Brain histopathological changes caused by SARS-CoV-2 infection.

Area of Science:

• Neuropathology
• Infectious Diseases
• Forensic Medicine

Background:

• Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a significant global pandemic.
• While initially recognized as a respiratory illness, SARS-CoV-2 has been increasingly associated with neurological manifestations and systemic effects.
• Understanding the neuropathological consequences of SARS-CoV-2 infection is crucial for comprehending disease severity and patient outcomes.

Purpose of the Study:

• To investigate and characterize the histopathological lesions in the central nervous system (CNS) of individuals who died from SARS-CoV-2 infection.
• To correlate clinical and biological diagnoses of COVID-19 with observed brain pathologies.
• To identify specific cellular targets of SARS-CoV-2 within the CNS.

Main Methods:

• Microscopic examination of 65 brain tissue fragments from 36 patients diagnosed with COVID-19 via RT-PCR.
• Autopsy was performed for forensic medicine purposes to determine the cause of death in cases with suspicious circumstances.
• Immunohistochemistry using anti-spike antibodies to detect viral presence in neural and vascular tissues.

Main Results:

• The most frequent CNS lesions included ischemic changes, characterized by 'red neurons,' perineuronal edema, and a 'spongy' appearance of the cerebral cortex.
• Multiple vascular thromboses, particularly in small vessels, endothelial cell destruction, increased blood-brain barrier permeability, and intracranial hemorrhages were observed.
• Anti-spike antibody staining confirmed SARS-CoV-2 infection in large neurons (cortical pyramidal cells, cerebellar Purkinje cells), endothelial cells, pericytes, and vascular smooth muscle cells.

Conclusions:

• SARS-CoV-2 infection leads to significant histopathological damage in the central nervous system, extending beyond respiratory symptoms.
• Ischemic injury and vascular pathology, including thrombosis and blood-brain barrier disruption, are key features of COVID-19 neuropathology.
• The virus directly infects various neural and vascular cell types within the brain, contributing to the observed lesions and potential neurological sequelae.