Dysfunctional Coagulation in COVID-19: From Cell to Bedside

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which can induce multisystem disease. Human angiotensin-converting enzyme 2 (ACE2) widely expressing in arterial and venous endothelial cells and arterial smooth muscle cells has been identified as a functional receptor for SARS-CoV-2. Dysfunction of ACE2 leads to abnormal activation of the renin-angiotensin system and a systemic endotheliitis that may relate to abnormal coagulation and sepsis. Meanwhile, innate immune response and inflammation activation participate in dysfunctional coagulation. Previous research indicated that dysfunctional coagulation was one of the important risk factors accountable for a high risk of severe disease and death in patients with COVID-19. Understanding the possible mechanisms of dysfunctional coagulation and appropriate anticoagulation therapeutic strategies are important to prevent disease deterioration and reduce fatality rates during the ongoing COVID-19 pandemic.

Keywords: ACE2; COVID-19; Dysfunctional coagulation; SARS-CoV-2.

Fig. 1

Mechanisms of dysfunctional coagulation in COVID-19. Dysfunction of ACE2 leads to abnormal RAS activation, which promotes platelet adhesion and aggregation following the invasion of SARS-CoV-2. Meanwhile, inflammatory cytokines activate the coagulation cascade. COVID-19 coronavirus disease 2019, SARS-CoV-2 severe acute respiratory syndrome-coronavirus 2, ACE2 angiotensin-converting enzyme 2, Ang I angiotensin I, Ang II angiotensin II, Ang-(1-9) angiotensin-(1-9), Ang-(1-7) angiotensin-(1-7), AT1R angiotensin II type 1 receptor, RAS renin-angiotensin system, TNF-α tumor necrosis factor-α, IL-1β interleukin-1β, IL-6 interleukin-6, ACEI angiotensin-converting enzyme inhibitors, ARB angiotensin II receptor blocker

Fig. 2

Multiorgan injuries in COVID-19. COVID-19 coronavirus disease 2019, CNS central nervous system, AIS acute ischemic stroke, CVS cardiovascular system, ACS acute coronary syndrome, ALT alanine transaminase, AST aspartate transaminase, ARDS acute respiratory distress syndrome, AKI acute kidney injury