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.

SignificanceLoss of oral barrier homeostasis leads to the development of periodontitis, the most common chronic inflammatory condition of mankind. Therefore, it is important to better understand the immune mediators acting at this unique barrier to safeguard tissue integrity. Here we identify a vital role for γδ T cells in constraining pathological inflammation at the oral barrier, as the absence of γδ T cells resulted in enhanced pathology during periodontitis. We show that oral barrier γδ T cells produce the reparative cytokine Amphiregulin, administration of which rescued the elevated oral pathology of tcrδ−/− mice. Collectively, we identify a pathway controlling oral immunity mediated by barrier-resident γδ T cells, highlighting that these cells are crucial guards of oral barrier immune homeostasis.