[Diffuse changes in the brain in the acute phase of COVID-19 and after infection].

Abstract

There is no consolidated opinion on the pathogenesis of neurological manifestations of COVID-19, especially after infection. A significant contribution to understanding the mechanisms of neuropathology in COVID-19 can be made by detailed morphologic studies of the brain with assessment of changes in different brain regions during different periods of the infection process.

Objective: Clarification of the nature of brain morphologic changes and intracerebral virus invasion in COVID-19 and postinfection.

Material and methods: The study included 15 patients who died during the acute phase of COVID-19 (11 people) or after an infection (4 people) without a history of acute focal changes in the brain or neurological diseases. In each case, 9 brain areas were assessed, including the cortex, hippocampus, brainstem (pons and medulla oblongata), cerebellum, basal ganglia, and central parts of the olfactory system. In addition to the histological study, an immunohistochemical study was performed using antibodies against CD8, Iba1, as well as SARS-CoV-2 proteins (S1 and N) and a semi-quantitative assessment of circulatory disorders, microglial reaction and expression of the SARS-CoV-2 S1 protein in the brain.

Results: The neuropathological picture was similar in the acute and post-infectious phases of COVID-19: microcirculatory disorders, diffuse cerebral edema, ischemic-hypoxic neuronal changes, accumulations of corpora amylacea, gliosis, small mainly perivascular lymphocytic infiltrates with a predominance of CD8⁺ T cells, moderate microglial reaction, accumulation of SARS-CoV-2 S1 protein in the brain. The N protein of the virus was not detected in the brain. The most pronounced changes were observed in the brainstem, especially in the medulla oblongata, and the cerebellum. The severity of structural changes did not correlate with disease duration. S1 protein expression in the brain did not correlate with the severity of the microglial response or disease duration.

Conclusion: The identified neuropathological changes in COVID-19 in the acute and post-infectious phases are nonspecific with a predominance of vascular disorders and microglial reaction and are most pronounced in the brain stem and cerebellum. The SARS-CoV-2 S1 protein can accumulate in neurons and be detected in the brain a year or more after infection.