Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19

Yu, Chen; Littleton, Sejiro; Giroux, Nicholas S.; Mathew, Rose; Ding, Shengli; Kalnitsky, Joan; Yang, Yuchen; Petzold, Elizabeth; Chung, Hong A.; Rivera, Grecia O.; Rotstein, Tomer; Xi, Rui; Ko, Emily R.; Tsalik, Ephraim L.; Sempowski, Gregory D.; Denny, Thomas N.; Burke, Thomas W.; McClain, Micah T.; Woods, Christopher W.; Shen, Xiling; Saban, Daniel R.

Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, yet the mechanisms governing this disparity remain incompletely understood. We carried out sex-balanced sampling of peripheral blood mononuclear cells from confirmed COVID-19 inpatients and outpatients, uninfected close contacts, and healthy controls for 36-color flow cytometry and single cell RNA-sequencing. Our results revealed a pronounced reduction of circulating mucosal associated invariant T (MAIT) cells in infected females. Integration of published COVID-19 airway tissue datasets implicate that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, female MAIT cells possessed an immunologically active gene signature, whereas male counterparts were pro-apoptotic. Collectively, our findings uncover a female-specific protective MAIT profile, potentially shedding light on reduced COVID-19 susceptibility in females.