Morphological features of brain damage in severe COVID-19

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Abstract

Background: The damage to the nervous system in COVID-19 reflects the systemic nature of the infection. The question of the neuroinvasive potential of SARS-CoV-2 remains open, the role of "pseudovirions" in the development of the endothelial dysfunction, as well as of the S1 subunit in the TLR activation, and the importance of the blood-brain barrier are discussed. The immunological, non-immunological, and cytopathic mechanisms of the virus's action are described; there is no clear understanding of the genesis of neuropathological changes caused by SARS-CoV-2. In this tragic pandemic, the lessons of the dead should help save lives and health.

Aim: to study and explain the features of brain damage in COVID-19.

Methods: Brain fragments from 20 patients who died due to severe COVID-19 were studied, the sections were stained with hematoxylin and eosin, according to van Gieson and Nissl, IHC reactions were performed with antibodies to the S-protein, CD68 and CD8, the changes were compared with those related to the lethal outcomes of pancreatic necrosis and ruptured aortic aneurysm.

Results: The following changes in the olfactory analyzer were revealed: sharp edema, dystrophic changes in neurons, gliosis, accumulations of starchy bodies, which explains the neuronal pathway of SARS-CoV-2 invasion; vascular plethora, erythrostasis and thrombosis, perivenular hemorrhages, diffuse edema, macroglia proliferation, perivascular astrocytosis and satellite. A positive reaction with the antibodies to the S1 and S2 subunits of the spike protein was detected, while the result of the reaction with antibodies to the N-protein of the virus, confirming the active replication of the virus, was doubtful. The S-protein expression in individual endotheliocytes makes the transendothelial route of the virus entry unlikely, in contrast to the hematogenous and neuronal pathways. The viral DNA was not detected by PCR. A weak inflammatory reaction was revealed in the form of perivascular accumulations of lymphocytes, scattered T-lymphocytes.

Conclusions: 2 groups of changes were identified, the first group included circulatory disorders with a tendency to thrombosis, edema, dystrophic-necrotic changes in neurons, glial proliferation, the second group included inflammatory-degenerative changes, a weak inflammatory reaction and amyloid-like bodies. Further morphometric and statistical studies are needed to obtain the reliable conclusions.

About the authors

Aleksander A. Kanibolotskiy

N.V. Sklifosovsky Research Institute for Emergency Medicine; Research Institute for Healthcare Organization and Medical Management

Author for correspondence.
Email: dr.kaa@mail.ru
SPIN-code: 3976-1662

врач-патологоанатом патологоанатомического отделения, заведующий  организационно-методическим отделом по патологической анатомии

Russian Federation, Moscow; Moscow

Oleg V. Zayratyants

Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Email: ovzair@mail.ru
ORCID iD: 0000-0003-3606-3823
SPIN-code: 4817-1084

MD, PhD, Professor

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Brain, hematoxylin and eosin stained section shows hyperemia, erythrocyte stasis in capillary vessels, scale bar 50 µm.

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3. Fig. 2. Brain, edema with spongioform changes. Hematoxylin and eosin staining, scale bar 100 µm.

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4. Fig. 3. Brain, ischemic damage like signs of necrosis and cytolysis of neurons. Hematoxylin and eosin staining, scale bar 50 µm.

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5. Fig. 4. Brain, perineuronal satelliteosis (arrows). Hematoxylin and eosin staining, scale bar 50 µm.

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6. Fig. 5. Brain, positive immunohistochemical reaction with antibodies to the S1 subunit of the SARS-CoV-2 spike protein in neurons and astrocytes. Scale bar 50 µm.

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7. Fig. 6. Brain, positive immunohistochemical reaction with antibodies to CD68. Hematoxylin and eosin staining, scale bar 50 µm.

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8. Fig. 7. Brain, positive immunohistochemical reaction with antibodies to CD8. Hematoxylin and eosin staining, scale bar 50 µm.

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9. Fig. 8. Brain, numerous сorpora amylacea. Hematoxylin and eosin staining, scale bar 100 µm.

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Copyright (c) 2023 Kanibolotskiy A.A., Zayratyants O.V.

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