ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19

Bruna GG Pinto; Antonio ER Oliveira; Youvika Singh; Leandro Jimenez; Andre NA Goncalves; Rodrigo LT Ogava; Rachel Creighton; Jean PS Peron; Helder I Nakaya

The molecular mechanism responsible for the increased disease severity in patients with these comorbidities is not fully understood, but previous studies suggest a role for angiotensin-converting enzyme 2 (ACE2) [5] . ACE2 is a membrane protein required for SARS-CoV2 to bind and enter cells [6] [7] [8] . After binding, viral entry is facilitated by the activation of the viral spike glycoprotein and cleavage of the C-terminal segment of ACE2 by proteases like TMPRSS2 and FURIN that are readily expressed in lung tissue [9] [10] [11] . ACE2 is only moderately expressed in healthy lung tissue compared to the heart, kidneys, and testes [12] , but staining of lung tissue sections from adults with pulmonary hypertension has revealed increased ACE2 protein in the endothelium of pulmonary arteries, compared to healthy controls [13] . ACE2 upregulation has also been observed in animal models of liver fibrosis [14] . However, the reason for this upregulation remains unclear, and a link to other COVID-19 comorbidities has not been determined.