Id |
Subject |
Object |
Predicate |
Lexical cue |
T117 |
0-167 |
Sentence |
denotes |
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). |
T118 |
168-502 |
Sentence |
denotes |
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). |
T119 |
503-623 |
Sentence |
denotes |
These analyses revealed a relative loss of naïve CD4 T cells compared to controls, but increased EM2 and EMRA (Fig. 3B). |
T120 |
624-812 |
Sentence |
denotes |
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). |
T121 |
813-974 |
Sentence |
denotes |
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. |
T122 |
975-1159 |
Sentence |
denotes |
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. |
T123 |
1160-1320 |
Sentence |
denotes |
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). |
T124 |
1321-1403 |
Sentence |
denotes |
Although some subjects had increased activation of EMRA, this was less pronounced. |
T125 |
1404-1513 |
Sentence |
denotes |
In contrast, PD1 expression was increased in all other non-naïve populations compared to HD or RD (fig. S3C). |
T126 |
1514-1644 |
Sentence |
denotes |
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). |
T127 |
1645-1782 |
Sentence |
denotes |
Moreover, the frequency of total non-naïve CD4 T cells that were CD38+HLA-DR+ correlated with the frequency of activated cTfh (fig. S3E). |
T128 |
1783-1893 |
Sentence |
denotes |
In general, the activation of CD4 T cells was correlated with the activation of CD8 T cells (Fig. 3, D and F). |
T129 |
1894-2125 |
Sentence |
denotes |
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). |
T130 |
2126-2360 |
Sentence |
denotes |
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). |
T131 |
2361-2557 |
Sentence |
denotes |
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. |
T132 |
2558-2706 |
Sentence |
denotes |
Immunosuppression did not impact CD4 T cell activation; however, early steroid administration was weakly associated with CD4 T cell KI67 (fig. S3F). |
T133 |
2707-3004 |
Sentence |
denotes |
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 subjects. |