IL-18-dependent MAIT cell activation in COVID-19

Flament et al. report a marked reduction of circulating mucosal-associated invariant T (MAIT) cells in patients with severe COVID-19, compared with controls sharing co-morbidities. These MAIT cells had very high levels of activation that correlated with disease severity. Among T cells, alterations in MAIT cells preferentially associated with mortality, and high CD69 expression correlated with poor outcome. Severe inflammation, particularly high levels of IL-18, was associated with increased cytotoxicity of circulating MAIT cells. Co-culture studies of in vitro SARS-CoV-2-infected macrophages with MAIT cells suggest a two-step process of MAIT cell activation, through type I IFN and later IL-18. Together with other reports, this preprint supports a pivotal role for MAIT cells, through an IL-18-dependent mechanism, in the pathology of COVID-19.