Alterations in T and B cell function persist in convalescent COVID-19 patients

10.1016/j.medj.2021.03.013

Med

7th April 2021

Contributing to research themes:

Abstract

Background: Emerging studies indicate that some 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 hospitalised 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 programme evident in CD8+ T cells as well as elevated production of type-1 cytokines and 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 towards a pro-inflammatory phenotype. Whereas the frequency of IL-6+ B cells was restored in convalescent patients irrespective of clinical outcome, recovery of IL-10+ B cells was associated with 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 one subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalisation with COVID-19 could impact longer term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients.

Author list:

#Contributed equally

†Joint senior authors

 

Author Affiliations

1) Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK

2) Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Ashworth Laboratories, Edinburgh, EH9 3FL, UK

3) Department of Respiratory Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK

4) Wellcome Trust Centre for Cell Matrix Research, The University of Manchester, Manchester, M13 9PT, UK

5) Division of Infection, Immunity and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, UK

6) Maternal and Fetal Health Centre, Division of Developmental Biology, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, 5th Floor St. Mary’s Hospital, Oxford Road, Manchester M13 9WL, UK

7) Regional Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK

8) Department of Respiratory Sciences, University of Leicester, Leicester, LE3 9QP, UK

9) Department of Respiratory Medicine, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, UK

Halima A.Shuwa1,#, Tovah N.Shaw1,2,#, Sean B.Knight1,3, Kelly Wemyss1, Flora A.McClure1, Laurence Pearmain4,5, Ian Prise1, Christopher Jagger1, David.J. Morgan1, Saba Khan1, Oliver Brand1, Elizabeth R.Mann1,6, Andrew Ustianowski1,5, Nawar Diar Bakerly3, Paul Dark7, Christopher E.Brightling8, Seema Brij9, CIRCO, Timothy Felton5 , Angela Simpson5, John R.Grainger1,†, Tracy Hussell1,†, Joanne E.Konkel1†, Madhvi Menon1,†