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

摘要

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-γ^(+)),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-γ^(+)),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-γ,granzyme B and T-bet,the correlation between T-bet and IFN-γ 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.