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3. Genomic investigations of unexplained acute hepatitis in children

Author

Morfopoulou, Sofia, Buddle, Sarah, Torres Montaguth, Oscar Enrique, Atkinson, Laura, Guerra-Assunção, José Afonso, Moradi Marjaneh, Mahdi, Zennezini Chiozzi, Riccardo, Storey, Nathaniel, Campos, Luis, Hutchinson, J. Ciaran, Counsell, John R., Pollara, Gabriele, Roy, Sunando, Venturini, Cristina, Antinao Diaz, Juan F., Siam, Ala’a, Tappouni, Luke J., Asgarian, Zeinab, Ng, Joanne, Hanlon, Killian S., Lennon, Alexander, McArdle, Andrew, Czap, Agata, Rosenheim, Joshua, Andrade, Catarina, Anderson, Glenn, Lee, Jack C. D., Williams, Rachel, Williams, Charlotte A., Tutill, Helena, Bayzid, Nadua, Martin Bernal, Luz Marina, Macpherson, Hannah, Montgomery, Kylie-Ann, Moore, Catherine, Templeton, Kate, Neill, Claire, Holden, Matt, Gunson, Rory, Shepherd, Samantha J., Shah, Priyen, Cooray, Samantha, Voice, Marie, Steele, Michael, Fink, Colin, Whittaker, Thomas E., Santilli, Giorgia, Gissen, Paul, Kaufer, Benedikt B., Reich, Jana, Andreani, Julien, Simmonds, Peter, Alrabiah, Dimah K., Castellano, Sergi, Chikowore, Primrose, Odam, Miranda, Rampling, Tommy, Houlihan, Catherine, Hoschler, Katja, Talts, Tiina, Celma, Cristina, Gonzalez, Suam, Gallagher, Eileen, Simmons, Ruth, Watson, Conall, Mandal, Sema, Zambon, Maria, Chand, Meera, Hatcher, James, De, Surjo, Baillie, Kenneth, Semple, Malcolm Gracie, Martin, Joanne, Ushiro-Lumb, Ines, Noursadeghi, Mahdad, Deheragoda, Maesha, Hadzic, Nedim, Grammatikopoulos, Tassos, Brown, Rachel, Kelgeri, Chayarani, Thalassinos, Konstantinos, Waddington, Simon N., Jacques, Thomas S., Thomson, Emma, Levin, Michael, Brown, Julianne R., and Breuer, Judith

Published
2023
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4. Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

Author

Chandran, Aneesh, Rosenheim, Joshua, Nageswaran, Gayathri, Swadling, Leo, Pollara, Gabriele, Gupta, Rishi K., Burton, Alice R., Guerra-Assunção, José Afonso, Woolston, Annemarie, Ronel, Tahel, Pade, Corinna, Gibbons, Joseph M., Sanz-Magallon Duque De Estrada, Blanca, Robert de Massy, Marc, Whelan, Matthew, Semper, Amanda, Brooks, Tim, Altmann, Daniel M., Boyton, Rosemary J., McKnight, Áine, Captur, Gabriella, Manisty, Charlotte, Treibel, Thomas Alexander, Moon, James C., Tomlinson, Gillian S., Maini, Mala K., Chain, Benjamin M., and Noursadeghi, Mahdad

Published
2022
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5. The CSF transcriptome in pneumococcal meningitis reveals compartmentalised host inflammatory responses associated with mortality.

Author

Guerra-Assuncao, Jose-Afonso, primary, Chakroborty, Probir, additional, Pollara, Gabriele, additional, Venturini, Cristina, additional, Mlozowa, Veronica S, additional, Denis, Brigitte, additional, Nyirenda, Mulinda, additional, Lalloo, David G, additional, Noursadeghi, Mahad, additional, Heyderman, Robert S, additional, Brown, Jeremy S, additional, and Wall, Emma C, additional

Published
2024
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7. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Author

Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Altmann, Daniel M, Amin, Oliver E, Andiapen, Mervyn, Artico, Jessica, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, Bhuva, Anish N, Boulter, Alex, Bowles, Ruth, Boyton, Rosemary J, Bracken, Olivia V, O'Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K, Captur, Gabriella, Champion, Nicola, Chan, Carmen, Chandran, Aneesh, Collier, David, Couto de Sousa, Jorge, Couto-Parada, Xose, Cutino-Moguel, Teresa, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hewson, Jacqueline, Hickling, Lauren M, Hingorani, Aroon D, Howes, Lee, Hughes, Alun, Hughes, Gemma, Hughes, Rebecca, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Joy, George, Kapil, Vikas, Kurdi, Hibba, Lambourne, Jonathan, Lin, Kai-Min, Louth, Sarah, Maini, Mala K, Mandadapu, Vineela, Manisty, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon, James C, Munoz Sandoval, Diana, Murray, Sam M, Noursadeghi, Mahdad, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Rosenheim, Joshua, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel, Thomas, Stephen, Thornton, George D, Treibel, Thomas A, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Gupta, Rishi K, Bell, Lucy C, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, McKnight, Aine, and Chain, Benjamin M

Published
2021
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16. Functional consequences of HSV-1 infection of dendritic cells

Author

Pollara, Gabriele

Subjects
616.522
Abstract

Herpes simplex virus-1 (HSV-1) infects a significant proportion of the population, causing widespread morbidity and occasional mortality. An understanding of the interaction of this virus with the immune system will aid in the development of vaccines to reduce the prevalence of this infection, and in evaluating its potential role as a vector in immunotherapy. Dendritic cells (DC) are the critical initiators of adaptive immune responses to HSV-1 and are likely to encounter the virus early after infection of the skin or mucosa. This thesis aims to describe the functional consequences of the interaction between HSV-1 and DC. DCs are readily infected by HSV-1. The function of these cells is affected in a multitude of ways. The capacity of infected DC to stimulate T cell proliferation is reduced, following changes in morphology, IL-12 secretion and surface phenotype. However, the infection of DC by HSV-1 also results in activation of both infected and uninfected cells. The secretion and paracrine activity of type IIFN is responsible for the activation of bystander DC and plays an important amplifying role in the secretion of IL-12 by these cells. In contrast, HSV-1 envelope structures bind to the surface of DC and induce maturation directly. The binding of HSV-1 glycoprotein D is critical to the acquisition of this mature phenotype. In the context of natural HSV-1 infection, these findings suggest the hypothesis that the coupling of viral entry to the activation of DC signalling pathways is counterbalanced by viral disruption of DC maturation. This delays the generation of the immune responses to HSV-1. Nonetheless, the parallel release of type I IFN, resulting in paracrine activation, enables other DC to mount an antiviral immune response.

Published
2005

17. Dysfunctional effector memory CD8 T cells in the bronchoalveolar compartment of people living with HIV

Author

Mthembu, Maphe, primary, Claassen, Helgard, additional, Khuzwayo, Sharon, additional, Voillet, Valentin, additional, Naidoo, Anneta, additional, Nyamande, Kennedy, additional, Khan, Dilshaad F., additional, Maharaj, Priya, additional, Mitha, Mohammed, additional, Mhlane, Zoey, additional, Karim, Farina, additional, Andersen-Nissen, Erica, additional, Ndung’u, Thumbi, additional, Pollara, Gabriele, additional, and Wong, Emily B., additional

Published
2023
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19. Genomic investigations of unexplained acute hepatitis in children

Author

Morfopoulou, Sofia; https://orcid.org/0000-0001-8181-4548, Buddle, Sarah; https://orcid.org/0000-0002-4738-9469, Montaguth, Oscar Enrique Torres, Atkinson, Laura, Guerra-Assunção, José Afonso; https://orcid.org/0000-0001-6593-403X, Marjaneh, Mahdi Moradi; https://orcid.org/0000-0002-9412-9029, Chiozzi, Riccardo Zenezini, Storey, Nathaniel; https://orcid.org/0000-0001-5942-4674, Campos, Luis; https://orcid.org/0000-0002-4317-0013, Hutchinson, J Ciaran, Counsell, John R; https://orcid.org/0000-0001-9208-101X, Pollara, Gabriele; https://orcid.org/0000-0001-5772-0322, Roy, Sunando, Venturini, Cristina, Antinao Diaz, Juan F, Siam, Ala'a, Tappouni, Luke J; https://orcid.org/0000-0003-2397-0512, Asgarian, Zeinab, Ng, Joanne, Hanlon, Killian S, Lennon, Alexander; https://orcid.org/0000-0002-3363-0637, McArdle, Andrew; https://orcid.org/0000-0001-7448-0869, Czap, Agata, Rosenheim, Joshua; https://orcid.org/0000-0003-0171-2053, Andrade, Catarina, Anderson, Glenn, Lee, Jack C D; https://orcid.org/0000-0002-9866-2808, Williams, Rachel, Williams, Charlotte A, Tutill, Helena; https://orcid.org/0000-0002-9977-9012, et al, Morfopoulou, Sofia; https://orcid.org/0000-0001-8181-4548, Buddle, Sarah; https://orcid.org/0000-0002-4738-9469, Montaguth, Oscar Enrique Torres, Atkinson, Laura, Guerra-Assunção, José Afonso; https://orcid.org/0000-0001-6593-403X, Marjaneh, Mahdi Moradi; https://orcid.org/0000-0002-9412-9029, Chiozzi, Riccardo Zenezini, Storey, Nathaniel; https://orcid.org/0000-0001-5942-4674, Campos, Luis; https://orcid.org/0000-0002-4317-0013, Hutchinson, J Ciaran, Counsell, John R; https://orcid.org/0000-0001-9208-101X, Pollara, Gabriele; https://orcid.org/0000-0001-5772-0322, Roy, Sunando, Venturini, Cristina, Antinao Diaz, Juan F, Siam, Ala'a, Tappouni, Luke J; https://orcid.org/0000-0003-2397-0512, Asgarian, Zeinab, Ng, Joanne, Hanlon, Killian S, Lennon, Alexander; https://orcid.org/0000-0002-3363-0637, McArdle, Andrew; https://orcid.org/0000-0001-7448-0869, Czap, Agata, Rosenheim, Joshua; https://orcid.org/0000-0003-0171-2053, Andrade, Catarina, Anderson, Glenn, Lee, Jack C D; https://orcid.org/0000-0002-9866-2808, Williams, Rachel, Williams, Charlotte A, Tutill, Helena; https://orcid.org/0000-0002-9977-9012, and et al

Abstract

Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK. Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells. Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

Published
2023

20. Altered IL-6 signalling and risk of tuberculosis disease: a meta-analysis and Mendelian randomisation study

Author

Hamilton, Fergus, Schurz, Haiko, Yates, Tom A., Gilchrist, James J., Möller, Marlo, Naranbhai, Vivek, Ghazal, Peter, Timpson, Nicholas J, Parks, Tom, and Pollara, Gabriele

Subjects
Article
Abstract

SummaryIL-6 responses are ubiquitous inMycobacterium tuberculosis (Mtb)infections, but their role in determining human tuberculosis (TB) disease risk is unknown. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor(IL6R)gene, focusing on the non-synonymous variant, rs2228145, associated with reduced classical IL-6 signalling, to assess the effect of altered IL-6 activity on TB disease risk. We identified 16 genome wide association studies (GWAS) of TB disease collating 17,982 cases of TB disease and 972,389 controls across 4 continents. Meta-analyses and Mendelian randomisation analyses revealed that reduced classical IL-6 signalling was associated with lower odds of TB disease, a finding replicated using multiple, independent SNP instruments and 2 separate exposure variables. Our findings establish a causal relationship between IL-6 signalling and the outcome ofMtbinfection, suggesting IL-6 antagonists do not increase the risk of TB disease and should be investigated as adjuncts in treatment.

Published
2023

23. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Author

Gupta, Rishi K, primary, Rosenheim, Joshua, additional, Bell, Lucy C, additional, Chandran, Aneesh, additional, Guerra-Assuncao, Jose A, additional, Pollara, Gabriele, additional, Whelan, Matthew, additional, Artico, Jessica, additional, Joy, George, additional, Kurdi, Hibba, additional, Altmann, Daniel M, additional, Boyton, Rosemary J, additional, Maini, Mala K, additional, McKnight, Aine, additional, Lambourne, Jonathan, additional, Cutino-Moguel, Teresa, additional, Manisty, Charlotte, additional, Treibel, Thomas A, additional, Moon, James C, additional, Chain, Benjamin M, additional, Noursadeghi, Mahdad, additional, Abbass, Hakam, additional, Abiodun, Aderonke, additional, Alfarih, Mashael, additional, Alldis, Zoe, additional, Amin, Oliver E, additional, Andiapen, Mervyn, additional, Augusto, João B, additional, Baca, Georgiana L, additional, Bailey, Sasha NL, additional, Bhuva, Anish N, additional, Boulter, Alex, additional, Bowles, Ruth, additional, Bracken, Olivia V, additional, O'Brien, Ben, additional, Brooks, Tim, additional, Bullock, Natalie, additional, Butler, David K, additional, Captur, Gabriella, additional, Champion, Nicola, additional, Chan, Carmen, additional, Collier, David, additional, Couto de Sousa, Jorge, additional, Couto-Parada, Xose, additional, Davies, Rhodri H, additional, Douglas, Brooke, additional, Di Genova, Cecilia, additional, Dieobi-Anene, Keenan, additional, Diniz, Mariana O, additional, Ellis, Anaya, additional, Feehan, Karen, additional, Finlay, Malcolm, additional, Fontana, Marianna, additional, Forooghi, Nasim, additional, Gaier, Celia, additional, Gibbons, Joseph M, additional, Gilroy, Derek, additional, Hamblin, Matt, additional, Harker, Gabrielle, additional, Hewson, Jacqueline, additional, Hickling, Lauren M, additional, Hingorani, Aroon D, additional, Howes, Lee, additional, Hughes, Alun, additional, Hughes, Gemma, additional, Hughes, Rebecca, additional, Itua, Ivie, additional, Jardim, Victor, additional, Lee, Wing-Yiu Jason, additional, Jensen, Melaniepetra, additional, Jones, Jessica, additional, Jones, Meleri, additional, Kapil, Vikas, additional, Lin, Kai-Min, additional, Louth, Sarah, additional, Mandadapu, Vineela, additional, Manisty,, Charlotte, additional, McKnight, Áine, additional, Menacho, Katia, additional, Mfuko, Celina, additional, Mitchelmore, Oliver, additional, Moon, Christopher, additional, Moon,, James C, additional, Munoz Sandoval, Diana, additional, Murray, Sam M, additional, Otter, Ashley, additional, Pade, Corinna, additional, Palma, Susana, additional, Parker, Ruth, additional, Patel, Kush, additional, Pawarova, Babita, additional, Petersen, Steffen E, additional, Piniera, Brian, additional, Pieper, Franziska P, additional, Pope, Daniel, additional, Prossora, Maria, additional, Rannigan, Lisa, additional, Rapala, Alicja, additional, Reynolds, Catherine J, additional, Richards, Amy, additional, Robathan, Matthew, additional, Sambile, Genine, additional, Schmidt, Nathalie M, additional, Semper, Amanda, additional, Seraphim, Andreas, additional, Simion, Mihaela, additional, Smit, Angelique, additional, Sugimoto, Michelle, additional, Swadling, Leo, additional, Taylor, Stephen, additional, Temperton, Nigel, additional, Thomas, Stephen, additional, Thornton, George D, additional, Tucker, Art, additional, Veerapen, Jessry, additional, Vijayakumar, Mohit, additional, Welch, Sophie, additional, Wodehouse, Theresa, additional, Wynne, Lucinda, additional, and Zahedi, Dan, additional

Published
2021
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24. C-reactive protein-guided use of procalcitonin in COVID-19

Author

Houghton, Rebecca, primary, Moore, Nathan, additional, Williams, Rebecca, additional, El-Bakri, Fatima, additional, Peters, Jonathan, additional, Mori, Matilde, additional, Vernet, Gabrielle, additional, Lynch, Jessica, additional, Lewis, Henry, additional, Tavener, Maryanna, additional, Durham, Tom, additional, Bowyer, Jack, additional, Saeed, Kordo, additional, and Pollara, Gabriele, additional

Published
2021
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27. Preserved C-reactive protein responses to blood stream infections following tocilizumab treatment for COVID-19

Author

Wey, Emmanuel Q., primary, Bristow, Clare, additional, Nandani, Aarti, additional, O'Farrell, Bryan, additional, Pang, Jay, additional, Lanzman, Marisa, additional, Yang, Shuang, additional, Ho, Soo, additional, Mack, Damien, additional, Spiro, Michael, additional, Balakrishnan, Indran, additional, Bhagani, Sanjay, additional, and Pollara, Gabriele, additional

Published
2021
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28. Preserved C-reactive protein responses to blood stream infections following tocilizumab treatment for COVID-19

Author

Wey, Emmanuel Q, primary, Bristow, Clare, additional, Nandani, Aarti, additional, O’Farrell, Bryan, additional, Pang, Jay, additional, Lanzman, Marisa, additional, Yang, Shuang, additional, Ho, Soo, additional, Mack, Damien, additional, Spiro, Michael, additional, Balakrishnan, Indran, additional, Bhagani, Sanjay, additional, and Pollara, Gabriele, additional

Published
2021
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29. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Author

Gupta, Rishi K, Rosenheim, Joshua, Bell, Lucy C, Chandran, Aneesh, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, Artico, Jessica, Joy, George, Kurdi, Hibba, Altmann, Daniel M, Boyton, Rosemary J, Maini, Mala K, McKnight, Aine, Lambourne, Jonathan, Cutino-Moguel, Teresa, Manisty, Charlotte, Treibel, Thomas A, Moon, James C, Chain, Benjamin M, Noursadeghi, Mahdad, Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E, Andiapen, Mervyn, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, Bhuva, Anish N, Boulter, Alex, Bowles, Ruth, Bracken, Olivia V, O'Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K, Captur, Gabriella, Champion, Nicola, Chan, Carmen, Collier, David, Couto de Sousa, Jorge, Couto-Parada, Xose, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hewson, Jacqueline, Hickling, Lauren M, Hingorani, Aroon D, Howes, Lee, Hughes, Alun, Hughes, Gemma, Hughes, Rebecca, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, Manisty,, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon,, James C, Munoz Sandoval, Diana, Murray, Sam M, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, Zahedi, Dan, Gupta, Rishi K, Rosenheim, Joshua, Bell, Lucy C, Chandran, Aneesh, Guerra-Assuncao, Jose A, Pollara, Gabriele, Whelan, Matthew, Artico, Jessica, Joy, George, Kurdi, Hibba, Altmann, Daniel M, Boyton, Rosemary J, Maini, Mala K, McKnight, Aine, Lambourne, Jonathan, Cutino-Moguel, Teresa, Manisty, Charlotte, Treibel, Thomas A, Moon, James C, Chain, Benjamin M, Noursadeghi, Mahdad, Abbass, Hakam, Abiodun, Aderonke, Alfarih, Mashael, Alldis, Zoe, Amin, Oliver E, Andiapen, Mervyn, Augusto, João B, Baca, Georgiana L, Bailey, Sasha NL, Bhuva, Anish N, Boulter, Alex, Bowles, Ruth, Bracken, Olivia V, O'Brien, Ben, Brooks, Tim, Bullock, Natalie, Butler, David K, Captur, Gabriella, Champion, Nicola, Chan, Carmen, Collier, David, Couto de Sousa, Jorge, Couto-Parada, Xose, Davies, Rhodri H, Douglas, Brooke, Di Genova, Cecilia, Dieobi-Anene, Keenan, Diniz, Mariana O, Ellis, Anaya, Feehan, Karen, Finlay, Malcolm, Fontana, Marianna, Forooghi, Nasim, Gaier, Celia, Gibbons, Joseph M, Gilroy, Derek, Hamblin, Matt, Harker, Gabrielle, Hewson, Jacqueline, Hickling, Lauren M, Hingorani, Aroon D, Howes, Lee, Hughes, Alun, Hughes, Gemma, Hughes, Rebecca, Itua, Ivie, Jardim, Victor, Lee, Wing-Yiu Jason, Jensen, Melaniepetra, Jones, Jessica, Jones, Meleri, Kapil, Vikas, Lin, Kai-Min, Louth, Sarah, Mandadapu, Vineela, Manisty,, Charlotte, McKnight, Áine, Menacho, Katia, Mfuko, Celina, Mitchelmore, Oliver, Moon, Christopher, Moon,, James C, Munoz Sandoval, Diana, Murray, Sam M, Otter, Ashley, Pade, Corinna, Palma, Susana, Parker, Ruth, Patel, Kush, Pawarova, Babita, Petersen, Steffen E, Piniera, Brian, Pieper, Franziska P, Pope, Daniel, Prossora, Maria, Rannigan, Lisa, Rapala, Alicja, Reynolds, Catherine J, Richards, Amy, Robathan, Matthew, Sambile, Genine, Schmidt, Nathalie M, Semper, Amanda, Seraphim, Andreas, Simion, Mihaela, Smit, Angelique, Sugimoto, Michelle, Swadling, Leo, Taylor, Stephen, Temperton, Nigel J., Thomas, Stephen, Thornton, George D, Tucker, Art, Veerapen, Jessry, Vijayakumar, Mohit, Welch, Sophie, Wodehouse, Theresa, Wynne, Lucinda, and Zahedi, Dan

Abstract

Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive part

Published
2021

30. Vitamin D3replacement enhances antigen-specific immunity in older adults

Author

Chambers, Emma S., Vukmanovic-Stejic, Milica, Turner, Carolin T., Shih, Barbara B., Trahair, Hugh, Pollara, Gabriele, Tsaliki, Evdokia, Rustin, Malcolm, Freeman, Tom C., Mabbott, Neil A., Noursadeghi, Mahdad, Martineau, Adrian R., Akbar, Arne N., Chambers, Emma S., Vukmanovic-Stejic, Milica, Turner, Carolin T., Shih, Barbara B., Trahair, Hugh, Pollara, Gabriele, Tsaliki, Evdokia, Rustin, Malcolm, Freeman, Tom C., Mabbott, Neil A., Noursadeghi, Mahdad, Martineau, Adrian R., and Akbar, Arne N.

Abstract

Introduction: Ageing is associated with increased number of infections, decreased vaccine efficacy and increased systemic inflammation termed inflammageing. These changes are reflected by reduced recall responses to varicella zoster virus (VZV) challenge in the skin of older adults. Vitamin D deficiency is more common in the old and has been associated with frailty and increased inflammation. In addition, vitamin D increases immunoregulatory mechanisms and therefore has the potential to inhibit inflammageing. Objectives: We investigated the use of vitamin D3 replacement to enhance cutaneous antigen-specific immunity in older adults (≥65 years). Methods: Vitamin D insufficient older adults (n = 18) were administered 6400IU of vitamin D3/day orally for 14 weeks. Antigen-specific immunity to VZV was assessed by clinical score assessment of the injection site and transcriptional analysis of skin biopsies collected from challenged injection sites pre- and post-vitamin D3 replacement. Results: We showed that older adults had reduced VZV-specific cutaneous immune response and increased non-specific inflammation as compared to young. Increased non-specific inflammation observed in the skin of older adults negatively correlated with vitamin D sufficiency. We showed that vitamin D3 supplementation significantly increased the response to cutaneous VZV antigen challenge in older adults. This enhancement was associated with a reduction in inflammatory monocyte infiltration with a concomitant enhancement of T cell recruitment to the site of antigen challenge in the skin. Conclusion: Vitamin D3 replacement can boost antigen-specific immunity in older adults with sub-optimal vitamin D status.

Published
2021

31. Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease

Author

Pollara, Gabriele, primary, Turner, Carolin T., additional, Rosenheim, Joshua, additional, Chandran, Aneesh, additional, Bell, Lucy C. K., additional, Khan, Ayesha, additional, Patel, Amit, additional, Peralta, Luis Felipe, additional, Folino, Anna, additional, Akarca, Ayse, additional, Venturini, Cristina, additional, Baker, Tina, additional, Ecker, Simone, additional, Ricciardolo, Fabio L. M., additional, Marafioti, Teresa, additional, Ugarte-Gil, Cesar, additional, Moore, David A. J., additional, Chain, Benjamin M., additional, Tomlinson, Gillian S., additional, and Noursadeghi, Mahdad, additional

Published
2021
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35. Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection

Author

Gupta, Rishi K., primary, Rosenheim, Joshua, additional, Bell, Lucy C., additional, Chandran, Aneesh, additional, Guerra-Assuncao, Jose A., additional, Pollara, Gabriele, additional, Whelan, Matthew, additional, Artico, Jessica, additional, Joy, George, additional, Kurdi, Hibba, additional, Altmann, Daniel M., additional, Boyton, Rosemary, additional, Maini, Mala, additional, McKnight, Aine, additional, Lambourne, Jonathan, additional, Cutino-moguel, Teresa, additional, Manisty, Charlotte, additional, Treibel, Thomas A., additional, Moon, James C, additional, Chain, Benjamin, additional, and Noursadeghi, Mahdad, additional

Published
2021
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38. Vitamin D3 replacement enhances antigen-specific immunity in older adults

Author

Chambers, Emma S, primary, Vukmanovic-Stejic, Milica, additional, Turner, Carolin T, additional, Shih, Barbara B, additional, Trahair, Hugh, additional, Pollara, Gabriele, additional, Tsaliki, Evdokia, additional, Rustin, Malcolm, additional, Freeman, Tom C, additional, Mabbott, Neil A, additional, Noursadeghi, Mahdad, additional, Martineau, Adrian R, additional, and Akbar, Arne N, additional

Published
2020
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50. Intravenous catheter-related adverse events exceed drug-related adverse events in outpatient parenteral antimicrobial therapy

Author

Underwood, Jonathan, Marks, Michael, Collins, Steve, Logan, Sarah, and Pollara, Gabriele

Abstract

Background\ud\udDrug-related adverse events (AEs) are reported to be common amongst patients receiving outpatient parenteral antimicrobial therapy (OPAT). However, comparative data regarding intravenous (iv) catheter-related AEs are lacking.\ud\ud\udObjectives\ud\udTo compare drug- and iv catheter-related AEs from a large UK OPAT centre.\ud\ud\udPatients and methods\ud\udWe reviewed 544 OPAT episodes [median (IQR) age: 57 (39–71) years, 60% male, 13% with diabetes] with a median (IQR) duration of 7 (2–18) days. Clinically significant drug- and iv catheter-related AEs were calculated as a percentage of OPAT episodes with an AE and also as AEs per 1000 iv drug/catheter days.\ud\ud\udResults\ud\udDrug-related AEs complicated 13 (2.4%) OPAT episodes at 1.7 (95% CI 0.9–2.9) per 1000 drug days. Catheter-related AEs occurred more frequently, complicating 32 (5.9%) episodes at 5.7 (95% CI 4.2–7.9) per 1000 iv catheter days (χ2 test for difference in AE rate: P

Published
2018

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