Coagulation dysfunction in COVID-19: The interplay between inflammation, viral infection and the coagulation system

Abstract

COVID-19 is a new pandemic, caused by Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-Cov2) infection and characterized by a broad spectrum of clinical manifestations. Inflammation and the innate immune system have been recently recognized as pivotal players in the most severe forms, characterized by significantly elevated levels of pro-inflammatory cytokines. In this setting, several studies have also reported the presence of abnormalities in coagulation parameters and platelets count, possibly identifying a subgroup of patients with poor prognosis. Some reports of full-blown thromboembolic events are emerging. Among the possible mechanisms underlying coagulation dysfunction, the so-called "cytokine storm" seems to play a pivotal role. Other candidate factors include virus-specific mechanisms, related to the virus interaction with renin angiotensin system (RAS) and the fibrinolytic pathway, but also comorbidities affecting these patients. Coagulation dysfunction is therefore a candidate risk factor for adverse outcomes in COVID-19 and should be carefully addressed in clinical practice.

Keywords: COVID-19; Coagulation; Inflammation; SARS-CoV2; Thrombosis.

Fig. 1

Simplified scheme of the potential virus-specific effects in the imbalance between coagulation and fibrinolysis. a. Physiologically, ACE2 counterbalances the effects of renin-angiotensin system by degrading Ang II, with no effects on the balance between coagulation and fibrinolysis. b. During SARS-CoV-2 infection, the availability of ACE2 decreases because scavenged by the virus, enhancing Ang II availability. This favours the activation of a systemic procoagulant environment, together with the virus-mediated enhancement of PAI-1 production. ACE2: Angiotensin Converting Enzyme II; Ang II: Angiotensin II; PAI-1: Plasminogen Activator Inhibitor-1. Created with BioRender (academic license).