Broad phenotypic alterations and potential dysfunction of lymphocytes in individuals clinically recovered from COVID-19

Although millions of patients have clinically recovered from COVID-19, little is known about the immune status of lymphocytes in these individuals. In this study, the peripheral blood mononuclear cells of a clinically recovered (CR) cohort were comparatively analyzed with those of an age- and sex-matched healthy donor cohort. We found that CD8(+) T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1 (IFN-gamma(+)), Tc2 (IL-4(+)), and Tc17 (IL-17A(+)) cell frequencies. The CD4(+) T cells of the CR cohort were decreased in frequency, especially the central memory T cell subset. Moreover, CD4(+) T cells in the CR cohort showed lower programmed cell death protein 1 (PD-1) expression and had lower frequencies of Th1 (IFN-gamma(+)), Th2 (IL-4(+)), Th17 (IL-17A(+)), and circulating follicular helper T (CXCR5(+) PD-1(+)) cells. Accordingly, the proportion of isotype-switched memory B cells (IgM(-) CD20(hi)) among B cells in the CR cohort showed a significantly lower proportion, although the level of the activation marker CD71 was elevated. For CD3(-)HLA-DR- lymphocytes in the CR cohort, in addition to lower levels of IFN-gamma, granzyme B and T-bet, the correlation between T-bet and IFN-gamma was not observed. Additionally, by taking into account the number of days after discharge, all the phenotypes associated with reduced function did not show a tendency toward recovery within 4-11 weeks. The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that severe acute respiratory syndrome coronavirus 2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery.