SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. In this article the authors present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. The authors demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. They further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, a pathophysiological state in swine induced by RAAS imbalance was shown sharing several features with the clinical COVID-19 presentation. Therefore, the authors propose that severe COVID-19 could partially be driven by a RAAS imbalance.
Rysz S, Al-Saadi J, Sjöström A, Farm M, Campoccia Jalde F, Plattén M, Eriksson H, Klein M, Vargas-Paris R, Nyrén S, Abdula G, Ouellette R, Granberg T, Jonsson Fagerlund M, Lundberg J. COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system. Nat Commun. 2021 Apr 23;12(1):2417. doi: 10.1038/s41467-021-22713-z