Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4 + T Cells in COVID-19.

The contribution of CD4 ⁺ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present single-cell transcriptomic analysis of >100,000 viral antigen-reactive CD4 ⁺ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper cells and cytotoxic T helper (T _H ) cells (CD4-CTLs) responding to SARS-CoV-2 and reduced proportion of SARS-CoV-2-reactive regulatory T cells (T _REG ). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic T _FH response was observed early in the illness, which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional T _H 1 and T _H 17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4 ⁺ T cells compared to influenza-reactive CD4 ⁺ T cells. Together, our analyses provide insights into the gene expression patterns of SARS-CoV-2-reactive CD4 ⁺ T cells in distinct disease severities.
Competing Interests: Declaration of Interests The authors declare no competing interests.
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