Summary

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.

Overall design

We collected 48 PBMC samples from 24 participants in this study. In exposed and infected cohorts, 13 subjects were sampled longitudinally with 2 or 3 samples per individual. Each sample is associated with 3 files of processed data and 12 files of raw data.

Contributors

Chen Yu†, Sejiro Littleton†, Xiling Shen✉️, Daniel R. Saban✉️

Contact

xiling.shen@duke.edu (Xiling Shen), daniel.saban@duke.edu (Daniel R. Saban)