Covid-19, induced activation of hemostasis, and immune reactions: Can an auto-immune reaction contribute to the delayed severe complications observed in some patients?

Abstract

Covid-19 is characterized by weak symptoms in most affected patients whilst severe clinical complications, with frequent fatal issues, occur in others. Disease severity is associated with age and comorbidities. Understanding of viral infectious mechanisms, and antibody immune response, can help to better control disease progression. SARS-CoV-2 has a major impact on the Renin Angiotensin Aldosterone System (RAAS), through its binding to the membrane cellular glycoprotein, Angiotensin Converting Enzyme-2 (ACE-2), then infecting cells for replication. This report hypothesizes the possible implication of an autoimmune response, induced by generation of allo- or autoantibodies to ACE-2, or to its complexes with viral spike protein. This could contribute to some delayed severe complications occurring in affected patients. We also propose a strategy for investigating this eventuality.

Keywords: ACE-2; Angiotensin II; Autoantibodies; Covid-19; Disease severity; Hemostasis; Spike protein S.

Fig. 1

ACE-2 regulates blood pressure and volume, inflammation, diuresis, N+/K + balance, and protects organs (mainly lung, heart and liver) from fibrosis. It is a key cell transmembrane glycoprotein which prevents hypertension and protects from tissue injury by opposing the activation of the Renin Angiotensin Aldosterone System (RAAS), and the deleterious effects of Angiotensin II (AII) and Aldosterone. Through its binding to ACE2, SARS-CoV-2 infects cells, such as lung alveolar epithelial cells (where ACE-2 is highly expressed), and interferes in the RAAS, by impacting ACE-2 beneficial action. We hypothesize that binding of SARS-CoV-2 S Protein to ACE-2 could induce generation of allo- or/and autoantibodies.