COVID-19-related neuropathology and microglial activation in elderly with and without dementia.
Brain Pathol
; 31(5): e12997, 2021 09.
Article
in English
| MEDLINE | ID: covidwho-1273078
ABSTRACT
The actual role of SARS-CoV-2 in brain damage remains controversial due to lack of matched controls. We aim to highlight to what extent is neuropathology determined by SARS-CoV-2 or by pre-existing conditions. Findings of 9 Coronavirus disease 2019 (COVID-19) cases and 6 matched non-COVID controls (mean age 79 y/o) were compared. Brains were analyzed through immunohistochemistry to detect SARS-CoV-2, lymphocytes, astrocytes, endothelium, and microglia. A semi-quantitative scoring was applied to grade microglial activation. Thal-Braak stages and the presence of small vessel disease were determined in all cases. COVID-19 cases had a relatively short clinical course (0-32 days; mean 10 days), and did not undergo mechanical ventilation. Five patients with neurocognitive disorder had delirium. All COVID-19 cases showed non-SARS-CoV-2-specific changes including hypoxic-agonal alterations, and a variable degree of neurodegeneration and/or pre-existent SVD. The neuroinflammatory picture was dominated by ameboid CD68 positive microglia, while only scant lymphocytic presence and very few traces of SARS-CoV-2 were detected. Microglial activation in the brainstem was significantly greater in COVID-19 cases (p = 0.046). Instead, microglial hyperactivation in the frontal cortex and hippocampus was clearly associated to AD pathology (p = 0.001), regardless of the SARS-CoV-2 infection. In COVID-19 cases complicated by delirium (all with neurocognitive disorders), there was a significant enhancement of microglia in the hippocampus (p = 0.048). Although higher in cases with both Alzheimer's pathology and COVID-19, cortical neuroinflammation is not related to COVID-19 per se but mostly to pre-existing neurodegeneration. COVID-19 brains seem to manifest a boosting of innate immunity with microglial reinforcement, and adaptive immunity suppression with low number of brain lymphocytes probably related to systemic lymphopenia. Thus, no neuropathological evidence of SARS-CoV-2-specific encephalitis is detectable. The microglial hyperactivation in the brainstem, and in the hippocampus of COVID-19 patients with delirium, appears as a specific topographical phenomenon, and probably represents the neuropathological basis of the "COVID-19 encephalopathic syndrome" in the elderly.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Microglia
/
Dementia
/
COVID-19
/
Nervous System Diseases
Type of study:
Observational study
/
Prognostic study
/
Qualitative research
Limits:
Aged
/
Female
/
Humans
/
Male
Language:
English
Journal:
Brain Pathol
Journal subject:
Brain
/
Pathology
Year:
2021
Document Type:
Article
Affiliation country:
Bpa.12997
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