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

Author

Baker, Stephen, Dougan, Gordon, Hess, Christoph, Kingston, Nathalie, Lehner, Paul J, Lyons, Paul A, Matheson, Nicholas J, Owehand, Willem H, Saunders, Caroline, Summers, Charlotte, Thaventhiran, James ED, Toshner, Mark, Weekes, Michael P, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J, Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Bergamaschi, Laura, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Lewis, Daniel, Marsden, Joe, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Richoz, Nathan, Romashova, Veronika, Yarkoni, Natalia Savinykh, Sharma, Rahul, Stefanucci, Luca, Stephens, Jonathan, Strezlecki, Mateusz, Turner, Lori, De Bie, Eckart MDD, Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Michael, Alice, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, di Stefano, Giovanni, Fahey, Codie, Michel, Rachel, and Bong, Sze-How

Subjects
Immunization, Pneumonia & Influenza, Lung, Prevention, Genetics, Vaccine Related, Biotechnology, Pneumonia, Emerging Infectious Diseases, Biodefense, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Adenosine Monophosphate, Aged, Alanine, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Chronic Disease, Evolution, Molecular, Genome, Viral, High-Throughput Nucleotide Sequencing, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Male, Mutagenesis, Mutant Proteins, Mutation, Phylogeny, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Time Factors, Viral Load, Virus Shedding, COVID-19 Drug Treatment, COVID-19 Serotherapy, CITIID-NIHR BioResource COVID-19 Collaboration, COVID-19 Genomics UK (COG-UK) Consortium, General Science & Technology
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

4. ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part I: Epidemiology, assessment of extrapulmonary conditions, candidate evaluation, selection criteria, and pathology statements

Author

Crespo, Maria M., Lease, Erika D., Sole, Amparo, Sandorfi, Nora, Snyder, Laurie D., Berry, Gerald J., Le Pavec, Jérôme, Venado, Aida E., Cifrian, Jose M., Goldberg, Hilary, Dilling, Daniel F., Gries, Cynthia, Nair, Arun, Willie, Keith, Meyer, Keith C., Shah, Rupal J., Tokman, Sofya, Holm, Are, Patterson, Caroline M., McWilliams, Tanya, Shtraichman, Osnat, Bemiss, Brad, Salgado, Juan, Farver, Carol, Strah, Heather, Wassilew, Katharina, Kaza, Vaidehi, Howsare, Molly, Murray, Michelle, Bhorade, Sangeeta, and Budev, Marie

Published
2021
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5. Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation

Author

Leard, Lorriana E., Holm, Are M., Valapour, Maryam, Glanville, Allan R., Attawar, Sandeep, Aversa, Meghan, Campos, Silvia V., Christon, Lillian M., Cypel, Marcelo, Dellgren, Göran, Hartwig, Matthew G., Kapnadak, Siddhartha G., Kolaitis, Nicholas A., Kotloff, Robert M., Patterson, Caroline M., Shlobin, Oksana A., Smith, Patrick J., Solé, Amparo, Solomon, Melinda, Weill, David, Wijsenbeek, Marlies S., Willemse, Brigitte W.M., Arcasoy, Selim M., and Ramos, Kathleen J.

Published
2021
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7. Novel approaches to the assessment of patients with chest symptoms in the acute medical and outpatient settings : the use of multislice computed tomography

Author

Patterson, Caroline Marie, Bell, Derek, and Padley, Simon

Subjects
610
Abstract

This thesis evaluated the clinical utility of cardiopulmonary computed tomography (CT) in patients presenting with chest pain and dyspnoea. Studies within this thesis confirmed the following. Firstly, there is a requirement for improved diagnostic pathways to minimise patients being discharged without a diagnosis, which currently occurs in 30-40% of patients admitted with chest pain and dyspnoea. Historically, CT has been utilised in 32% of admissions with chest pain and 10% of admissions with dyspnoea. Secondly, challenges exist to the wider adoption of cardiopulmonary CT. These include patient-related factors, institutional capabilities and guideline restrictions. In acute admissions, 11% of patients with dyspnoea and 7% of patients with chest pain and a low to moderate likelihood of CAD are suitable for CT. In the RACPC setting, including patients across the entire spectrum of CAD likelihood, 18% of patients are suitable for CT. NICE CG95 would recommend only 1% of acute chest pain admissions and 2% of RACPC attenders for CT. Thirdly, NICE CG95 would recommend 51% of acute chest pain admissions and 66% of RACPC attenders for discharge without cardiac investigation. In the RACPC population, significant CAD is identified in 10% of these patients and a major adverse cardiac event in 2%. Fourthly, in selected patients with suspected cardiac chest pain, cardiac CT has a diagnostic yield of 21% in acute admissions and 13% in RACPC attenders for significant CAD. In acute admissions with dyspnoea, cardiopulmonary CT has a diagnostic yield of 20% for CAD, 20% for pulmonary embolism, nil for aortic dissection and 89% for non-vascular chest pathology. Fifthly, inclusion of CT in diagnostic pathways for chest pain result in fewer patients discharged without a diagnosis, fewer invasive angiography procedures and reduced diagnostic costs. In patients with dyspnoea, CT provides value to clinicians making diagnoses and supports early discharge without detrimental outcomes.

Published
2016
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9. brat olympics

Author

Patterson, Caroline Ganci and Patterson, Caroline Ganci

Abstract

brat olympics is an exploration of feminine disgust, apprehension, and disorientation contextualized through interpersonal relationships and societal shapeshifting. It pays particular attention to gender performance, surburban queerness, and strangerness. The manuscript plays on the history of the bildungsroman, but instead of one consistent singular timeline, it provides three separate attempts at a characterization of a life. These disparate approaches to a singular life’s characterization stress the mundanity of documentation. This multinarrative approach satirizes the ideal of the singular confessional, and presents a discursive approach to the way we choose to build our worlds. Building off the works of the New Sentence language poets, brat olympics often teases at autobiographical concinnity and engages in play of the non sequitur and mosaic antics. Influences include Frank O’Hara, Ross Gay, Kim Addonizio, Ben Lerner, Joanna Fuhrmann, Eugene Ostashevsky, and Simone White, to name a few. Topics explored throughout the manuscript include but are not limited to: feminine domination, enforced male chastity, theatrics, snot, the wendy’s finger in the chili incident, endocannibalism, emotional projection on to the very topography of the mountainous west, the concept of the meal deal, suburban sprawl, and squirrel population management.

Published
2024

21. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Author

Collier, Dami A., Ferreira, Isabella A. T. M., Kotagiri, Prasanti, Datir, Rawlings P., Lim, Eleanor Y., Touizer, Emma, Meng, Bo, Abdullahi, Adam, Elmer, Anne, Kingston, Nathalie, Graves, Barbara, Le Gresley, Emma, Caputo, Daniela, Bergamaschi, Laura, Smith, Kenneth G. C., Bradley, John R., Ceron-Gutierrez, Lourdes, Cortes-Acevedo, Paulina, Barcenas-Morales, Gabriela, Linterman, Michelle A., McCoy, Laura E., Davis, Chris, Thomson, Emma, McKinney, Eoin, Doffinger, Rainer, Wills, Mark, Gupta, Ravindra K., Baker, Stephen, Dougan, Gordon, Hess, Christoph, Lehner, Paul J., Lyons, Paul A., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Maxwell, Patrick, Shaw, Ashley, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Krishna, Ben, Lewis, Daniel, Marsden, Joe, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Potts, Martin, Richoz, Nathan, Romashova, Veronika, Yarkoni, Natalia Savinykh, Sharma, Rahul, Stefanucci, Luca, Stephens, Jonathan, Strezlecki, Mateusz, Turner, Lori, D. D. De Bie, Eckart M., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Michael, Alice, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, Di Stefano, Giovanni, Fahey, Codie, Michel, Rachel, Bong, Sze-How, Coudert, Jerome D., Holmes, Elaine, Allison, John, Butcher, Helen, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Collier, Dami A. [0000-0001-5446-4423], Datir, Rawlings P. [0000-0003-0521-2144], Smith, Kenneth G. C. [0000-0003-3829-4326], Linterman, Michelle A. [0000-0001-6047-1996], McCoy, Laura E. [0000-0001-9503-7946], Thomson, Emma [0000-0003-1482-0889], Lyons, Paul A. [0000-0001-7035-8997], Gupta, Ravindra K. [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
article, 13/106, 38/39, 631/250/2152/2153/1291, 631/326/596/4130, 38
Abstract

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.

Published
2021
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22. Single-cell multi-omics analysis of the immune response in COVID-19

Author

Stephenson, Emily, Reynolds, Gary, Botting, Rachel A., Calero-Nieto, Fernando J., Morgan, Michael D., Tuong, Zewen Kelvin, Bach, Karsten, Sungnak, Waradon, Worlock, Kaylee B., Yoshida, Masahiro, Kumasaka, Natsuhiko, Kania, Katarzyna, Engelbert, Justin, Olabi, Bayanne, Spegarova, Jarmila Stremenova, Wilson, Nicola K., Mende, Nicole, Jardine, Laura, Gardner, Louis C. S., Goh, Issac, Horsfall, Dave, McGrath, Jim, Webb, Simone, Mather, Michael W., Lindeboom, Rik G. H., Dann, Emma, Huang, Ni, Polanski, Krzysztof, Prigmore, Elena, Gothe, Florian, Scott, Jonathan, Payne, Rebecca P., Baker, Kenneth F., Hanrath, Aidan T., Schim Van Der Loeff, Ina C. D., Barr, Andrew S., Sanchez-Gonzalez, Amada, Bergamaschi, Laura, Mescia, Federica, Barnes, Josephine L., Kilich, Eliz, De Wilton, Angus, Saigal, Anita, Saleh, Aarash, Janes, Sam M., Smith, Claire M., Gopee, Nusayhah, Wilson, Caroline, Coupland, Paul, Coxhead, Jonathan M., Kiselev, Vladimir Yu, Van Dongen, Stijn, Bacardit, Jaume, King, Hamish W., Rostron, Anthony J., Simpson, A. John, Hambleton, Sophie, Laurenti, Elisa, Lyons, Paul A., Meyer, Kerstin B., Nikolić, Marko Z., Duncan, Christopher J. A., Teichmann, Sarah A., Clatworthy, Menna R., Marioni, John C., Göttgens, Berthold, Haniffa, Muzlifah, Baker, Stephen, Bradley, John R., Dougan, Gordon, Goodfellow, Ian G., Gupta, Ravindra K., Hess, Christoph, Kingston, Nathalie, Lehner, Paul J., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Smith, Kenneth G. C., Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, De Sa, Aloka, Epping, Madeline, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Marsden, Jimmy, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Richoz, Nathan, Sharma, Rahul, Turner, Lori, De Bie, Eckart M. D. D., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Michael, Alice, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, Stefano, Giovanni Di, Allison, John, Butcher, Helen, Caputo, Daniela, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Graves, Barbara, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Gresley, Emma Le, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Calero-Nieto, Fernando J. [0000-0003-3358-8253], Morgan, Michael D. [0000-0003-0757-0711], Tuong, Zewen Kelvin [0000-0002-6735-6808], Sungnak, Waradon [0000-0002-0136-4960], Yoshida, Masahiro [0000-0002-3521-5322], Kumasaka, Natsuhiko [0000-0002-3557-0375], Spegarova, Jarmila Stremenova [0000-0002-0710-9266], Wilson, Nicola K. [0000-0003-0865-7333], Mende, Nicole [0000-0002-5078-2333], Gardner, Louis C. S. [0000-0002-7200-978X], Goh, Issac [0000-0002-6397-3518], Horsfall, Dave [0000-0002-8086-812X], Webb, Simone [0000-0003-3058-8952], Mather, Michael W. [0000-0001-7972-7111], Lindeboom, Rik G. H. [0000-0002-3660-504X], Dann, Emma [0000-0002-7400-7438], Polanski, Krzysztof [0000-0002-2586-9576], Payne, Rebecca P. [0000-0002-9037-7367], Baker, Kenneth F. [0000-0002-6735-2911], Schim van der Loeff, Ina C. D. [0000-0003-1196-6196], Barr, Andrew S. [0000-0002-8084-7644], Mescia, Federica [0000-0002-2759-4027], Barnes, Josephine L. [0000-0001-9938-3176], Janes, Sam M. [0000-0002-6634-5939], Smith, Claire M. [0000-0002-8913-0009], Coupland, Paul [0000-0002-2871-3374], Bacardit, Jaume [0000-0002-2692-7205], King, Hamish W. [0000-0001-5972-8926], Rostron, Anthony J. [0000-0002-9336-1723], Simpson, A. John [0000-0003-4731-7294], Hambleton, Sophie [0000-0001-7954-3267], Laurenti, Elisa [0000-0002-9917-9092], Lyons, Paul A. [0000-0001-7035-8997], Meyer, Kerstin B. [0000-0001-5906-1498], Nikolić, Marko Z. [0000-0001-6304-6848], Smith, Kenneth G. C. [0000-0003-3829-4326], Teichmann, Sarah A. [0000-0002-6294-6366], Clatworthy, Menna R. [0000-0002-3340-9828], Marioni, John C. [0000-0001-9092-0852], Göttgens, Berthold [0000-0001-6302-5705], Haniffa, Muzlifah [0000-0002-3927-2084], and Apollo - University of Cambridge Repository

Subjects
692/699/255/2514, 631/208/514/1949, article, 631/250/232, 631/250/254, 631/326/596/4130
Abstract

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255, Funder: University College London, Birkbeck MRC Doctoral Training Programme, Funder: The Jikei University School of Medicine, Funder: Action Medical Research (GN2779), Funder: NIHR Clinical Lectureship (CL-2017-01-004), Funder: NIHR (ACF-2018-01-004) and the BMA Foundation, Funder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194), Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944), Funder: Barbour Foundation, Funder: ERC Consolidator and EU MRG-Grammar awards, Funder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002), Funder: European Molecular Biology Laboratory (EMBL), Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

Published
2021
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24. Consensus document for the selection of lung transplant candidates:An update from the International Society for Heart and Lung Transplantation

Author

Leard, Lorriana E., Holm, Are M., Valapour, Maryam, Glanville, Allan R., Attawar, Sandeep, Aversa, Meghan, Campos, Silvia V., Christon, Lillian M., Cypel, Marcelo, Dellgren, Göran, Hartwig, Matthew G., Kapnadak, Siddhartha G., Kolaitis, Nicholas A., Kotloff, Robert M., Patterson, Caroline M., Shlobin, Oksana A., Smith, Patrick J., Solé, Amparo, Solomon, Melinda, Weill, David, Wijsenbeek, Marlies S., Willemse, Brigitte W.M., Arcasoy, Selim M., Ramos, Kathleen J., Leard, Lorriana E., Holm, Are M., Valapour, Maryam, Glanville, Allan R., Attawar, Sandeep, Aversa, Meghan, Campos, Silvia V., Christon, Lillian M., Cypel, Marcelo, Dellgren, Göran, Hartwig, Matthew G., Kapnadak, Siddhartha G., Kolaitis, Nicholas A., Kotloff, Robert M., Patterson, Caroline M., Shlobin, Oksana A., Smith, Patrick J., Solé, Amparo, Solomon, Melinda, Weill, David, Wijsenbeek, Marlies S., Willemse, Brigitte W.M., Arcasoy, Selim M., and Ramos, Kathleen J.

Abstract

Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.

Published
2021

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