High adenosine deaminase 2 activity in males associates with poor SARS-CoV-2 immunity

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Presentation Time: 08:45 AM - 09:00 AM
Abstract ID: 5443 - B

Presenting Author:
Priyanka Saminathan , Posdoctoral Fellow at La Jolla Inst. for Immunol.

Abstract:

Introduction: Male sex has been identified as a risk factor for severe COVID-19-related ICU admissions and death. Anti-viral innate immunity is influenced by biological factors including age and sex. The female sex is associated with more robust type-1 interferon production aiding in a more efficient anti-viral response. We’ve identified the isoenzyme Adenosine Deaminase 2 (ADA2) as an inhibitor of IFNβ production and the resulting IFNβ-driven anti-viral gene expression response (ISG). The mechanism involves inhibiting the expression of immune-stimulatory endogenous retroviral elements (ERV), innate immune ligands that stimulate low levels of IFNβ. Here we examined sex-bias in expression and activity of ADA2, and its influence on clinical outcomes of COVID-19. Methods: Using multiple patient cohorts (COVID infectivity +/-), ADA2 activity was assessed using high-resolution liquid chromatography-tandem mass spectrometry. Publicly available databases and resources were employed to further examine the relationship between ADA2 and IFNβ/IFNβ-driven gene expression. Results: Extracellular ADA2 activity was significantly higher in males. Monocytes from acutely SARS-CoV-2 infected lungs showed a strong male-bias in ADA2 expression. Females exhibited comparatively higher ERV expression in lung at baseline, and robust expression of ERV and ISG during COVID infectivity. Conclusion: High ADA2 activity contributes to the male sex being a risk factor for severe COVID-19 disease.