LAUSR

In this article in EBioMedicine, Zsuzsanna Varga and colleagues [1] published an immunohistochemistry-based study for the presence of ACE2 receptor, T-cell markers, and macrophage markers, in different anatomical regions of the coronary tree of six COVID-19 patients who died of respiratory or multiorgan failure. They found that the small heart vessels, capillaries, arterioles/venules were affected by inflammatory injury and exhibited a high density of endothelial ACE2 expression whereas the major coronary arteries were weakly or not at all affected. Interestingly, they found high ACE2 expression and an inflammatory neuropathy of the epicardial nerves, which could help to clarify the prevalence of cardiac comorbidities such as myocardial injury and arrhythmias in COVID-19. I wish to underscore a few key points. From the first pathological studies, vascular damage and the presence of disseminated thrombotic small vessel microangiopathy appeared as typical hallmarks of severe SARS-CoV-2 infection, not only in the lung but also in the systemic circulation and several other organs distal to the lung (for a review, see [2]). Both autoimmunity and neurotropism appear to be involved in COVID-19 neuropathies [3]. The immune-mediated injury mechanism of the myelin sheath is known as "molecular mimicry” [4]. The surface glycoproteins of the virus, against which antibodies are produced during infection, resemble neuronal glycoconjugates. For this reason, the neurons are targeted by the same antibodies, causing their injury [3]. The high expression of ACE2 in epicardial nerves found in this study, suggests the possibility of a neurotropic mechanism of SARS-CoV-2 injury. However, further studies are needed to verify the colocalization of viral RNA or spike protein with both ACE2 receptor and inflammatory markers, to unequivocally give a response to the relevant question of the direct cardiac injury. The authors describe a major density of ACE2 receptor in capillaries and in small arterioles and venules, supporting the