Circulating effector gamma delta T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals

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 defense 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 effector gamma delta T cells are associated with COVID-19 in unvaccinated patients with acute disease. We found that circulating CD27(neg)CD45RA(+)CX3CR1(+) V delta 1(effector) cells expressing Granzymes (Gzms) were enriched in COVID-19 patients with acute disease. Moreover, higher frequencies of GzmB(+) V delta 2(+) T cells were observed in acute COVID-19 patients. SARS-CoV-2 infection did not alter the gamma delta T cell receptor repertoire of either V delta 1(+) or V delta 2(+) subsets. Our work demonstrates an association between effector populations of gamma delta T cells and acute COVID-19 in unvaccinated individuals.