PMC:7402624 / 18561-21565 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7402624","sourcedb":"PMC","sourceid":"7402624","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7402624","text":"We next examined six well-defined CD4 T cell subsets as above for the CD8 T cells, including naïve, effector memory (EM1,2,3), central memory (CM), and EMRA (Fig. 3A). Given the potential role of antibodies in the response to SARS-CoV2 (27, 29), we also analyzed circulating Tfh (CD45RA−PD1+CXCR5+ [cTfh] (36)) and activated circulating Tfh (CD38+ICOS+ [activated cTfh]), the latter of which may be more reflective of recent antigen encounter and emigration from the germinal center (37, 38) (Fig. 3A). These analyses revealed a relative loss of naïve CD4 T cells compared to controls, but increased EM2 and EMRA (Fig. 3B). The frequency of activated but not total cTfh was statistically increased in COVID-19 patients compared to HD, though this effect appeared to be driven by a subgroup of patients (Fig. 3B). It is worth noting that activated cTfh frequencies were also higher in RD compared to HD (Fig. 3B), perhaps reflecting residual COVID-19 responses in that group. Frequencies of KI67+ or CD38+HLA-DR+ non-naïve CD4 T cells were increased in COVID-19 patients (Fig. 3, C and E); however, this change was not equivalent across all CD4 T cell subsets. The most substantial increases in both KI67+ and CD38+HLA-DR+ cells were found in the effector memory populations (EM, EM2, EM3) and in cTfh (fig. S3, A and B). Although some subjects had increased activation of EMRA, this was less pronounced. In contrast, PD1 expression was increased in all other non-naïve populations compared to HD or RD (fig. S3C). Co-expression of CD38 and HLA-DR by non-naïve CD4 T cells correlated with the frequency of KI67+ non-naïve CD4 T cells (fig. S3D). Moreover, the frequency of total non-naïve CD4 T cells that were CD38+HLA-DR+ correlated with the frequency of activated cTfh (fig. S3E). In general, the activation of CD4 T cells was correlated with the activation of CD8 T cells (Fig. 3, D and F). However, whereas ~2/3 of patients had KI67+ non-naïve CD4 or CD8 T cell frequencies above controls, ~1/3 of the COVID-19 patients had no increase in frequency of KI67+ CD4 or CD8 T cells above that observed in HD (Fig. 3, D and F). Moreover, although most patients had similar proportions of activated CD4 T cells compared to CD8 T cells, there was a subgroup of patients that had disproportionate activation of CD4 T cells compared to CD8 T cells (Fig. 3, D and F). KI67+ and CD38+HLA-DR+ non-naïve CD4 T cell frequencies correlated with ferritin and with APACHE III score (fig. S3F), suggesting a relationship between CD4 T cell activation and disease severity. Immunosuppression did not impact CD4 T cell activation; however, early steroid administration was weakly associated with CD4 T cell KI67 (fig. S3F). Together, these data highlight T cell activation in COVID-19 patients similar to what has been observed in other acute infections or vaccinations (37, 39, 40), but also identify patients with high, low, or essentially no T cell response based on KI67+ or CD38+HLA-DR+ compared to control 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