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

Abstract

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.

A single dose of COVID-19 vaccine induces a strong T cell and B cell response in healthcare professionals recovered from SARS-CoV-2 infection

“…According to our results, recovered participants (at T1) displayed profound alterations in the proportion of circulating Tfh cells, as well as in their activation status, functional compartment distribution and polarization, even 6 months after SARS-CoV-2 infection onset, when compared to the basal levels evaluated in naive-infection donors. The changes in the numbers and function of Tfh cells observed here, and by others during the course of SARS-CoV-2 infection, may justify the impaired development of an effective humoral response in this disease [ 9 , 10 , 13 , 15 ]. Still, it is important to emphasize that our study demonstrates that some changes in Tfh subsets persists at least until 6 months after the infection onset; and to conjecture about how those alterations challenge an effective immune response in these individuals and whether they are reverted upon vaccination.…”

“…No differences were found when comparing symptomatic and asymptomatic recovered individuals, either at T1 or T2, in what concerns to IgA Spike-specific antibodies serum levels, IgG Spike- and NP-specific antibodies serum levels, Spike- and NP-specific T cells (Table 1 ), or the percentage and absolute number of circulating CD4 + T follicular helper (Tfh) cells and their subpopulations. However, some studies reported an increase of IgG levels and of some Tfh cell subsets in severe COVID-19, when compared to non-severe disease [ 9 , 10 ], but the time since recovery is shorter than the one in our study and, as described by Zhao et al, the altered parameters tend to normalize with time [ 13 ].…”

“…Circulating SARS-CoV-2 Spike-specific Tfh cells are detected in infected patients [ 9 ]. Nevertheless, this T cell subset displays a decreased percentage of cells, and an altered phenotype and function in SARS-CoV-2 infected, convalescent, or recovered individuals [ 10 – 13 ]. COVID-19 patients also present an extreme reduction in the formation of germinal centers in thoracic lymph nodes, when compared to other types of pneumonia [ 14 , 15 ].…”

Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection

“…However, the frequencies of cTfh cells in both the LCR and SCR cohorts were lower than those in the healthy donor cohort (HD). Moreover, three cTfh subsets were similar between the LCR and HD cohorts; cTfh1 cell frequencies in the SCR cohort were shown to be significantly low, but cTfh2 and cTfh17 subsets were found to be high compared with the LCR and HD cohorts (158). Virus-specific Tfh cell frequencies, memory B cell responses, and serum CXCL13 levels were not different between asymptomatic or mild symptomatic COVID-19 patients.…”

The role of T‐cell immunity in COVID‐19 severity amongst people living with type II diabetes

“…This demonstrates that long-lived T cells can be established following infection with coronaviruses. Short-term longitudinal studies have thus far identified SARS-CoV-2-specific T cells up to 6-8 months postinfection [74][75][76]. Only time will tell how long-lasting SARS-CoV-2-specific T cells will be.…”