Brain pathology of COVID-19

Introduction: SARS-COV2 may cause a wide range of neurological manifestations in about 30% of covid 19 patients. Cases of encephalitis have been described in patients presented with severe respiratory distress with estimated incidence of 58/100,000 patients. However, the correlated pathological changes of these cases of encephalitis and its pathogenesis are poorly understood. Methods: We have examined brains from 23 randomly referred cases of patients dying with COVID-19, with spectrum of neuropathological findings such as hypoxic-ischemic changes, infarcts, hemorrhages and necrotizing encephalopathy and mild to moderate increase in number of activated microglia cells. There are 5 cases of intense infiltration of brainstem structures with microglia cells and mild T lymphocyte infiltration which raises the possibility of what is called "brainstem encephalitis" although with poorly correlated neurological manifestations. In these cases, there is intense activation of microglia cells with microglia nodules formation and mild infiltration with T lymphocytes but there is no significant demyelination, necrosis or axonal damage. The immunohistochemistry and in-situ hybridization failed to demonstrate SARS-COV2 virus or other viruses. On the other hand, we found only mild increase in number of activated microglia cells but without microglial nodules in the brainstem of 3/6 patients that died from non-COVID related septicemia and multi-organ failure. Results: These results suggest that the inflammatory changes in the brainstem structures are most likely related to peculiar substantial systemic inflammatory reaction and massive release of cytokines (cytokines storm) in COVID-19 patient causing activation of innate immunity and alteration of blood brain barrier (BBB) in brainstem structures. Therefore, this pathology should be termed as "COVID- 19 encephalopathy" rather than encephalitis. Conclusion: This and other works highlighted the importance for more research into the role of microglia cells in brain pathology in acute and long Covid19 diseases including psychiatric manifestations.