Nauen DW, Hooper JE, Stewart CM, et al. - Despite evidence suggesting brain involvement in coronavirus disease 2019 (COVID-19), investigations in autopsies from patients with COVID-19 who had neurologic abnormalities (reviewed in the study by Mukerji and Solomon) did not suggest significant chronic inflammation or marked neural changes typically linked with viral infection, and viral genetic material. Hence it has been challenging to reconcile the experience of patients and clinicians that COVID-19 is affecting cognition with tissue studies that yield no evidence of encephalitis involving higher brain centers. Per researchers' hypothesis, histopathology might provide insight. In this work, brain tissue from autopsies of patients with nucleic acid–proven severe acute respiratory syndrome coronavirus 2 infection were evaluated by the researchers. Assessment of the brains from the first 5 such cases at Johns Hopkins University was done; for 2 of these, only fragments of the brain were available. Prior to this pandemic, megakaryocytes had not been detected in brain vessels by the study neuropathologists (D.W.N. and I.H.S.), and no reference to this was identified in the literature. These cells were described in an infarcted brain in COVID-19 in a recent report, indicating their possible presence in the brain circulation and entry into the parenchyma during hemorrhage. As per multiple lines of evidence, endothelial dysfunction may contribute to severe COVID-19 illness. Megakaryocytes had been detected in lung examination, and now there are reports describing the presence of these cells in other organs. 33% of examined cases showed megakaryocytes in cortical capillaries. Because the standard brain autopsy sections taken sampled at random only a minute portion of the cortical volume, finding these cells suggests the total burden could be considerable. These large cells, possibly by creating occlusion of the flow through individual capillaries, cause ischemic alteration in a different pattern, potentially leading to an atypical form of neurologic impairment.