The contribution of CD4 + T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown.

In this paper it’s presented 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, were found increased proportions of cytotoxic follicular helper (T FH ) cells and cytotoxic T helper 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 helper (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, these analyses provide insights into the gene expression patterns of SARS-CoV-2-reactive CD4 + T cells in distinct disease severities.