Long-Lasting Alterations in T and B Cell Function in Convalescent COVID-19 Patients

Abstract

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. Here we describe the phenotypic and functional characteristics of B and T cells in healthy individuals and individuals with acute or convalescent COVID-19. 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 long-term 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-10⁺ B cells was restored in a subset of convalescent patients, IL-6 production remained elevated. Our data are the first to define long-term alterations in the lymphocyte compartment of previously hospitalized COVID-19 patients, at up to 19 weeks of convalescence, and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes. We propose that alterations in B and T cell function following hospitalisation with COVID-19 could impact long-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients.

Funding: This study was funded by the BBSRC (BB/M025977/1 to JEK, BB/S01103X/1 to TNS), by the Lister Institute (Prize Fellowship to JEK), by PTDF (SHS/1327/18 to HAS), The Wellcome Trust (202865/Z/16/Z to TH), The Kennedy Trust for Rheumatology Research (Rapid Response Award to JRG) and Versus Arthritis (FAM and JEK studentship). 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 for supporting this project and thank the study participants for their contribution.

Ethical Approval: Ethical approval obtained from the National Research Ethics Service (REC reference 15/NW/0409 for ManARTS and 18/WA/0368 for NCARC). Informed consent was obtained from each patient, clinical information was extracted from written/electronic medical records including demographic data, presenting symptoms, comorbidities, radiographic findings, vital signs, and laboratory data.

Declaration of Interest: None to declare.

Keywords: lymphocytes, B cells, T cells, COVID-19, SARS-CoV-2, lung, respiratory infection, inflammation, long COVID, convalescent, mucosal, immune response