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

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Conclusions</h4>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.