Alterations in Phenotypes and Responses of T Cells Within 6 Months of Recovery from COVID-19: A Cohort Study

The COVID-19 pandemic,caused by the SARS-CoV-2 infection,is a global health crisis.While many patients have clinically recovered,little is known about long-term alterations in T cell responses of COVID-19 convalescents.In this study,T cell responses in peripheral blood mononuclear cells of a long-time COVID-19 clinically recovered(20–26 weeks)cohort(LCR)were measured via flow cytometry and ELISpot.The T cell responses of LCR were comparatively analyzed against an age and sex matched short-time clinically recovered(4–9 weeks)cohort(SCR)and a healthy donor cohort(HD).All volunteers were recruited from Wuhan Jinyintan Hospital,China.Phenotypic analysis showed that activation marker PD-1 expressing on CD4^(+)T cells of LCR was still significantly lower than that of HD.Functional analysis indicated that frequencies of Tc2,Th2 and Th17 in LCR were comparable to those of HD,but Tc17 was higher than that of HD.In LCR,compared to the HD,there were fewer IFN-c producing T cells but more IL-2 secreting T cells.In addition,the circulating Tfh cells in LCR were still slightly lower compared to HD,though the subsets composition had recovered.Remarkably,SARS-CoV-2 specific T cell responses in LCR were comparable to that of SCR.Collectively,T cell responses experienced long-term alterations in phenotype and functional potential of LCR cohort.However,after clinical recovery,SARS-CoV-2 specific T cell responses could be sustained at least for six months,which may be helpful in resisting re-infection。

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-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.