Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe coronavirus disease 2019 (COVID-19) in a small proportion of infected individuals. The immune system plays an important role in the defence against SARS-CoV-2, but our understanding of the cellular immune parameters that contribute to severe COVID-19 disease is incomplete. Here, we show that populations of human effector γδ T cells are associated with acute COVID-19 in unvaccinated patients. We found that circulating killer-type γδ T cells were enriched in COVID-19 patients with acute disease. Surprisingly, SARS-CoV-2 infection did not alter the γδ T cell receptor repertoire, like in other viral infections. Thus, our work demonstrates a link between the systemic activation of effector populations of γδ T cells and acute COVID-19 in unvaccinated individuals.

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