Plasma levels of soluble ACE2 are associated with sex, Metabolic Syndrome, and its biomarkers in a large cohort, pointing to a possible mechanism for increased severity in COVID-19

We examined the associations between plasma concentrations of soluble ACE2 and biomarkers of Metabolic Syndrome in a large (N=2,051) sample of individuals who participated in a commercial wellness program and who underwent deep molecular phenotyping. sACE2 levels were significantly higher in men, compared to women, and in individuals with Metabolic Syndrome, compared to controls. sACE2 levels showed reliable associations with all individuals components of Metabolic Syndrome, including obesity, hypertension, insulin resistance, hyperlipidemia, and as well as markers of liver damage. This profile of associations was statistically significantly stronger in men, compared to women, and points to preexisting cardiometabolic conditions as possible risk factors for increased severity of symptoms in some COVID-19 patients through increased expression of ACE2 in the liver.