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

Shuwa, Halima A.; Shaw, Tovah N.; Knight, Sean B.; Wemyss, Kelly; McClure, Flora A.; Pearmain, Laurence; Prise, Ian; Jagger, Christopher; Morgan, David.J.; Khan, Saba; Brand, Oliver; Mann, Elizabeth R.; Ustianowski, Andrew; Bakerly, Nawar Diar; Dark, Paul; Brightling, Christopher E.; Brij, Seema; Felton, Timothy; Simpson, Angela; Grainger, John R.; Hussell, Tracy; Konkel, Joanne E.; Menon, Madhvi

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. Funding Provided by UKRI, Lister Institute of Preventative Medicine, The Wellcome Trust, The Kennedy Trust for Rheumatology Research and 3M Global Giving.