Functional alteration of innate T cells in critically ill Covid-19 patients

Jouan, Y.; Guillon, A.; Gonzalez, L.; Perez, Y.; Ehrmann, S.; Ferreira, M.; Daix, T.; Jeannet, R.; Francois, B.; Dequin, P.-F.; Si-Tahar, M.; Baranek, T.; Paget, C.

Covid-19 can induce lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors in Covid-19-driven ARDS are poorly understood. Here, we dynamically analyzed the biology of innate T cells, a heterogeneous class (MAIT, {gamma}{delta}T and iNKT cells) of T lymphocytes, presenting potent anti-infective and regulatory functions. Patients presented a compartmentalized lung inflammation paralleled with a limited systemic inflammation. Circulating innate T cells of critically ill Covid-19 patients presented a profound and persistent phenotypic and functional alteration. Highly activated innate T cells were detected in airways of patients suggesting a recruitment to the inflamed site and a potential contribution in the regulation of the local inflammation. Finally, the expression of the CD69 activation marker on blood iNKT and MAIT cells at inclusion was predictive of disease severity. Thus, patients present an altered innate T cell biology that may account for the dysregulated immune response observed in Covid-19-related acute respiratory distress syndrome.