell, P., Smith, K., Eldirdiri, S., Kenyon, A., Holmes, A. H., Price, J. R., Wyatt, T., Mather, A. E., Skvortsov, T., Hartley, J. A., Guest, M., Kitchen, C., Merrick, I., Munn, R., Bertolusso, B., Lynch, J., Vernet, G., Kirk, S., Wastnedge, E., Stanley, R., Idle, G., Bradley, D. T., Poyner, J., Mori, M., Jones, O., Wright, V., Brooks, E., Churcher, C. M., Fragakis, M., Galai, K., Jermy, A., Judges, S., McManus, G. M., Smith, K. S., Westwick, E., Attwood, S. W., Bolt, F., Davies, A., De Lacy, E., Downing, F., Edwards, S., Meadows, L., Jeremiah, S., Smith, N., Foulser, L., Charalampous, T., Patel, A., Berry, L., Boswell, T., Fleming, V. M., Howson-Wells, H. C., Joseph, A., Khakh, M., Lister, M. M., Bird, P. W., Fallon, K., Helmer, T., McMurray, C. L., Odedra, M., Shaw, J., Tang, J. W., Willford, N. J., Blakey, V., Raviprakash, V., Sheriff, N., Williams, L. A., Feltwell, T., Bedford, L., Cargill, J. S., Hughes, W., Moore, J., Stonehouse, S., Atkinson, L., Lee, J. C. D., Shah, D., Alcolea-Medina, A., Ohemeng-Kumi, N., Ramble, J., Sehmi, J., Williams, R., Chatterton, W., Pusok, M., Everson, W., Castigador, A., Macnaughton, E., El Bouzidi, K., Lampejo, T., Sudhanva, M., Breen, C., Sluga, G., Ahmad, S. S. Y., George, R. P., Machin, N. W., Binns, D., James, V., Blacow, R., Coupland, L., Smith, L., Barton, E., Padgett, D., Scott, G., Cross, A., Mirfenderesky, M., Greenaway, J., Cole, K., Clarke, P., Duckworth, N., Walsh, S., Bicknell, K., Impey, R., Wyllie, S., Hopes, R., Bishop, C., Chalker, V., Harrison, I., Gifford, L., Molnar, Z., Auckland, C., Evans, C., Johnson, K., Partridge, D. G., Raza, M., Baker, P., Bonner, S., Essex, S., Murray, L. J., Lawton, A. I., Burton-Fanning, S., Payne, B. A. I., Waugh, S., Gomes, A. N., Kimuli, M., Murray, D. R., Ashfield, P., Dobie, D., Ashford, F., Best, A., Crawford, L., Cumley, N., Mayhew, M., Megram, O., Mirza, J., Moles-Garcia, E., Percival, B., Driscoll, M., Ensell, L., Lowe, H. L., Maftei, L., Mondani, M., Chaloner, N. J., Cogger, B. J., Easton, L. J., Huckson, H., Lewis, J., Lowdon, S., Malone, C. S., Munemo, F., Mutingwende, M., Nicodemi, R., Podplomyk, O., Somassa, T., Beggs, A., Richter, A., Cormie, C., Dias, J., Forrest, S., Higginson, E. E., Maes, M., Young, J., Davidson, R. K., Jackson, K. A., Turtle, L., Keeley, A. J., Ball, J., Byaruhanga, T., Chappell, J. G., Dey, J., Hill, J. D., Park, E. J., Fanaie, A., Hilson, R. A., Yaze, G., Lo, S., Afifi, S., Beer, R., Maksimovic, J., McCluggage, K., Spellman, K., Bresner, C., Fuller, W., Marchbank, A., Workman, T., Shelest, E., Debebe, J., Sang, F., Zamudio, M. E., Francois, S., Gutierrez, B., Vasylyeva, T. I., Flaviani, F., Ragonnet-Cronin, M, Smollett, K. L., Broos, A., Mair, D., Nichols, J., Nomikou, K., Tong, L., Tsatsani, I., O’Brien, S., Rushton, S., Sanderson, R., Perkins, J., Cotton, S., Gallagher, A., Allara, E., Pearson, C., Bibby, D., Dabrera, G., Ellaby, N., Gallagher, E., Hubb, J., Lackenby, A., Lee, D., Manesis, N., Mbisa, T., Platt, S., Twohig, K. A., Morgan, M., Aydin, A., Baker, D. J., Foster-Nyarko, E., Prosolek, S. J., Rudder, S., Baxter, C., Carvalho, S. F., Lavin, D., Mariappan, A., Radulescu, C., Singh, A., Tang, M., Morcrette, H., Bayzid, N., Cotic, M., Balcazar, C. E, Gallagher, M. D., Maloney, D., Stanton, T. D., Williamson, K. A., Manley, R., Michelsen, M. L., Sambles, C. M., Studholme, D. J., Warwick-Dugdale, J., Eccles, R., Gemmell, M., Gregory, R., Hughes, M., Nelson, C., Rainbow, L., Vamos, E. E., Webster, H. J., Whitehead, M., Wierzbicki, C., Angyal, A., Green, L. R., Whiteley, M., Betteridge, E., Bronner, I. F., Farr, B. W., Goodwin, S., Lensing, S. V., McCarthy, S. A., Quail, M. A., Rajan, D., Redshaw, N. M., Scott, C., Shirley, L., Thurston, S. A. J., Rowe, W., Gaskin, A., Le-Viet, T., Bonfield, J., Liddle, J., Whitwham, A., Wilkinson, S. A. J., Sparks, N., Kele, B., Peacock, T. P., Robson, S. C., Connor, T. R., Loman, N. J., Golubchik, T., Martinez Nunez, R. T., Bonsall, D., Rambaut, A., Snell, L. B., Livett, R., Ludden, C., Corden, S., Nastouli, E., Nebbia, G., Johnston, I., Lythgoe, K., Estee Torok, M., Goodfellow, I. G., Prieto, J. A., Saeed, K., Jackson, D. K., Houlihan, C., Frampton, D., Hamilton, W. L., Witney, A. A., Bucca, G., Pope, C. F., Moore, C., Thomson, E. C., Harrison, E. M., Smith, C. P., Rogan, F., Beckwith, S. M., Murray, A., Singleton, D., Eastick, K., Sheridan, L. A., Randell, P., Jackson, L. M., Ariani, C. V., Gonçalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Moses, S., Nicholls, S., Bull, M., Amato, R., Smith, D. L., Aanensen, D. M., Barrett, J. C., Aggarwal, D., Shepherd, J. G., Curran, M. D., Parmar, S., Parker, M. D., Williams, C., Glaysher, S., Underwood, A. P., Bashton, M., Pacchiarini, N., Loveson, K. F., Byott, M., Carabelli, A. M., Templeton, K. E., de Silva, T. I., Wang, D., Langford, C. F., Sillitoe, J., Gunson, R. N., Cottrell, S., O’Grady, J., Kwiatkowski, D., Lillie, P. J., Cortes, N., Moore, N., Thomas, C., Burns, P. J., Mahungu, T. W., Liggett, S., Beckett, A. H., Holden, M. T. G., Levett, L. J., Osman, H., Hassan-Ibrahim, M. O., Simpson, D. A., Chand, M., Gupta, R. K., Darby, A. C., Paterson, S., Pybus, O. G., Volz, E. M., de Angelis, D., Robertson, D. L., Page, A. J., Martincorena, I., Aigrain, L., Bassett, A. R., Wong, N., Taha, Y., Erkiert, M. J., Spencer Chapman, M. H., Dewar, R., McHugh, M. P., Mookerjee, S., Aplin, S., Harvey, M., Sass, T., Umpleby, H., Wheeler, H., McKenna, J. P., Warne, B., Taylor, J. F., Chaudhry, Y., Izuagbe, R., Jahun, A. S., Young, G. R., McMurray, C., McCann, C. M., Nelson, A., Elliott, S., Price, A., Crown, M. R., Rey, S, Roy, S., Temperton, B., Shaaban, S., Hesketh, A. R., Laing, K. G., Monahan, I. M., Heaney, J., Pelosi, E., Silviera, S., Wilson-Davies, E., Fryer, H., Adams, H., du Plessis, L., Johnson, R., Harvey, W. T., Hughes, J., Orton, R. J., Spurgin, L. G., Bourgeois, Y., Ruis, C., O’Toole, Á., Gourtovaia, M., Sanderson, T., Fraser, C., Edgeworth, J., Breuer, J., Michell, S. L., Todd, J. A., John, M., Buck, D., Gajee, K., Kay, G. L., Peacock, S. J., Heyburn, D., Kitchman, K., McNally, A., Pritchard, D. T., Dervisevic, S., Muir, P., Robinson, E., Vipond, B. B., Ramadan, N. A., Jeanes, C., Weldon, D., Catalan, J., Jones, N., da Silva Filipe, A., Fuchs, M., Miskelly, J., Jeffries, A. R., Oliver, K., Park, N. R., Ash, A., Koshy, C., Barrow, M., Buchan, S. L., Mantzouratou, A., Clark, G., Holmes, C. W., Campbell, S., Davis, T., Tan, N. K., Brown, J. R., Harris, K. A., Kidd, S. P., Grant, P. R., Xu-McCrae, L., Cox, A., Madona, P., Pond, M., Randell, P. A., Withell, K. T., Graham, C., Denton-Smith, R., Swindells, E., Turnbull, R., Sloan, T. J., Bosworth, A., Hutchings, S., Pymont, H. M., Casey, A., Ratcliffe, L., Jones, C. R., Knight, B. A., Haque, T., Hart, J., Irish-Tavares, D., Witele, E., Mower, C., Watson, L. K., Collins, J., Eltringham, G., Crudgington, D., Macklin, B., Iturriza-Gomara, M., Lucaci, A. O., McClure, P. C., Carlile, M., Holmes, N., Storey, N., Rooke, S., Yebra, G., Craine, N., Perry, M., Alikhan, N. F., Bridgett, S., Cook, K. F., Fearn, C., Goudarzi, S., Lyons, R. A., Williams, T., Haldenby, S. T., Durham, J., Leonard, S., Davies, R. M., Batra, R., Blane, B., Spyer, M. J., Smith, P., Yavus, M., Williams, R. J., Mahanama, A. I. K., Samaraweera, B., Girgis, S. T., Hansford, S. E., Green, A., Beaver, C., Bellis, K. L., Dorman, M. J., Kay, S., Prestwood, L., Rajatileka, S., Quick, J., Poplawski, R., Reynolds, N., Mack, A., Morriss, A., Whalley, T., Patel, B., Georgana, I., Hosmillo, M., Pinckert, M. L., Stockton, J., Henderson, J. H., Hollis, A., Stanley, W., Yew, W. C., Myers, R., Thornton, A., Adams, A., Annett, T., Asad, H., Birchley, A., Coombes, J., Evans, J. M., Fina, L., Gatica-Wilcox, B., Gilbert, L., Graham, L., Hey, J., Hilvers, E., Jones, S., Jones, H., Kumziene-Summerhayes, S., McKerr, C., Powell, J., Pugh, G., Taylor, S., Trotter, A. J., Williams, C. A., Kermack, L. M., Foulkes, B. H., Gallis, M., Hornsby, H. R., Louka, S. F., Pohare, M., Wolverson, P., Zhang, P., MacIntyre-Cockett, G., Trebes, A., Moll, R. J., Ferguson, L., Goldstein, E. J., Maclean, A., Tomb, R., Starinskij, I., Thomson, L., Southgate, J., Kraemer, M. U. G., Raghwani, J., Zarebski, A. E., Boyd, O., Geidelberg, L., Illingworth, C. J., Jackson, C., Pascall, D., Vattipally, S., Freeman, T. M., Hsu, S. N., Lindsey, B. B., James, K., Lewis, K., Tonkin-Hill, G., Tovar-Corona, J. M., Cox, M., Abudahab, K., Menegazzo, M., Taylor, B. E. W., Yeats, C. A., Mukaddas, A., Wright, D. W., de Oliveira Martins, L., Colquhoun, R., Hill, V., Jackson, B., McCrone, J. T., Medd, N., Scher, E., Keatley, J. P., Curran, T., Morgan, S., Maxwell, P., Smith, K., Eldirdiri, S., Kenyon, A., Holmes, A. H., Price, J. R., Wyatt, T., Mather, A. E., Skvortsov, T., Hartley, J. A., Guest, M., Kitchen, C., Merrick, I., Munn, R., Bertolusso, B., Lynch, J., Vernet, G., Kirk, S., Wastnedge, E., Stanley, R., Idle, G., Bradley, D. T., Poyner, J., Mori, M., Jones, O., Wright, V., Brooks, E., Churcher, C. M., Fragakis, M., Galai, K., Jermy, A., Judges, S., McManus, G. M., Smith, K. S., Westwick, E., Attwood, S. W., Bolt, F., Davies, A., De Lacy, E., Downing, F., Edwards, S., Meadows, L., Jeremiah, S., Smith, N., Foulser, L., Charalampous, T., Patel, A., Berry, L., Boswell, T., Fleming, V. M., Howson-Wells, H. C., Joseph, A., Khakh, M., Lister, M. M., Bird, P. W., Fallon, K., Helmer, T., McMurray, C. L., Odedra, M., Shaw, J., Tang, J. W., Willford, N. J., Blakey, V., Raviprakash, V., Sheriff, N., Williams, L. A., Feltwell, T., Bedford, L., Cargill, J. S., Hughes, W., Moore, J., Stonehouse, S., Atkinson, L., Lee, J. C. D., Shah, D., Alcolea-Medina, A., Ohemeng-Kumi, N., Ramble, J., Sehmi, J., Williams, R., Chatterton, W., Pusok, M., Everson, W., Castigador, A., Macnaughton, E., El Bouzidi, K., Lampejo, T., Sudhanva, M., Breen, C., Sluga, G., Ahmad, S. S. Y., George, R. P., Machin, N. W., Binns, D., James, V., Blacow, R., Coupland, L., Smith, L., Barton, E., Padgett, D., Scott, G., Cross, A., Mirfenderesky, M., Greenaway, J., Cole, K., Clarke, P., Duckworth, N., Walsh, S., Bicknell, K., Impey, R., Wyllie, S., Hopes, R., Bishop, C., Chalker, V., Harrison, I., Gifford, L., Molnar, Z., Auckland, C., Evans, C., Johnson, K., Partridge, D. G., Raza, M., Baker, P., Bonner, S., Essex, S., Murray, L. J., Lawton, A. I., Burton-Fanning, S., Payne, B. A. I., Waugh, S., Gomes, A. N., Kimuli, M., Murray, D. R., Ashfield, P., Dobie, D., Ashford, F., Best, A., Crawford, L., Cumley, N., Mayhew, M., Megram, O., Mirza, J., Moles-Garcia, E., Percival, B., Driscoll, M., Ensell, L., Lowe, H. L., Maftei, L., Mondani, M., Chaloner, N. J., Cogger, B. J., Easton, L. J., Huckson, H., Lewis, J., Lowdon, S., Malone, C. S., Munemo, F., Mutingwende, M., Nicodemi, R., Podplomyk, O., Somassa, T., Beggs, A., Richter, A., Cormie, C., Dias, J., Forrest, S., Higginson, E. E., Maes, M., Young, J., Davidson, R. K., Jackson, K. A., Turtle, L., Keeley, A. J., Ball, J., Byaruhanga, T., Chappell, J. G., Dey, J., Hill, J. D., Park, E. J., Fanaie, A., Hilson, R. A., Yaze, G., Lo, S., Afifi, S., Beer, R., Maksimovic, J., McCluggage, K., Spellman, K., Bresner, C., Fuller, W., Marchbank, A., Workman, T., Shelest, E., Debebe, J., Sang, F., Zamudio, M. E., Francois, S., Gutierrez, B., Vasylyeva, T. I., Flaviani, F., Ragonnet-Cronin, M, Smollett, K. L., Broos, A., Mair, D., Nichols, J., Nomikou, K., Tong, L., Tsatsani, I., O’Brien, S., Rushton, S., Sanderson, R., Perkins, J., Cotton, S., Gallagher, A., Allara, E., Pearson, C., Bibby, D., Dabrera, G., Ellaby, N., Gallagher, E., Hubb, J., Lackenby, A., Lee, D., Manesis, N., Mbisa, T., Platt, S., Twohig, K. A., Morgan, M., Aydin, A., Baker, D. J., Foster-Nyarko, E., Prosolek, S. J., Rudder, S., Baxter, C., Carvalho, S. F., Lavin, D., Mariappan, A., Radulescu, C., Singh, A., Tang, M., Morcrette, H., Bayzid, N., Cotic, M., Balcazar, C. E, Gallagher, M. D., Maloney, D., Stanton, T. D., Williamson, K. A., Manley, R., Michelsen, M. L., Sambles, C. M., Studholme, D. J., Warwick-Dugdale, J., Eccles, R., Gemmell, M., Gregory, R., Hughes, M., Nelson, C., Rainbow, L., Vamos, E. E., Webster, H. J., Whitehead, M., Wierzbicki, C., Angyal, A., Green, L. R., Whiteley, M., Betteridge, E., Bronner, I. F., Farr, B. W., Goodwin, S., Lensing, S. V., McCarthy, S. A., Quail, M. A., Rajan, D., Redshaw, N. M., Scott, C., Shirley, L., Thurston, S. A. J., Rowe, W., Gaskin, A., Le-Viet, T., Bonfield, J., Liddle, J., and Whitwham, A.
Abstract: Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation.There is an apparent selective pressure for mutations that aid cell–cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted. © The Author(s) 2022. Published by Oxford University Press.

21. SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2

Author: Eales, O, Page, AJ, de Oliveira Martins, L, Wang, H, Bodinier, B, Haw, D, Jonnerby, J, Atchison, C, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Nunez, RTM, Bonsall, D, Rambaut, A, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Chapman, MHS, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O’Toole, Á, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N - F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Cox, MG, Abudahab, K, Menegazzo, M, MEng, BEWT, Yeats, CA, Mukaddas, A, Wright, DW, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J - P, Curran, T, Morgan, S, Maxwell, P, Smith, K, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Stanley, R, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L - A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea-Medina, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, Bouzidi, KE, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O’Brien, PS, Rushton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, Whitwham, A, Ashby, D, Barclay, W, Taylor, G, Cooke, G, Ward, H, Darzi, A, Riley, S, Chadeau-Hyam, M, Donnelly, CA, Elliott, P, The COVID-19 Genomics UK (COG-UK) Consortium, Eales, O, Page, AJ, de Oliveira Martins, L, Wang, H, Bodinier, B, Haw, D, Jonnerby, J, Atchison, C, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Nunez, RTM, Bonsall, D, Rambaut, A, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Chapman, MHS, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O’Toole, Á, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N - F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Cox, MG, Abudahab, K, Menegazzo, M, MEng, BEWT, Yeats, CA, Mukaddas, A, Wright, DW, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J - P, Curran, T, Morgan, S, Maxwell, P, Smith, K, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Stanley, R, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L - A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea-Medina, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, Bouzidi, KE, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O’Brien, PS, Rushton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, Whitwham, A, Ashby, D, Barclay, W, Taylor, G, Cooke, G, Ward, H, Darzi, A, Riley, S, Chadeau-Hyam, M, Donnelly, CA, Elliott, P, and The COVID-19 Genomics UK (COG-UK) Consortium
Abstract: Background: Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods: We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results: We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions: As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals. © 2022, The Author(s).

22. COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: a prospective observational cohort study

Author: Kläser, K., Molteni, E., Graham, M., Canas, L. S., Österdahl, M. F., Antonelli, M., Chen, L., Deng, J., Murray, B., Kerfoot, E., Wolf, J., May, A., Fox, B., Capdevila, J., Aanensen, D. M., Abudahab, K., Adams, H., Adams, A., Afifi, S., Aggarwal, D., Ahmad, S. S. Y., Aigrain, L., Alcolea-Medina, A., Alikhan, N-F, Allara, E., Amato, R., Angyal, A., Annett, T., Aplin, S., Ariani, C. V., Asad, H., Ash, A., Ashfield, P., Ashford, F., Atkinson, L., Attwood, S. W., Auckland, C., Aydin, A., Baker, D. J., Baker, P., Balcazar, C. E., Ball, J., Barrett, J. C., Barrow, M., Barton, E., Bashton, M., Bassett, A. R., Batra, R., Baxter, C., Bayzid, N., Beaver, C., Beckett, A. H., Beckwith, S. M., Bedford, L., Beer, R., Beggs, A., Bellis, K. L., Berry, L., Bertolusso, B., Best, A., Betteridge, E., Bibby, D., Bicknell, K., Binns, D., Birchley, A., Bird, P. W., Bishop, C., Blacow, R., Blakey, V., Blane, B., Bolt, F., Bonfield, J., Bonner, S., Bonsall, D., Boswell, T., Bosworth, A., Bourgeois, Y., Boyd, O., Bradley, D. T., Breen, C., Bresner, C., Breuer, J., Bridgett, S., Bronner, I. F., Brooks, E., Broos, A., Brown, J. R., Bucca, G., Buchan, S. L., Buck, D., Bull, M., Burns, P. J., Burton-Fanning, S., Byaruhanga, T., Byott, M., Campbell, S., Carabelli, A. M., Cargill, J. S., Carlile, M., Carvalho, S. F., Casey, A., Castigador, A., Catalan, J., Chalker, V., Chaloner, N. J., Chand, M., Chappell, J. G., Charalampous, T., Chatterton, W., Chaudhry, Y., Churcher, C. M., Clark, G., Clarke, P., Cogger, B. J., Cole, K., Collins, J., Colquhoun, R., Connor, T. R., Cook, K. F., Coombes, J., Corden, S., Cormie, C., Cortes, N., Cotic, M., Cotton, S., Cottrell, S., Coupland, L., Cox, M. G., Cox, A., Craine, N., Crawford, L., Cross, A., Crown, M. R., Crudgington, D., Cumley, N., Curran, T., Curran, M. D., da Silva Filipe, A., Dabrera, G., Darby, A. C., Davidson, R. K., Davies, A., Davies, R. M., Davis, T., de Angelis, D., De Lacy, E., de Oliveira Martins, L., de Silva, T. I., Debebe, J., Denton-Smith, R., Dervisevic, S., Dewar, R., Dey, J., Dias, J., Dobie, D., Dorman, M. J., Downing, F., Driscoll, M., du Plessis, L., Duckworth, N., Durham, J., Eastick, K., Easton, L. J., Eccles, R., Edgeworth, J., Edwards, S., Bouzidi, K. E., Eldirdiri, S., Ellaby, N., Elliott, S., Eltringham, G., Ensell, L., Erkiert, M. J., Zamudio, M. E., Essex, S., Evans, J. M., Evans, C., Everson, W., Fairley, D. J., Fallon, K., Fanaie, A., Farr, B. W., Fearn, C., Feltwell, T., Ferguson, L., Fina, L., Flaviani, F., Fleming, V. M., Forrest, S., Foster-Nyarko, E., Foulkes, B. H., Foulser, L., Fragakis, M., Frampton, D., Francois, S., Fraser, C., Freeman, T. M., Fryer, H., Fuchs, M., Fuller, W., Gajee, K., Galai, K., Gallagher, A., Gallagher, E., Gallagher, M. D., Gallis, M., Gaskin, A., Gatica-Wilcox, B., Geidelberg, L., Gemmell, M., Georgana, I., George, R. P., Gifford, L., Gilbert, L., Girgis, S. T., Glaysher, S., Goldstein, E. J., Golubchik, T., Gomes, A. N., Gonçalves, S., Goodfellow, I. G., Goodwin, S., Goudarzi, S., Gourtovaia, M., Graham, C. A., Graham, L., Grant, P. R., Green, L. R., Green, A., Greenaway, J., Gregory, R., Guest, M., Gunson, R. N., Gupta, R. K., Gutierrez, B., Haldenby, S. T., Hamilton, W. L., Hansford, S. E., Haque, T., Harris, K. A., Harrison, I., Harrison, E. M., Hart, J., Hartley, .J. A., Harvey, W. T., Harvey, M., Hassan-Ibrahim, M. O., Heaney, J., Helmer, T., Henderson, J. H., Hesketh, A. R., Hey, J., Heyburn, D., Higginson, E. E., Hill, V., Hill, J. D., Hilson, R. A., Hilvers, E., Holden, M. T. G., Hollis, A., Holmes, C. W., Holmes, N., Holmes, A. H., Hopes, R., Hornsby, H. R., Hosmillo, M., Houlihan, C., Howson-Wells, H. C., Hsu, S. N., Hubb, J., Huckson, H., Hughes, W., Hughes, J., Hughes, M., Hutchings, S., Idle, G, Illingworth, CJ, Impey, R, Irish-Tavares, D, Iturriza-Gomara, M, Izuagbe, R, Jackson, C, Jackson, B, Jackson, LM, Jackson, KA, Jackson, DK, Jahun, AS, James, V, James, K, Jeanes, C, Jeffries, AR, Jeremiah, S, Jermy, A, John, M, Johnson, R, Johnson, K, Johnston, I, Jones, O, Jones, S, Jones, H, Jones, CR, Jones, N, Joseph, A, Judges, S, Kay, GL, Kay, S, Keatley, J - P, Keeley, AJ, Kenyon, A, Kermack, LM, Khakh, M, Kidd, SP, Kimuli, M, Kirk, S, Kitchen, C, Kitchman, K, Knight, BA, Koshy, C, Kraemer, MUG, Kumziene-Summerhayes, S, Kwiatkowski, D, Lackenby, A, Laing, KG, Lampejo, T, Langford, CF, Lavin, D, Lawton, AI, Lee, JCD, Lee, D, Lensing, SV, Leonard, S, Levett, LJ, Le-Viet, T, Lewis, J, Lewis, K, Liddle, J, Liggett, S, Lillie, PJ, Lindsey, BB, Lister, MM, Livett, R, Lo, S, Loman, NJ, Loose, MW, Louka, SF, Loveson, KF, Lowdon, S, Lowe, H, Lowe, HL, Lucaci, AO, Ludden, C, Lynch, J, Lyons, RA, Lythgoe, K, Machin, NW, MacIntyre-Cockett, G, Mack, A, Macklin, B, Maclean, A, Macnaughton, E, Madona, P, Maes, M, Maftei, L, Mahanama, AIK, Mahungu, TW, Mair, D, Maksimovic, J, Malone, CS, Maloney, D, Manesis, N, Manley, R, Mantzouratou, A, Marchbank, A, Mariappan, A, Martincorena, I, Nunez, RTM, Mather, AE, Maxwell, P, Mayhew, M, Mbisa, T, McCann, CM, McCarthy, SA, McCluggage, K, McClure, PC, McCrone, JT, McHugh, MP, McKenna, JP, McKerr, C, McManus, GM, McMurray, CL, McMurray, C, McNally, A, Meadows, L, Medd, N, Megram, O, Menegazzo, M, Merrick, I, Michell, SL, Michelsen, ML, Mirfenderesky, M, Mirza, J, Miskelly, J, Moles-Garcia, E, Moll, RJ, Molnar, Z, Monahan, IM, Mondani, M, Mookerjee, S, Moore, C, Moore, J, Moore, N, Morcrette, H, Morgan, S, Morgan, M, Mori, M, Morriss, A, Moses, S, Mower, C, Muir, P, Mukaddas, A, Munemo, F, Munn, R, Murray, A, Murray, LJ, Murray, DR, Mutingwende, M, Myers, R, Nastouli, E, Nebbia, G, Nelson, A, Nelson, C, Nicholls, S, Nichols, J, Nicodemi, R, Nomikou, K, O’Grady, J, O’Brien, S, Odedra, M, Ohemeng-Kumi, N, Oliver, K, Orton, RJ, Osman, H, O’Toole, Á, Pacchiarini, N, Padgett, D, Page, AJ, Park, EJ, Park, NR, Parker, MD, Parmar, S, Partridge, DG, Pascall, D, Patel, A, Patel, B, Paterson, S, Payne, BAI, Peacock, SJ, Pearson, C, Pelosi, E, Percival, B, Perkins, J, Perry, M, Pinckert, ML, Platt, S, Podplomyk, O, Pohare, M, Pond, M, Pope, CF, Poplawski, R, Powell, J, Poyner, J, Prestwood, L, Price, A, Price, JR, Prieto, JA, Pritchard, DT, Prosolek, SJ, Pugh, G, Pusok, M, Pybus, OG, Pymont, HM, Quail, MA, Quick, J, Radulescu, C, Raghwani, J, Ragonnet-Cronin, M, Rainbow, L, Rajan, D, Rajatileka, S, Ramadan, NA, Rambaut, A, Ramble, J, Randell, PA, Randell, P, Ratcliffe, L, Raviprakash, V, Raza, M, Redshaw, NM, Rey, S, Reynolds, N, Richter, A, Robertson, DL, Robinson, E, Robson, SC, Rogan, F, Rooke, S, Rowe, W, Roy, S, Rudder, S, Ruis, C, Rushton, S, Ryan, F, Saeed, K, Samaraweera, B, Sambles, CM, Sanderson, R, Sanderson, T, Sang, F, Sass, T, Scher, E, Scott, G, Scott, C, Sehmi, J, Shaaban, S, Shah, D, Shaw, J, Shelest, E, Shepherd, JG, Sheridan, LA, Sheriff, N, Shirley, L, Sillitoe, J, Silviera, S, Simpson, DA, Singh, A, Singleton, D, Skvortsov, T, Sloan, TJ, Sluga, G, Smith, K, Smith, KS, Smith, P, Smith, DL, Smith, L, Smith, CP, Smith, N, Smollett, KL, Snell, LB, Somassa, T, Southgate, J, Spellman, K, Chapman, MHS, Spurgin, LG, Spyer, MJ, Stanley, R, Stanley, W, Stanton, TD, Starinskij, I, Stockton, J, Stonehouse, S, Storey, N, Studholme, DJ, Sudhanva, M, Swindells, E, Taha, Y, Tan, NK, Tang, JW, Tang, M, Taylor, BEW, Taylor, JF, Taylor, S, Temperton, B, Templeton, KE, Thomas, C, Thomson, L, Thomson, EC, Thornton, A, Thurston, SAJ, Todd, JA, Tomb, R, Tong, L, Tonkin-Hill, G, Torok, ME, Tovar-Corona, JM, Trebes, A, Trotter, AJ, Tsatsani, I, Turnbull, R, Turtle, L, Twohig, KA, Umpleby, H, Underwood, AP, Vamos, EE, Vasylyeva, TI, Vattipally, S, Vernet, G, Vipond, BB, Volz, EM, Walsh, S, Wang, D, Warne, B, Warwick-Dugdale, J, Wastnedge, E, Watkins, J, Watson, LK, Waugh, S, Webster, HJ, Weldon, D, Westwick, E, Whalley, T, Wheeler, H, Whitehead, M, Whiteley, M, Whitwham, A, Wierzbicki, C, Willford, NJ, Williams, L-A, Williams, R, Williams, C, Williams, CA, Williams, RJ, Williams, T, Williamson, KA, Wilson-Davies, E, Witele, E, Withell, KT, Witney, AA, Wolverson, P, Wong, N, Workman, T, Wright, V, Wright, DW, Wyatt, T, Wyllie, S, Xu-McCrae, L., Yavus, M., Yaze, G., Yeats, C. A., Yebra, G., Yew, W. C., Young, G. R., Young, J., Zarebski, A. E., Zhang, P., Modat, M., Hammers, A., Spector, T. D., Steves, C. J., Sudre, C. H., Ourselin, S., Duncan, E. L., Kläser, K., Molteni, E., Graham, M., Canas, L. S., Österdahl, M. F., Antonelli, M., Chen, L., Deng, J., Murray, B., Kerfoot, E., Wolf, J., May, A., Fox, B., Capdevila, J., Aanensen, D. M., Abudahab, K., Adams, H., Adams, A., Afifi, S., Aggarwal, D., Ahmad, S. S. Y., Aigrain, L., Alcolea-Medina, A., Alikhan, N-F, Allara, E., Amato, R., Angyal, A., Annett, T., Aplin, S., Ariani, C. V., Asad, H., Ash, A., Ashfield, P., Ashford, F., Atkinson, L., Attwood, S. W., Auckland, C., Aydin, A., Baker, D. J., Baker, P., Balcazar, C. E., Ball, J., Barrett, J. C., Barrow, M., Barton, E., Bashton, M., Bassett, A. R., Batra, R., Baxter, C., Bayzid, N., Beaver, C., Beckett, A. H., Beckwith, S. M., Bedford, L., Beer, R., Beggs, A., Bellis, K. L., Berry, L., Bertolusso, B., Best, A., Betteridge, E., Bibby, D., Bicknell, K., Binns, D., Birchley, A., Bird, P. W., Bishop, C., Blacow, R., Blakey, V., Blane, B., Bolt, F., Bonfield, J., Bonner, S., Bonsall, D., Boswell, T., Bosworth, A., Bourgeois, Y., Boyd, O., Bradley, D. T., Breen, C., Bresner, C., Breuer, J., Bridgett, S., Bronner, I. F., Brooks, E., Broos, A., Brown, J. R., Bucca, G., Buchan, S. L., Buck, D., Bull, M., Burns, P. J., Burton-Fanning, S., Byaruhanga, T., Byott, M., Campbell, S., Carabelli, A. M., Cargill, J. S., Carlile, M., Carvalho, S. F., Casey, A., Castigador, A., Catalan, J., Chalker, V., Chaloner, N. J., Chand, M., Chappell, J. G., Charalampous, T., Chatterton, W., Chaudhry, Y., Churcher, C. M., Clark, G., Clarke, P., Cogger, B. J., Cole, K., Collins, J., Colquhoun, R., Connor, T. R., Cook, K. F., Coombes, J., Corden, S., Cormie, C., Cortes, N., Cotic, M., Cotton, S., Cottrell, S., Coupland, L., Cox, M. G., Cox, A., Craine, N., Crawford, L., Cross, A., Crown, M. R., Crudgington, D., Cumley, N., Curran, T., Curran, M. D., da Silva Filipe, A., Dabrera, G., Darby, A. C., Davidson, R. K., Davies, A., Davies, R. M., Davis, T., de Angelis, D., De Lacy, E., de Oliveira Martins, L., de Silva, T. I., Debebe, J., Denton-Smith, R., Dervisevic, S., Dewar, R., Dey, J., Dias, J., Dobie, D., Dorman, M. J., Downing, F., Driscoll, M., du Plessis, L., Duckworth, N., Durham, J., Eastick, K., Easton, L. J., Eccles, R., Edgeworth, J., Edwards, S., Bouzidi, K. E., Eldirdiri, S., Ellaby, N., Elliott, S., Eltringham, G., Ensell, L., Erkiert, M. J., Zamudio, M. E., Essex, S., Evans, J. M., Evans, C., Everson, W., Fairley, D. J., Fallon, K., Fanaie, A., Farr, B. W., Fearn, C., Feltwell, T., Ferguson, L., Fina, L., Flaviani, F., Fleming, V. M., Forrest, S., Foster-Nyarko, E., Foulkes, B. H., Foulser, L., Fragakis, M., Frampton, D., Francois, S., Fraser, C., Freeman, T. M., Fryer, H., Fuchs, M., Fuller, W., Gajee, K., Galai, K., Gallagher, A., Gallagher, E., Gallagher, M. D., Gallis, M., Gaskin, A., Gatica-Wilcox, B., Geidelberg, L., Gemmell, M., Georgana, I., George, R. P., Gifford, L., Gilbert, L., Girgis, S. T., Glaysher, S., Goldstein, E. J., Golubchik, T., Gomes, A. N., Gonçalves, S., Goodfellow, I. G., Goodwin, S., Goudarzi, S., Gourtovaia, M., Graham, C. A., Graham, L., Grant, P. R., Green, L. R., Green, A., Greenaway, J., Gregory, R., Guest, M., Gunson, R. N., Gupta, R. K., Gutierrez, B., Haldenby, S. T., Hamilton, W. L., Hansford, S. E., Haque, T., Harris, K. A., Harrison, I., Harrison, E. M., Hart, J., Hartley, .J. A., Harvey, W. T., Harvey, M., Hassan-Ibrahim, M. O., Heaney, J., Helmer, T., Henderson, J. H., Hesketh, A. R., Hey, J., Heyburn, D., Higginson, E. E., Hill, V., Hill, J. D., Hilson, R. A., Hilvers, E., Holden, M. T. G., Hollis, A., Holmes, C. W., Holmes, N., Holmes, A. H., Hopes, R., Hornsby, H. R., Hosmillo, M., Houlihan, C., Howson-Wells, H. C., Hsu, S. N., Hubb, J., Huckson, H., Hughes, W., Hughes, J., Hughes, M., Hutchings, S., Idle, G, Illingworth, CJ, Impey, R, Irish-Tavares, D, Iturriza-Gomara, M, Izuagbe, R, Jackson, C, Jackson, B, Jackson, LM, Jackson, KA, Jackson, DK, Jahun, AS, James, V, James, K, Jeanes, C, Jeffries, AR, Jeremiah, S, Jermy, A, John, M, Johnson, R, Johnson, K, Johnston, I, Jones, O, Jones, S, Jones, H, Jones, CR, Jones, N, Joseph, A, Judges, S, Kay, GL, Kay, S, Keatley, J - P, Keeley, AJ, Kenyon, A, Kermack, LM, Khakh, M, Kidd, SP, Kimuli, M, Kirk, S, Kitchen, C, Kitchman, K, Knight, BA, Koshy, C, Kraemer, MUG, Kumziene-Summerhayes, S, Kwiatkowski, D, Lackenby, A, Laing, KG, Lampejo, T, Langford, CF, Lavin, D, Lawton, AI, Lee, JCD, Lee, D, Lensing, SV, Leonard, S, Levett, LJ, Le-Viet, T, Lewis, J, Lewis, K, Liddle, J, Liggett, S, Lillie, PJ, Lindsey, BB, Lister, MM, Livett, R, Lo, S, Loman, NJ, Loose, MW, Louka, SF, Loveson, KF, Lowdon, S, Lowe, H, Lowe, HL, Lucaci, AO, Ludden, C, Lynch, J, Lyons, RA, Lythgoe, K, Machin, NW, MacIntyre-Cockett, G, Mack, A, Macklin, B, Maclean, A, Macnaughton, E, Madona, P, Maes, M, Maftei, L, Mahanama, AIK, Mahungu, TW, Mair, D, Maksimovic, J, Malone, CS, Maloney, D, Manesis, N, Manley, R, Mantzouratou, A, Marchbank, A, Mariappan, A, Martincorena, I, Nunez, RTM, Mather, AE, Maxwell, P, Mayhew, M, Mbisa, T, McCann, CM, McCarthy, SA, McCluggage, K, McClure, PC, McCrone, JT, McHugh, MP, McKenna, JP, McKerr, C, McManus, GM, McMurray, CL, McMurray, C, McNally, A, Meadows, L, Medd, N, Megram, O, Menegazzo, M, Merrick, I, Michell, SL, Michelsen, ML, Mirfenderesky, M, Mirza, J, Miskelly, J, Moles-Garcia, E, Moll, RJ, Molnar, Z, Monahan, IM, Mondani, M, Mookerjee, S, Moore, C, Moore, J, Moore, N, Morcrette, H, Morgan, S, Morgan, M, Mori, M, Morriss, A, Moses, S, Mower, C, Muir, P, Mukaddas, A, Munemo, F, Munn, R, Murray, A, Murray, LJ, Murray, DR, Mutingwende, M, Myers, R, Nastouli, E, Nebbia, G, Nelson, A, Nelson, C, Nicholls, S, Nichols, J, Nicodemi, R, Nomikou, K, O’Grady, J, O’Brien, S, Odedra, M, Ohemeng-Kumi, N, Oliver, K, Orton, RJ, Osman, H, O’Toole, Á, Pacchiarini, N, Padgett, D, Page, AJ, Park, EJ, Park, NR, Parker, MD, Parmar, S, Partridge, DG, Pascall, D, Patel, A, Patel, B, Paterson, S, Payne, BAI, Peacock, SJ, Pearson, C, Pelosi, E, Percival, B, Perkins, J, Perry, M, Pinckert, ML, Platt, S, Podplomyk, O, Pohare, M, Pond, M, Pope, CF, Poplawski, R, Powell, J, Poyner, J, Prestwood, L, Price, A, Price, JR, Prieto, JA, Pritchard, DT, Prosolek, SJ, Pugh, G, Pusok, M, Pybus, OG, Pymont, HM, Quail, MA, Quick, J, Radulescu, C, Raghwani, J, Ragonnet-Cronin, M, Rainbow, L, Rajan, D, Rajatileka, S, Ramadan, NA, Rambaut, A, Ramble, J, Randell, PA, Randell, P, Ratcliffe, L, Raviprakash, V, Raza, M, Redshaw, NM, Rey, S, Reynolds, N, Richter, A, Robertson, DL, Robinson, E, Robson, SC, Rogan, F, Rooke, S, Rowe, W, Roy, S, Rudder, S, Ruis, C, Rushton, S, Ryan, F, Saeed, K, Samaraweera, B, Sambles, CM, Sanderson, R, Sanderson, T, Sang, F, Sass, T, Scher, E, Scott, G, Scott, C, Sehmi, J, Shaaban, S, Shah, D, Shaw, J, Shelest, E, Shepherd, JG, Sheridan, LA, Sheriff, N, Shirley, L, Sillitoe, J, Silviera, S, Simpson, DA, Singh, A, Singleton, D, Skvortsov, T, Sloan, TJ, Sluga, G, Smith, K, Smith, KS, Smith, P, Smith, DL, Smith, L, Smith, CP, Smith, N, Smollett, KL, Snell, LB, Somassa, T, Southgate, J, Spellman, K, Chapman, MHS, Spurgin, LG, Spyer, MJ, Stanley, R, Stanley, W, Stanton, TD, Starinskij, I, Stockton, J, Stonehouse, S, Storey, N, Studholme, DJ, Sudhanva, M, Swindells, E, Taha, Y, Tan, NK, Tang, JW, Tang, M, Taylor, BEW, Taylor, JF, Taylor, S, Temperton, B, Templeton, KE, Thomas, C, Thomson, L, Thomson, EC, Thornton, A, Thurston, SAJ, Todd, JA, Tomb, R, Tong, L, Tonkin-Hill, G, Torok, ME, Tovar-Corona, JM, Trebes, A, Trotter, AJ, Tsatsani, I, Turnbull, R, Turtle, L, Twohig, KA, Umpleby, H, Underwood, AP, Vamos, EE, Vasylyeva, TI, Vattipally, S, Vernet, G, Vipond, BB, Volz, EM, Walsh, S, Wang, D, Warne, B, Warwick-Dugdale, J, Wastnedge, E, Watkins, J, Watson, LK, Waugh, S, Webster, HJ, Weldon, D, Westwick, E, Whalley, T, Wheeler, H, Whitehead, M, Whiteley, M, Whitwham, A, Wierzbicki, C, Willford, NJ, Williams, L-A, Williams, R, Williams, C, Williams, CA, Williams, RJ, Williams, T, Williamson, KA, Wilson-Davies, E, Witele, E, Withell, KT, Witney, AA, Wolverson, P, Wong, N, Workman, T, Wright, V, Wright, DW, Wyatt, T, Wyllie, S, Xu-McCrae, L., Yavus, M., Yaze, G., Yeats, C. A., Yebra, G., Yew, W. C., Young, G. R., Young, J., Zarebski, A. E., Zhang, P., Modat, M., Hammers, A., Spector, T. D., Steves, C. J., Sudre, C. H., Ourselin, S., and Duncan, E. L.
Abstract: The Delta (B.1.617.2) variant was the predominant UK circulating SARS-CoV-2 strain between May and December 2021. How Delta infection compares with previous variants is unknown. This prospective observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly the predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period. 3581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta versus Alpha infection (including fever, sore throat, and headache) and some vice versa (dyspnoea). Symptom burden in the first week was higher with Delta versus Alpha infection; however, the odds of any given symptom lasting ≥ 7 days was either lower or unchanged. Illness duration ≥ 28 days was lower with Delta versus Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1.49) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly reduced the risk of Delta infection (by 69-84%). We conclude that COVID-19 from Delta or Alpha infections is similar. The Delta variant is more transmissible than Alpha; however, current vaccines showed good efficacy against disease. This research framework can be useful for future comparisons with new emerging variants. © 2022, The Author(s).

23. The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis

Author: Pascall, DJ, Vink, E, Blacow, R, Bulteel, N, Campbell, A, Campbell, R, Clifford, S, Davis, C, Filipe, ADS, Sakka, NE, Fjodorova, L, Forrest, R, Goldstein, EJ, Gunson, R, Haughney, J, Holden, MTG, Honour, P, Hughes, J, James, E, Lewis, T, Lycett, S, MacLean, O, McHugh, MP, Mollett, G, Onishi, Y, Parcell, B, Ray, S, Robertson, DL, Shabaan, S, Shepherd, JG, Smollett, KL, Templeton, KE, Wastnedge, E, Wilkie, C, Williams, T, Thomson, EC, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, PA, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Lythgoe, PK, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Cutino-Moguel, T, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, PA, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Kele, B, Aggarwal, D, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Peacock, SJ, de Silva, TI, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O'Grady, J, Kwiatkowski, PD, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, PS, Pybus, OG, Volz, EM, de Angelis, PD, Page, AJ, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, CL, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O'Toole, A, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, PJ, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Heyburn, D, Charalampous, T, Alcolea-Medina, A, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, Anna, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N - F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AI, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Cox, M, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J - P, Curran, T, Morgan, S, Maxwell, PP, Smith, PK, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, PM, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Stanley, R, Idle, G, Bradley, DT, Killough, NF, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Callico, LD, Fragakis, M, Galai, K, Jermy, A, Judges, S, Markov, A, McManus, GM, Smith, KS, Thomas-McEwen, PMD, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L - A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, Bouzidi, KE, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, PS, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Keeley, AJ, Ball, PJ, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O'Brien, S, Rushton, PS, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, Whitwham, A, Pascall, DJ, Vink, E, Blacow, R, Bulteel, N, Campbell, A, Campbell, R, Clifford, S, Davis, C, Filipe, ADS, Sakka, NE, Fjodorova, L, Forrest, R, Goldstein, EJ, Gunson, R, Haughney, J, Holden, MTG, Honour, P, Hughes, J, James, E, Lewis, T, Lycett, S, MacLean, O, McHugh, MP, Mollett, G, Onishi, Y, Parcell, B, Ray, S, Robertson, DL, Shabaan, S, Shepherd, JG, Smollett, KL, Templeton, KE, Wastnedge, E, Wilkie, C, Williams, T, Thomson, EC, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, PA, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Lythgoe, PK, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Cutino-Moguel, T, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, PA, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Kele, B, Aggarwal, D, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Peacock, SJ, de Silva, TI, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O'Grady, J, Kwiatkowski, PD, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, PS, Pybus, OG, Volz, EM, de Angelis, PD, Page, AJ, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, CL, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O'Toole, A, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, PJ, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Heyburn, D, Charalampous, T, Alcolea-Medina, A, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, Anna, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N - F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AI, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Cox, M, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J - P, Curran, T, Morgan, S, Maxwell, PP, Smith, PK, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, PM, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Stanley, R, Idle, G, Bradley, DT, Killough, NF, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Callico, LD, Fragakis, M, Galai, K, Jermy, A, Judges, S, Markov, A, McManus, GM, Smith, KS, Thomas-McEwen, PMD, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L - A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, Bouzidi, KE, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, PS, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Keeley, AJ, Ball, PJ, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O'Brien, S, Rushton, PS, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, and Whitwham, A
Abstract: Objectives The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this. Methods In this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death. Results Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants). Conclusions The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.

24. Tracking SARS-CoV-2 mutations and variants through the COG-UK-Mutation Explorer

Author: Wright, DW, Harvey, WT, Hughes, J, Cox, M, Peacock, TP, Colquhoun, R, Jackson, B, Orton, R, Nielsen, M, Hsu, NS, Harrison, EM, de Silva, TI, Rambaut, A, Peacock, SJ, Robertson, DL, Carabelli, AM, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, PA, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Templeton, KE, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O'Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Page, AJ, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, CL, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O'Toole, Á, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N - F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, de Oliveira Martins, L, Hill, V, McCrone, JT, Medd, N, Scher, E, Keatley, J - P, Curran, T, Morgan, S, Maxwell, P, Smith, K, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Stanley, R, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L - A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea-Medina, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huck-Son, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O'Brien, S, Rush-Ton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, Whitwham, A, Wright, DW, Harvey, WT, Hughes, J, Cox, M, Peacock, TP, Colquhoun, R, Jackson, B, Orton, R, Nielsen, M, Hsu, NS, Harrison, EM, de Silva, TI, Rambaut, A, Peacock, SJ, Robertson, DL, Carabelli, AM, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, PA, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Templeton, KE, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O'Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Page, AJ, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, CL, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O'Toole, Á, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N - F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, de Oliveira Martins, L, Hill, V, McCrone, JT, Medd, N, Scher, E, Keatley, J - P, Curran, T, Morgan, S, Maxwell, P, Smith, K, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Stanley, R, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L - A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea-Medina, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huck-Son, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O'Brien, S, Rush-Ton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, and Whitwham, A
Abstract: COG-UK Mutation Explorer (COG-UK-ME, https://sars2.cvr.gla.ac.uk/cog-uk/—last accessed date 16 March 2022) is a web resource that displays knowledge and analyses on SARS-CoV-2 virus genome mutations and variants circulating in the UK, with a focus on the observed amino acid replacements that have an antigenic role in the context of the human humoral and cellular immune response. This analysis is based on more than 2 million genome sequences (as of March 2022) for UK SARS-CoV-2 data held in the CLIMB-COVID centralised data environment. COG-UK-ME curates these data and displays analyses that are cross-referenced to experimental data collated from the primary literature. The aim is to track mutations of immunological importance that are accumulating in current variants of concern and variants of interest that could alter the neutralising activity of monoclonal antibodies (mAbs), convalescent sera, and vaccines. Changes in epitopes recognised by T cells, including those where reduced T cell binding has been demonstrated, are reported. Mutations that have been shown to confer SARS-CoV-2 resistance to antiviral drugs are also included. Using visualisation tools, COG-UK-ME also allows users to identify the emergence of variants carrying mutations that could decrease the neutralising activity of both mAbs present in therapeutic cocktails, e.g. Ronapreve. COG-UK-ME tracks changes in the frequency of combinations of mutations and brings together the curated literature on the impact of those mutations on various functional aspects of the virus and therapeutics. Given the unpredictable nature of SARS-CoV-2 as exemplified by yet another variant of concern, Omicron, continued surveillance of SARS-CoV-2 remains imperative to monitor virus evolution linked to the efficacy of therapeutics.

25. Spatial growth rate of emerging SARS-CoV-2 lineages in England, September 2020-December 2021

Author: Smallman-Raynor, MR, Cliff, AD, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, A, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, PA, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O'Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Page, AJ, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, CL, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O'Toole, Á, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N - F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Cox, M, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J - P, Curran, T, Morgan, S, Maxwell, P, Smith, K, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Stanley, R, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L - A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea-Medina, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O'Brien, S, Rushton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, Whitwham, A, Smallman-Raynor, MR, Cliff, AD, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, A, Snell, LB, Livett, R, Ludden, C, Corden, S, Nastouli, E, Nebbia, G, Johnston, I, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Jackson, DK, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, PA, Jackson, LM, Ariani, CV, Gonçalves, S, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Amato, R, Smith, DL, Aanensen, DM, Barrett, JC, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Sillitoe, J, Gunson, RN, Cottrell, S, O'Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Page, AJ, Martincorena, I, Aigrain, L, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, CL, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O'Toole, Á, Gourtovaia, M, Sanderson, T, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Weldon, D, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Oliver, K, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N - F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Durham, J, Leonard, S, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Beaver, C, Bellis, KL, Dorman, MJ, Kay, S, Prestwood, L, Rajatileka, S, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Taylor, S, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, James, K, Lewis, K, Tonkin-Hill, G, Tovar-Corona, JM, Cox, M, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J - P, Curran, T, Morgan, S, Maxwell, P, Smith, K, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Stanley, R, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Foulser, L, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L - A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea-Medina, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Harrison, I, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Driscoll, M, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Lo, S, Afifi, S, Beer, R, Maksimovic, J, McCluggage, K, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O'Brien, S, Rushton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Betteridge, E, Bronner, IF, Farr, BW, Goodwin, S, Lensing, SV, McCarthy, SA, Quail, MA, Rajan, D, Redshaw, NM, Scott, C, Shirley, L, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Bonfield, J, Liddle, J, and Whitwham, A
Abstract: This paper uses a robust method of spatial epidemiological analysis to assess the spatial growth rate of multiple lineages of SARS-CoV-2 in the local authority areas of England, September 2020–December 2021. Using the genomic surveillance records of the COVID-19 Genomics UK (COG-UK) Consortium, the analysis identifies a substantial (7.6-fold) difference in the average rate of spatial growth of 37 sample lineages, from the slowest (Delta AY.4.3) to the fastest (Omicron BA.1). Spatial growth of the Omicron (B.1.1.529 and BA) variant was found to be 2.81× faster than the Delta (B.1.617.2 and AY) variant and 3.76× faster than the Alpha (B.1.1.7 and Q) variant. In addition to AY.4.2 (a designated variant under investigation, VUI-21OCT-01), three Delta sublineages (AY.43, AY.98 and AY.120) were found to display a statistically faster rate of spatial growth than the parent lineage and would seem to merit further investigation. We suggest that the monitoring of spatial growth rates is a potentially valuable adjunct to outbreak response procedures for emerging SARS-CoV-2 variants in a defined population.

26. Protocol for the EACH trial: a multicentre phase II study evaluating the safety and antitumour activity of the combination of avelumab, an anti-PD-L1 agent, and cetuximab, as any line treatment for patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC) in the UK.

Author: Ng K, Metcalf R, Sacco J, Kong A, Wheeler G, Forsyth S, Bhat R, Ward J, Ensell L, Lowe H, Spanswick V, Hartley J, White L, Lloyd-Dehler E, and Forster M
Subjects: Humans, Cetuximab therapeutic use, Squamous Cell Carcinoma of Head and Neck drug therapy, B7-H1 Antigen, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Antibodies, Monoclonal, United Kingdom, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Clinical Trials, Phase II as Topic, Carcinoma, Squamous Cell drug therapy, Head and Neck Neoplasms drug therapy, Antineoplastic Agents therapeutic use
Abstract: Introduction: Head and neck cancer is the eighth most common cancer in the UK. Current standard of care treatment for patients with recurrent/metastatic squamous cell head and neck carcinoma (HNSCC) is platinum-based chemotherapy combined with the anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, cetuximab. However, most patients will have poor median overall survival (OS) of 6-9 months despite treatment. HNSCC tumours exhibit an immune landscape poised to respond to immunotherapeutic approaches, with most tumours expressing the immunosuppressive receptor programmed death-ligand 1 (PD-L1). We undertook the current study to determine the safety and efficacy of avelumab, a monoclonal antibody targeting the interaction between PD-L1 and its receptor on cytotoxic T-cells, in combination with cetuximab., Methods and Analysis: This is a multi-centre, single-arm dose de-escalation phase II safety and efficacy study of avelumab combined with cetuximab; the study was to progress to a randomised phase II trial, however, the study will now complete after the safety run-in component. Up to 16 participants with histologically/cytologically recurrent/metastatic squamous cell carcinoma (including HNSCC) who have not received cetuximab previously will be recruited. All patients will receive 10 mg/kg avelumab and cetuximab (500, 400 or 300 mg/m 2 depending on the cohort open at time of registration) on days 1 and 15 of 4-week cycles for up to 1 year, (avelumab not given cycle 1 day 1). A modified continual reassessment method will be used to determine dose de-escalation. The primary objective is to establish the safety of the combination and to determine the optimum dose of cetuximab. Secondary objectives include assessing evidence of antitumour activity by evaluating response rates and disease control rates at 6 and 12 months as well as progression-free and OS., Ethics and Dissemination: Approval granted by City and East REC (18/LO/0021). Findings will be published in peer-reviewed journals and disseminated at conferences., Trial Registration Number: NCT03494322., Competing Interests: Competing interests: MDF has received an institutional research grant and honoraria for consultancy from Merck.All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2023
Full Text: View/download PDF

27. Whole-genome sequencing of single circulating tumor cells from neuroendocrine neoplasms.

Author: Childs A, Steele CD, Vesely C, Rizzo FM, Ensell L, Lowe H, Dhami P, Vaikkinen H, Luong TV, Conde L, Herrero J, Caplin M, Toumpanakis C, Thirlwell C, Hartley JA, Pillay N, and Meyer T
Subjects: Biomarkers, Tumor genetics, DNA Copy Number Variations, Genomics, Humans, Whole Genome Sequencing, Neoplastic Cells, Circulating pathology, Neuroendocrine Tumors genetics
Abstract: Single-cell profiling of circulating tumor cells (CTCs) as part of a minimally invasive liquid biopsy presents an opportunity to characterize and monitor tumor heterogeneity and evolution in individual patients. In this study, we aimed to compare single-cell copy number variation (CNV) data with tissue and define the degree of intra- and inter-patient genomic heterogeneity. We performed next-generation sequencing (NGS) whole-genome CNV analysis of 125 single CTCs derived from seven patients with neuroendocrine neoplasms (NEN) alongside matched white blood cells (WBC), formalin-fixed paraffin-embedded (FFPE), and fresh frozen (FF) samples. CTC CNV profiling demonstrated recurrent chromosomal alterations in previously reported NEN copy number hotspots, including the prognostically relevant loss of chromosome 18. Unsupervised hierarchical clustering revealed CTCs with distinct clonal lineages as well as significant intra- and inter-patient genomic heterogeneity, including subclonal alterations not detectable by bulk analysis and previously unreported in NEN. Notably, we also demonstrated the presence of genomically distinct CTCs according to the enrichment strategy utilized (EpCAM-dependent vs size-based). This work has significant implications for the identification of therapeutic targets, tracking of evolutionary change, and the implementation of CTC-biomarkers in cancer.
Published: 2021
Full Text: View/download PDF

28. Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors.

Author: Mandair D, Khan MS, Lopes A, Furtado O'Mahony L, Ensell L, Lowe H, Hartley JA, Toumpanakis C, Caplin M, and Meyer T
Subjects: Adult, Aged, Aged, 80 and over, Biomarkers, Tumor analysis, Biomarkers, Tumor blood, Biomarkers, Tumor standards, Calibration, Cell Count standards, Female, Follow-Up Studies, Humans, Intestinal Neoplasms mortality, Intestinal Neoplasms pathology, Male, Middle Aged, Neoplasm Metastasis, Neuroendocrine Tumors mortality, Neuroendocrine Tumors pathology, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Prognosis, Reference Values, Stomach Neoplasms mortality, Stomach Neoplasms pathology, Survival Analysis, United Kingdom epidemiology, Young Adult, Intestinal Neoplasms diagnosis, Neoplastic Cells, Circulating pathology, Neuroendocrine Tumors diagnosis, Pancreatic Neoplasms diagnosis, Stomach Neoplasms diagnosis
Abstract: Background: Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined., Objective: This work aims to define optimal prognostic CTC thresholds in PanNET and midgut NETs., Patients and Methods: CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NETs (109). Patients were followed for progression-free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death., Results: The area under the receiver operating characteristic curve (AUROC) for progression at 12 months in PanNETs and midgut NETs identified the optimal CTC threshold as 1 or greater and 2 or greater, respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12-month progression with an odds ratio (OR) of 6.69 (P < .01) for PanNETs and 5.88 (P < .003) for midgut NETs. The same thresholds were found to be optimal for predicting death at 36 months, with an OR of 2.87 (P < .03) and 5.09 (P < .005) for PanNETs and midgut NETs, respectively. In multivariate Cox hazard regression analysis for PFS in PanNETs, 1 or greater CTC had a hazard ratio (HR) of 2.6 (P < .01), whereas 2 or greater CTCs had an HR of 2.25 (P < .01) in midgut NETs. In multivariate analysis OS in PanNETs, 1 or greater CTCs had an HR of 3.16 (P < .01) and in midgut NETs, 2 or greater CTCs had an HR of 1.73 (P < .06)., Conclusions: The optimal CTC threshold to predict PFS and OS in metastatic PanNETs and midgut NETs is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2021
Full Text: View/download PDF

29. Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours.

Author: Rizzo FM, Vesely C, Childs A, Marafioti T, Khan MS, Mandair D, Cives M, Ensell L, Lowe H, Akarca AU, Luong T, Caplin M, Toumpanakis C, Krell D, Thirlwell C, Silvestris F, Hartley JA, and Meyer T
Subjects: Adult, Biomarkers, Tumor blood, Bone Neoplasms genetics, Bone Neoplasms pathology, Bone Neoplasms secondary, Female, Gene Expression Regulation, Neoplastic genetics, Humans, Male, Middle Aged, Neoplastic Cells, Circulating pathology, Neuroendocrine Tumors genetics, Neuroendocrine Tumors pathology, Paraffin Embedding, Bone Neoplasms blood, Neoplastic Cells, Circulating metabolism, Neuroendocrine Tumors blood, Receptors, CXCR4 genetics
Abstract: Background: Bone metastases are associated with a worse outcome in patients with neuroendocrine tumours (NETs). Tumour overexpression of C-X-C chemokine receptor 4 (CXCR4) appears predictive of skeletal involvement. We investigated the role of circulating tumour cells (CTCs) and CXCR4 expression on CTCs as potential predictors of skeleton invasion., Methods: Blood from patients with metastatic bronchial, midgut or pancreatic NET (pNET) was analysed by CellSearch. CXCR4 immunohistochemistry was performed on matched formalin-fixed paraffin-embedded (FFPE) samples., Results: Two hundred and fifty-four patients were recruited with 121 midgut and 119 pNETs, of which 51 and 36% had detectable CTCs, respectively. Bone metastases were reported in 30% of midgut and 23% of pNET patients and were significantly associated with CTC presence (p = 0.003 and p < 0.0001). In a subgroup of 40 patients, 85% patients with CTCs had CTCs positive for CXCR4 expression. The proportion of CXCR4-positive CTCs in patients with bone metastases was 56% compared to 35% in those without (p = 0.18) it. Staining for CXCR4 on matched FFPE tissue showed a trend towards a correlation with CXCR4 expression on CTCs (p = 0.08)., Conclusions: CTC presence is associated with bone metastases in NETs. CXCR4 may be involved in CTC osteotropism and present a therapeutic target to reduce skeletal morbidity.
Published: 2019
Full Text: View/download PDF

30. Expression of somatostatin receptors 2 and 5 in circulating tumour cells from patients with neuroendocrine tumours.

Author: Childs A, Vesely C, Ensell L, Lowe H, Luong TV, Caplin ME, Toumpanakis C, Thirlwell C, Hartley JA, and Meyer T
Subjects: Humans, Neuroendocrine Tumors blood, Receptors, Somatostatin blood
Abstract: Background: Neuroendocrine tumours (NET) overexpress somatostatin receptors (SSTR) that can be targeted for therapy. Somatostatin receptor expression is routinely measured by molecular imaging but the resolution is insufficient to define heterogeneity. We hypothesised that SSTR expression could be measured on circulating tumour cells (CTCs) and used to investigate heterogeneity of expression and track changes during therapy., Methods: MCF-7 cells were transfected with SSTR2 or 5 and spiked into donor blood for analysis by CellSearch. Optimum anti-SSTR antibody concentration and exposure time were determined, and flow cytometry was used to evaluate assay sensitivity. For clinical evaluation, blood was analysed by CellSearch, and SSTR2/5 immunohistochemistry was performed on matched tissue samples., Results: Flow cytometry confirmed CellSearch was sensitive and that detection of SSTR was unaffected by the presence of somatostatin analogue up to a concentration of 100 ng ml -l . Thirty-one NET patients were recruited: grade; G1 (29%), G2 (45%), G3 (13%), primary site; midgut (58%), pancreatic (39%). Overall, 87% had SSTR-positive tumours according to somatostatin receptor scintigraphy or 68-Ga-DOTATE PET/CT. Circulating tumour cells were detected in 21 out of 31 patients (68%), of which 33% had evidence of heterogeneous expression of either SSTR2 (n=5) or SSTR5 (n=2)., Conclusions: Somatostatin receptors 2 and 5 are detectable on CTCs from NET patients and may be a useful biomarker for evaluating SSTR-targeted therapies and this is being prospectively evaluated in the Phase IV CALMNET trial (NCT02075606)., Competing Interests: TM has received research funding for this work from Ipsen, MEC has received grant funding and consultancy fees from Ipsen.
Published: 2016
Full Text: View/download PDF

31. Enumeration and Molecular Characterisation of Circulating Tumour Cells in Endometrial Cancer.

Author: Lemech CR, Ensell L, Paterson JC, Eminowicz G, Lowe H, Arora R, Arkenau HT, Widschwendter M, MacDonald N, Olaitan A, Mould T, Meyer T, Hartley J, Mitra A, Ledermann JA, McCormack M, and Kristeleit RS
Subjects: Aged, Aged, 80 and over, Carcinoma, Endometrioid blood, Carcinoma, Endometrioid metabolism, Carcinoma, Endometrioid pathology, Endometrial Neoplasms metabolism, Epithelial Cell Adhesion Molecule metabolism, Female, Humans, Immunohistochemistry, Middle Aged, Neoplasm Staging, Stathmin metabolism, Endometrial Neoplasms blood, Endometrial Neoplasms pathology, Neoplastic Cells, Circulating pathology
Abstract: Background: This is a feasibility study to determine whether circulating tumour cells (CTCs) are detectable and suitable for molecular profiling in advanced endometrial cancer (aEC)., Method: Between October 2012 and February 2014, 30 patients with aEC had baseline and up to 3 follow-up samples. CTCs and stathmin expression were evaluated using the CellSearch platform. Epithelial cell adhesion molecule (EpCAM) and stathmin immunohistochemistry were performed on FFPE tumour tissue., Results: Eighteen from 30 (60%) patients had detectable CTCs during study [1 CTC (n = 7), 2 (n = 4), 3 (n = 1), 4 (n = 2), 7 (n = 1), 8 (n = 1), 22 (n = 1), 172 (n = 1) in 7.5 ml blood]. Ten from 18 patients had between 50 and 100% of detectable CTCs that were stathmin positive. More CTC-positive than CTC-negative patients had non-endometrioid versus endometrioid histology, tumour size ≥5 versus <5 cm, higher-stage disease and worse survival [hazard ratio 3.3, p > 0.05, 95% confidence interval 0.7-16.2]. Twenty-one tumour blocks were tested for EpCAM and stathmin immunohistochemistry (IHC). Stathmin tumour immunostaining scores (TIS) on IHC were higher in CTC-positive patients., Conclusion: CTC enumeration and molecular profiling with stathmin on the CellSearch platform is feasible in aEC. Stathmin TIS on IHC, a known prognostic marker in EC, was associated with CTC positivity., (© 2016 S. Karger AG, Basel.)
Published: 2016
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

31 results on '"Ensell L"'

1. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

2. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

3. Body composition and lung cancer-associated cachexia in TRACERx

4. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

5. Genomic–transcriptomic evolution in lung cancer and metastasis

6. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

7. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

8. The evolution of lung cancer and impact of subclonal selection in TRACERx

9. SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2

10. SARS-CoV-2 evolution during treatment of chronic infection

11. P1460: SAFETY AND EFFICACY FINDINGS OF AUTO1, A FAST-OFF RATE CD19 CAR, IN RELAPSED/REFRACTORY PRIMARY CNS LYMPHOMA

12. P1459: SAFETY AND EFFICACY FINDINGS OF AUTO1, A FAST-OFF RATE CD19 CAR, IN RELAPSED/REFRACTORY B-CELL NON-HODGKIN’S LYMPHOMA (B-NHL), AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) / SMALL LYMPHOCYTIC LYMPHOMA (SLL)

13. Genomic reconstruction of the SARS-CoV-2 epidemic in England

14. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

15. 922P EACH: A phase II study evaluating the safety and anti-tumour activity of avelumab and cetuximab in recurrent/metastatic squamous cell carcinomas

16. A comparison of CellCollector with CellSearch in patients with neuroendocrine tumours

17. 2389 Detection of SSTR2 and 5 expression in circulating tumour cells from patients with neuroendocrine tumours

18. Genomic reconstruction of the SARS-CoV-2 epidemic in England

19. Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

20. Recurrent SARS-CoV-2 mutations in immunodeficient patients

21. SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2

22. COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: a prospective observational cohort study

23. The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis

24. Tracking SARS-CoV-2 mutations and variants through the COG-UK-Mutation Explorer

25. Spatial growth rate of emerging SARS-CoV-2 lineages in England, September 2020-December 2021

26. Protocol for the EACH trial: a multicentre phase II study evaluating the safety and antitumour activity of the combination of avelumab, an anti-PD-L1 agent, and cetuximab, as any line treatment for patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC) in the UK.

27. Whole-genome sequencing of single circulating tumor cells from neuroendocrine neoplasms.

28. Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors.

29. Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours.

30. Expression of somatostatin receptors 2 and 5 in circulating tumour cells from patients with neuroendocrine tumours.

31. Enumeration and Molecular Characterisation of Circulating Tumour Cells in Endometrial Cancer.

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

31 results on '"Ensell L"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources