ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition.

COVID-19 severity has varied widely, with demographic and cardio-metabolic factors increasing risk of severe reactions to SARS-CoV-2 infection, but the underlying mechanisms for this remain uncertain. We investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 ( ), which has been shown to act as a receptor for SARS-CoV-2 cellular entry. In a meta-analysis of three independent studies including up to 1,471 participants, lower adipose tissue expression was associated with adverse cardio-metabolic health indices including type 2 diabetes (T2D) and obesity status, higher serum fasting insulin and BMI, and lower serum HDL levels (P<5.32x10 ). expression levels were also associated with estimated proportions of cell types in adipose tissue; lower expression was associated with a lower proportion of microvascular endothelial cells (P=4.25x10 ) and higher macrophage proportion (P=2.74x10 ), suggesting a link to inflammation. Despite an estimated heritability of 32%, we did not identify any proximal or distal genetic variants (eQTLs) associated with adipose tissue expression. Our results demonstrate that at-risk individuals have lower background levels in this highly relevant tissue. Further studies will be required to establish how this may contribute to increased COVID-19 severity.