Brain histopathological changes caused by SARS-CoV-2 infection

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affected over 775 million people in 232 countries and regions between 2020 and 2024, causing over seven million deaths and becoming the largest pandemic of the 21st century. Initially considered a respiratory virus with various clinical forms (from asymptomatic to severe clinical forms with severe respiratory failure), it was later shown that the disease also affects other organs and systems, including the nervous system. Therefore, in this study, we aimed at highlighting the histopathological lesions present in the central nervous system (CNS) in patients who died from SARS-CoV-2 infection. For microscopic study, 65 brain fragments were collected from 36 patients infected with SARS-CoV-2, clinically, imaging, and biologically diagnosed with COVID-19 [by real-time reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2]. The patients died under suspicious circumstances from a forensic medicine perspective during 2020 and required autopsy at the Institute of Forensic Medicine, Craiova or the Mina Minovici National Institute of Forensic Medicine, Bucharest, Romania to determine the main causes of death. The most common brain lesions were ischemic, with the aspect of neurons with intensely eosinophilic cytoplasm ("red neurons"), condensed, pyknotic, hyperchromic nuclei, perineuronal edema, giving the cerebral cortex a "spongy" appearance, fragmentation of unmyelinated extensions in the neuropil, collapse of blood vessels, and perivascular edema. Multiple vascular thromboses were identified, predominantly in small vessels (capillaries, arterioles, venules) or destruction of endothelial cells (ECs) with increased blood-brain barrier (BBB) permeability, perivascular edema, and collapse of blood vessels or areas of intracranial hemorrhage. The anti-spike antibody showed that the SARS-CoV-2 infected large neurons (pyramidal cells in the cerebral cortex and Purkinje cells in the cerebellar hemispheres), ECs, pericytes, and even smooth muscle cells in the structure of arterioles, metarterioles, and venules.