PMC:7402624 / 36943-39187
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7402624","sourcedb":"PMC","sourceid":"7402624","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7402624","text":"However, in all cases, these temporal patterns were complex, with frequencies of subpopulations in individual patients appearing to increase, decrease, or stay the same over time. To quantify these inter-patient changes, we used a previously described data set (46) to define the stability of populations of interest in healthy individuals over time. We then used the range of this variation over time to identify COVID-19 patients with changes in immune cell subpopulations beyond that expected in healthy subjects (see methods). Using this approach, ~50% of patients had an increase in HLA-DR+CD38+ non-naïve CD4 T cells over time, whereas in ~30% of patients, these cells were stable and, in ~20%, they decreased (Fig. 5E). For KI67+ non-naïve CD8 T cells, there were no individuals in whom the response decreased. Instead, this proliferative CD8 T cell response stayed stable (~70%) or increased (~30%; fig. S6A). Notably, for patients in the stable category, the median frequency of KI67+ non-naïve CD8 T cells was ~10%, almost 5-fold higher than the ~1% detected for HD and RD subjects (Figs. 5C and 2E), suggesting a sustained CD8 T cell proliferative response to infection. A similar pattern was observed for HLA-DR+CD38+ non-naïve CD8 (fig. S6B), where only ~10% of patients had a decrease in this population, whereas ~65% were stable and ~25% increased over time. The high and even increasing activated or proliferating CD8 and CD4 T cell responses over ~1 week during acute viral infection contrasted with the sharp peak of KI67 in CD8 and CD4 T cells during acute viral infections, including smallpox vaccination with live vaccinia virus (47), live attenuated yellow fever vaccine YFV-17D (48), acute influenza virus infection (49), and acute HIV infection (35). Approximately 42% of patients had sustained PB responses, at high levels (\u003e10% of B cells) in many cases (Fig. 5F). Thus, some patients displayed dynamic changes in T cell or B cell activation over 1 week in the hospital, but there were also other patients who remained stable. In the latter case, some patients remained stable without clear activation of key immune populations whereas others had stable T and or B cell activation or numerical perturbation (fig. 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