Use of mait cells as biomarkers and biotargets in covid-19

Immune system dysfunction is paramount in Coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, the inventors studied the immune cell landscape, with emphasis on MAIT cells, in a cohort of 182 patients including patients at various stages of disease activity. A profound decrease of MAIT cell counts in blood of critically ill patients was observed. These cells showed a strongly activated and cytotoxic phenotype that positively correlated with circulating pro-inflammatory cytokines, notably IL-18. MAIT cell alterations markedly correlated with disease severity and patient mortality. In vitro, SARS-CoV-2-infected macrophages activated “naïve” MAIT cells in a cytokine-dependent manner involving an IFNa-dependent early phase and an IL-18-induced later phase. The inventors propose altered MAIT cell phenotype as a hallmark of disease severity and provide a rationale for adapted anti-inflammatory therapy targeting IL-18 or its receptor in most severe patients.

Keywords: COVID19, Severe form prognosis, MAIT cells
Patent Application number: EP 20 305 961.3 on 28/08/2020

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