Figure 1.

Representation of the cardiovascular derangements of coronavirus disease 2019 (COVID-19) that are due to either direct cellular damage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or indirect consequences of the exaggerated host’s response. The severe acute respiratory syndrome coronavirus of 2019 (SARS-CoV-2) is a single-strand positive-sense RNA virus that spreads between humans mainly through the inhalation of respiratory droplets. Upon the collapse of the alveoli in the lungs, the virus can enter the bloodstream and distribute to systemic districts by cardiac pumping. It is likely that the transport in the blood is not as such, but carried by different types of white blood cells, such as T cells, granulocytes, and macrophages, which can therefore serve as vehicles. This Trojan route can guarantee the infiltration of the virus into normally inaccessible body districts. The systemic spread of the coronavirus elicits an exaggerated immune response in the most severe cases that strokes with hypoxic conditions. (A) In the myocardium, the excessive activation of the endothelial system upon viral damage and the enhanced inflammatory cell infiltration alter the coronary perfusion and the cardiac rhythm. Circulating monocytes and neutrophils infiltrate in the heart wall and parenchyma, with resident dendritic cells contributing to cytokine production and inflammatory/pro-fibrotic environment. (B) In the blood, the hyperactivation of both inflammatory and microthrombotic pathways leads to endothelium engrossment and coagulopathy. The activated vascular endothelium is targeted by neutrophils and monocytes, with thrombosis or bleedings being likely to occur because of the inflammation-derived imbalance between platelets, hypercoagulability, and altered fibrinolysis (fibrin in green). Thrombus-associated white blood cells produce inflammatory cytokines and proteases that contribute to local remodeling and fibroblast activation. Atherothombotic manifestations may also be promoted by dysregulation of neutrophil extracellular traps (NETs). (C) The heart is innervated by vagal postganglionic fibers from the cardio-inhibitory center and by the cardiac postganglionic fibers from the spinal cord arising from the cardio-acceleratory center of the medulla. Sympatho-inhibitory and cardio-inhibitory baroreflexes together with arterial metaboreflexes encompass inputs to neurons located in the dorsolateral nucleus of the solitary tract that integrate the vasomotor tone and the automatism of the sinus node. Damages to these reflexes disturb these central pathways and ultimately disrupt the heart beat nuclei, eventually leading to irrepressible dysautonomia.