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bioRxiv · 10.1101/2020.12.01.407007

Multimodal Single-Cell Omics Analysis of COVID-19 Sex Differences in Human Immune Systems

Hou, Y.·Zhou, Y.·Gack, M.·Lathia, J.·Kallianpur, A.·Mehra, R.·Chan, T.·Jung, J. U.·Jehi, L.·Eng, C.·Cheng, F.
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Abstract

Sex differences in the risk of SARS-CoV-2 infection have been controversial and the underlying mechanisms of COVID-19 sexual dimorphism remain understudied. Here we inspected sex differences in SARS-CoV-2 positivity, hospitalization, admission to the intensive care unit (ICU), sera immune profiling, and two single-cell RNA-sequencing (snRNA-seq) profiles from nasal tissues and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with varying degrees of disease severity. Our propensity score-matching observations revealed that male individuals have a 29% increased likelihood of SARS-CoV-2 positivity, with a hazard ration (HR) 1.32 (95% confidence interval [CI] 1.18-1.48) for hospitalization and HR 1.51 (95% CI 1.24-1.84) for admission to ICU. Sera from male patients at hospital admission had decreased lymphocyte count and elevated inflammatory markers (C-reactive protein, procalcitonin, and neutrophils). We found that SARS-CoV-2 entry factors, including ACE2, TMPRSS2, FURIN and NRP1, have elevated expression in nasal squamous cells from males with moderate and severe COVID-19. Cell-cell network proximity analysis suggests possible epithelium-immune cell interactions and immune vulnerability underlying a higher mortality in males with COVID-19. Monocyte-elevated expression of Toll like receptor 7 (TLR7) and Bruton tyrosine kinase (BTK) is associated with severe outcomes in males with COVID-19. These findings provide basis for understanding immune responses underlying sex differences, and designing sex-specific targeted treatments and patient care for COVID-19.

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Hou, Y., Zhou, Y., Gack, M., Lathia, J., Kallianpur, A., Mehra, R., Chan, T., Jung, J. U., Jehi, L., Eng, C., Cheng, F.. 2020-12-01. Multimodal Single-Cell Omics Analysis of COVID-19 Sex Differences in Human Immune Systems. https://doi.org/10.1101/2020.12.01.407007

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