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: COVID-19; dementia; elderly; microglia; neurocognitive disorders; neuropathology.
【저자키워드】 COVID-19, elderly, Dementia, microglia, neuropathology., neurocognitive disorders, 【초록키워드】 coronavirus disease, SARS-CoV-2, immunohistochemistry, pathology, Coronavirus disease 2019, Lymphocytes, adaptive, Immunity, mechanical ventilation, Innate immunity, SARS-COV-2 infection, Infection, Brain, Encephalitis, hippocampus, Endothelium, lymphopenia, lymphocyte, Dementia, Clinical course, Neuropathology, delirium, Patient, Neuroinflammation, Control, age, Brainstem, microglia, disease, change, neurodegeneration, astrocytes, Evidence, COVID-19 cases, COVID-19 patient, brain damage, evidence of, determined by, Activation, disorders, COVID-19 case, Stage, disorder, finding, CD68, positive, Hyperactivation, brains, controls, highlight, greater, analyzed, detect, lack, significantly, detectable, applied, undergo, appear, conditions, semi-quantitative, microglial, cortical, alterations, small vessel, the SARS-CoV-2, 【제목키워드】 Activation, microglial,