Entry of SARS-COV-2 into mammalian cells is mediated by angiotensin-converting enzyme 2 (ACE2). This binding and consequent ACE2 endocytosis have potential to disrupt blood pressure regulation by interfering with ACE2-mediated cleavage of angiotensin II (AngII). Now, Swartz and colleagues suggest that SARS-CoV-2 infection might also dysregulate vascular tension in patients with severe COVID-19 by promoting the formation of anti-AngII autoantibodies.

Credit: Springer Nature Limited

The researchers detected anti-ACE2 antibodies in serum from hospitalized patients with COVID-19, and the antibody levels correlated strongly with blood pressure dysregulation and disease severity (based on blood oxygenation levels). Mouse monoclonal anti-AngII antibodies cross-reacted with recombinant SARS-CoV-2 spike protein, indicating that epitope mimicry might contribute to the generation of autoantibodies in infected individuals. In vitro, monoclonal anti-ACE2 antibodies interfered with binding of AngII to AngII receptor type 1, suggesting antagonism of AngII function.