Priyanka Saminathan, Ph.D.

What if we could uncover the biological mechanism that makes men more vulnerable to COVID-19?

COVID-19 infection begins as a mild upper respiratory tract infection for most individuals and rapidly evolves into a severe respiratory distress syndrome, acute respiratory failure, coagulopathy, septic shock, and metabolic acidosis in a subset of patients. A recent metadata analysis of more than 3 million cases across the globe has shown that men are three times more likely to require intensive care therapy in comparison to their female counterparts. Several factors such as sex hormones and their ability to modulate an inflammatory response have been theorized as possible causes for this disparity. Increased interferon beta (IFNβ – an inflammatory cytokine) expression in females has been previously associated with antiviral effects with a more favorable clinical outcome during viral infection. In an attempt to unravel this mysterious phenomenon, our lab has been closely analyzing human metabolomic data from several COVID-19 patient cohorts. We observed that the ADA2 (adenosine deaminase 2) enzyme, which has been previously shown by the Sharma lab to inhibit the production of IFNβ, has higher enzyme activity in the serum of male patients in comparison with their female counterparts. We hypothesize that the increased ADA2 activity therefore suppresses the production of a robust and early antiviral response in men, and therefore contributes to the previously described sex bias among COVID patients. By modeling COVID-19 infections in a humanized COVID-mouse model, we will monitor disease onset, severity, viral dissemination, and lethality in the presence of increased ADA2 activity. Thus, through this current proposal we hope to validate the importance of ADA2 activity and the role it plays in the SARS-CoV-2 pathology.

SPARKing Impact: The study will provide new insight into sex-based differences in individuals’ susceptibility to severe COVID-19 with the potential to reveal new drug targets to treat the disease.