Journal
CELL
Volume 183, Issue 5, Pages 1340-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.10.001
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Funding
- NIH [U19AI14274, U19AI142742-0S1, U19AI118626, R01HL114093, R35-GM128938, S10RR027366, S10OD025052]
- William K. Bowes, Jr. Foundation
- Whittaker Foundation
- Wessex Clinical Research Network
- National Institute for Health Research UK
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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.
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