Figure 2.

Extrapulmonary manifestations of COVID-19 identified in severe and critically ill patients (percentage in hospitalized patients).

Extrapulmonary manifestations are observed in one quarter to one third of hospitalized patients. Four mechanisms are involved in the pathophysiology of multiorgan injury: i. the direct viral toxicity, ii. Dysregulation of the renin-angiotensin-aldosterone system (RAAS). iii. Endothelial cell damage and thrombo-inflammation and iv. Dysregulation of the immune system and cytokine release syndrome that causes disseminated organ injuries. Histopathological analyses identified the virus in the lung, the kidney, the myocardium, the brain, and the gastro-intestinal tissues.^12-18 The ACE2 and TMPRSS2 expression were confirmed by single cell RNA seq in epithelial cells of these organs.^16,19. The entry of SARS-CoV-2 via ACE2 receptor in endothelial cells of arterial and venous capillaries generates the recruitment of innate immunosuppressive cells with pro-thrombotic features (“viral sepsis” like syndrome), favoring micro- and macro- thromboembolic events (stroke, infarction, myocarditis and pericarditis).