@article{6fa1ebc80fa041988282128ae4b9c0d0,
title = "Alterations in T and B cell function persist in convalescent COVID-19 patients",
abstract = "Background: Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined. Methods: Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3–6 months of convalescence. Findings: We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8 + T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6 + B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10 + B cells was associated with the resolution of lung pathology. Conclusions: Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. Funding: Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving. ",
keywords = "B cells, COVID-19, T cells, Translation to patients, convalescent patients, long COVID, viral Infection, Cytokines, Interleukin-10, Humans, Interleukin-6, CD8-Positive T-Lymphocytes, SARS-CoV-2",
author = "Shuwa, {Halima Ali} and Tovah Shaw and Sean Knight and Kelly Wemyss and Flora Mcclure and Laurence Pearmain and Ian Prise and Christopher Jagger and David Morgan and Saba Khan and Oliver Brand and Elizabeth Mann and Andrew Ustianowski and {Diar Bakerly}, Nawar and Paul Dark and Brightling, {Christopher E} and Seema Brij and Timothy Felton and Angela Simpson and John Grainger and Tracy Hussell and Joanne Konkel and Madhvi Menon",
note = "Funding Information: This study was funded by the BBSRC ( BB/M025977/1 , to J.E.K. and BB/S01103X/1 , to T.N.S.), by the Lister Institute (Prize Fellowship to J.E.K.), by PTDF ( SHS/1327/18 , to H.A.S.), the Wellcome Trust ( 202865/Z/16/Z , to T.H.), The Kennedy Trust for Rheumatology Research (Rapid Response Award to J.R.G.), Versus Arthritis (F.A.M. and J.E.K. studentship), and philanthropy awards from 3M Global Giving (J.R.G. and T.H.) and the University of Manchester COVID-19 fund (J.E.K. and M.M.). J.R.G. is the recipient of a Senior Fellowship funded by The Kennedy Trust for Rheumatology Research . This work also was partly funded by UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC) . This report is independent research supported by the North West Lung Centre Charity and the NIHR Manchester Clinical Research Facility at Wythenshawe Hospital . We acknowledge the Manchester Allergy, Respiratory, and Thoracic Surgery Biobank and thank the study participants for their contribution. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. Angela Simpson, Tim Felton, Paul Dark, and Tracy Hussell are supported by the NIHR Manchester Biomedical Research Centre . In addition, we would like to thank the following for technical and scientific discussions: the Lydia Becker Institute of Immunology and Inflammation, the University of Manchester Flow Cytometry Facility, The NIHR Respiratory TRC, the UK Coronavirus Immunology Consortium, and PHOSP-COVID. Funding Information: This study was funded by the BBSRC (BB/M025977/1, to J.E.K. and BB/S01103X/1, to T.N.S.), by the Lister Institute (Prize Fellowship to J.E.K.), by PTDF (SHS/1327/18, to H.A.S.), the Wellcome Trust (202865/Z/16/Z, to T.H.), The Kennedy Trust for Rheumatology Research (Rapid Response Award to J.R.G.), Versus Arthritis (F.A.M. and J.E.K. studentship), and philanthropy awards from 3M Global Giving (J.R.G. and T.H.) and the University of Manchester COVID-19 fund (J.E.K. and M.M.). J.R.G. is the recipient of a Senior Fellowship funded by The Kennedy Trust for Rheumatology Research. This work also was partly funded by UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC). This report is independent research supported by the North West Lung Centre Charity and the NIHR Manchester Clinical Research Facility at Wythenshawe Hospital. We acknowledge the Manchester Allergy, Respiratory, and Thoracic Surgery Biobank and thank the study participants for their contribution. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. Angela Simpson, Tim Felton, Paul Dark, and Tracy Hussell are supported by the NIHR Manchester Biomedical Research Centre. In addition, we would like to thank the following for technical and scientific discussions: the Lydia Becker Institute of Immunology and Inflammation, the University of Manchester Flow Cytometry Facility, The NIHR Respiratory TRC, the UK Coronavirus Immunology Consortium, and PHOSP-COVID. Conceptualization, J.E.K. and M.M.; methodology, J.E.K. M.M. J.R.G. and T.H.; investigation, H.A.S. T.N.S. K.W. F.A.M. S.B.K. I.P. C.J. D.J.M. S.K. O.B. E.R.M. and the CIRCO investigators; formal analysis, I.P. and S.B.K.; resources, S.B.K. L.P. A.U. N.D.B. P.D. C.E.B. S.B. T.F. and A.S.; data curation, S.B.K.; writing ? original draft, J.E.K. and M.M.; writing ? review & editing, H.A.S. T.N.S. J.E.K. M.M. J.R.G. and T.H.; visualization, K.W.; supervision, J.E.K. and M.M.; funding acquisition, J.E.K. M.M. J.R.G. and T.H. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jun,
day = "11",
doi = "10.1016/j.medj.2021.03.013",
language = "English",
volume = "2",
pages = "720--+",
journal = "Med",
issn = "2666-6340",
publisher = "Cell Press",
number = "6",
}
