Molecular mechanisms of vasculopathy and coagulopathy in COVID-19

Abstract

Abstract COVID-19 primarily affects the respiratory system and may lead to severe systemic complications, such as acute respiratory distress syndrome (ARDS), multiple organ failure, cytokine storm, and thromboembolic events. Depending on the immune status of the affected individual early disease control can be reached by a robust type-I-interferon (type-I-IFN) response restricting viral replication. If type-I-IFN upregulation is impaired, patients develop severe COVID-19 that involves profound alveolitis, endothelitis, complement activation, recruitment of immune cells, as well as immunothrombosis. In patients with proper initial disease control there can be a second flare of type-I-IFN release leading to post-COVID manifestation such as chilblain-like lesions that are characterized by thrombosis of small vessels in addition to an inflammatory infiltrate resembling lupus erythematosus (LE). Mechanistically, SARS-CoV-2 invades pneumocytes and endothelial cells by acting on angiotensin-II-converting enzyme 2 (ACE2). It is hypothesized, that viral uptake might downregulate ACE2 bioavailability and enhance angiotensin-II-derived pro-inflammatory and pro-thrombotic state. Since ACE2 is encoded on the X chromosome these conditions might also be influenced by gender-specific regulation. Taken together, SARS-CoV-2 infection affects the vascular compartment leading to variable thrombogenic or inflammatory response depending on the individual immune response status.