Immunoinflammatory, Thrombohaemostatic, and Cardiovascular Mechanisms in COVID-19

Abstract

The global coronavirus disease 2019 (COVID-19) pandemic has deranged the recent history of humankind, afflicting more than 27 million individuals to date. While the majority of COVID-19 patients recuperate, a considerable number of patients develop severe complications. Bilateral pneumonia constitutes the hallmark of severe COVID-19 disease but an involvement of other organ systems, namely the cardiovascular system, kidneys, liver, and central nervous system, occurs in at least half of the fatal COVID-19 cases. Besides respiratory failure requiring ventilation, patients with severe COVID-19 often display manifestations of systemic inflammation and thrombosis as well as diffuse microvascular injury observed postmortem. In this review, we survey the mechanisms that may explain how viral entry and activation of endothelial cells by severe acute respiratory syndrome coronavirus 2 can give rise to a series of events including systemic inflammation, thrombosis, and microvascular dysfunction. This pathophysiological scenario may be particularly harmful in patients with overt cardiovascular disease and may drive the fatal aspects of COVID-19. We further shed light on the role of the renin-angiotensin aldosterone system and its inhibitors in the context of COVID-19 and discuss the potential impact of antiviral and anti-inflammatory treatment options. Acknowledging the comorbidities and potential organ injuries throughout the course of severe COVID-19 is crucial in the clinical management of patients affecting treatment approaches and recovery rate.

Fig. 1

Summary of systemic effects of SARS-CoV-2 infection on endothelial cells, immune cells, coagulation system, and cardiac inflammation. Viral infection first mediates endothelial dysfunction with observed changes in the RAAS system as well as inflammation, oxidative stress, upregulation of adhesion molecules for leukocyte recruitment, and intravascular coagulation leading toward microthrombi in the lungs. Inflammatory cytokine storms involving expression of macrophage IL-6 and TNF-α leading to hyperactivation and increased apoptosis of lymphocytes characterize systemic inflammation in severe COVID-19 patients. Ultimately, inflammation may be tied to both elevated levels of thrombosis and cardiac injury as observed in markers such as the D-dimer and troponin. Created with Biorender. CK, creatine kinase; IL-6, interleukin-6; NT-proBNP, NT-proB-type natriuretic peptide; RAAS, renin–angiotensin aldosterone system; TNF-α: tumor necrosis factor α.