Plasma ACE2 activity is persistently elevated following SARS-CoV-2 infection: implications for COVID-19 pathogenesis and consequences

Patel, Sheila K.; Juno, Jennifer A.; Lee, Wen Shi; Wragg, Kathleen M.; Hogarth, P. Mark; Kent, Stephen J.; Burrell, Louise M.

COVID-19 causes persistent endothelial inflammation, lung, cardiovascular, kidney and neurological complications as well as thromboembolic phenomena of unclear pathogenesis [1]. SARS-CoV-2 utilises the catalytic site of full-length membrane-bound angiotensin converting enzyme 2 (ACE2) for host cell entry [2], which is thought to downregulate membrane-bound ACE2, and thus contribute to ongoing inflammation due to loss of a degradative pathway for angiotensin II. In healthy individuals, ACE2 exists primarily in its membrane-bound form with very low levels of the catalytically active ectodomain of ACE2 present in the circulation [3]. However, in patients with cardiovascular disease, there is increased “shedding” of ACE2, and higher circulating levels are associated with downregulation of membrane-bound ACE2 [4].