Mucosal-associated invariant T cell responses differ by sex in COVID-19

Background: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood. Methods: We carried out sex-balanced sampling of peripheral blood mononuclear cells from hospitalized and non-hospitalized individuals with confirmed COVID-19, uninfected close contacts, and healthy control individuals for 36-color flow cytometry and single-cell RNA sequencing. Findings: 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 suggests that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, MAIT cells from females possessed an immunologically active gene signature, whereas cells from males were pro-apoptotic. Conclusions: Our findings uncover a female-specific protective MAIT cell profile, potentially shedding light on reduced COVID-19 susceptibility in females.

Automated summary

The study revealed a significant reduction of circulating mucosal-associated invariant T (MAIT) cells in infected females, suggesting a major wave of MAIT cell extravasation in females during early infection. Additionally, MAIT cells from females displayed an immunologically active gene signature, while cells from males were more pro-apoptotic. These findings uncover a female-specific protective MAIT cell profile, potentially explaining reduced COVID-19 susceptibility in females.