Brain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseases.

Autor: Agrawal S; Rush Alzheimer's Disease Center, Rush University Medical Center, Jelke Building, 1750 W. Harrison Street, Chicago, IL, 60612, USA. sonal_agrawal@rush.edu.; Department of Pathology, Rush University Medical Center, Chicago, IL, USA. sonal_agrawal@rush.edu., Farfel JM; Rush Alzheimer's Disease Center, Rush University Medical Center, Jelke Building, 1750 W. Harrison Street, Chicago, IL, 60612, USA.; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA., Arfanakis K; Rush Alzheimer's Disease Center, Rush University Medical Center, Jelke Building, 1750 W. Harrison Street, Chicago, IL, 60612, USA.; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA., Al-Harthi L; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA., Shull T; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA., Teppen TL; Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA., Evia AM; Rush Alzheimer's Disease Center, Rush University Medical Center, Jelke Building, 1750 W. Harrison Street, Chicago, IL, 60612, USA., Patel MB; Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN, USA.; Departments of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; The Geriatric Research Education Clinical Center (GRECC), Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System (TVHS), Nashville, TN, USA., Ely EW; Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN, USA.; Departments of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; The Geriatric Research Education Clinical Center (GRECC), Nashville Veterans Affairs Medical Center, Tennessee Valley Healthcare System (TVHS), Nashville, TN, USA., Leurgans SE; Rush Alzheimer's Disease Center, Rush University Medical Center, Jelke Building, 1750 W. Harrison Street, Chicago, IL, 60612, USA.; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA., Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Jelke Building, 1750 W. Harrison Street, Chicago, IL, 60612, USA.; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA., Mehta R; Rush Alzheimer's Disease Center, Rush University Medical Center, Jelke Building, 1750 W. Harrison Street, Chicago, IL, 60612, USA.; Department of Pathology, Rush University Medical Center, Chicago, IL, USA., Schneider JA; Rush Alzheimer's Disease Center, Rush University Medical Center, Jelke Building, 1750 W. Harrison Street, Chicago, IL, 60612, USA.; Department of Pathology, Rush University Medical Center, Chicago, IL, USA.; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2022 Dec 17; Vol. 10 (1), pp. 186. Date of Electronic Publication: 2022 Dec 17.
DOI: 10.1186/s40478-022-01493-7
Abstrakt: Background: This study examined neuropathological findings of patients who died following hospitalization in an intensive care unit with SARS-CoV-2.
Methods: Data originate from 20 decedents who underwent brain autopsy followed by ex-vivo imaging and dissection. Systematic neuropathologic examinations were performed to assess histopathologic changes including cerebrovascular disease and tissue injury, neurodegenerative diseases, and inflammatory response. Cerebrospinal fluid (CSF) and fixed tissues were evaluated for the presence of viral RNA and protein.
Results: The mean age-at-death was 66.2 years (range: 26-97 years) and 14 were male. The patient's medical history included cardiovascular risk factors or diseases (n = 11, 55%) and dementia (n = 5, 25%). Brain examination revealed a range of acute and chronic pathologies. Acute vascular pathologic changes were common in 16 (80%) subjects and included infarctions (n = 11, 55%) followed by acute hypoxic/ischemic injury (n = 9, 45%) and hemorrhages (n = 7, 35%). These acute pathologic changes were identified in both younger and older groups and those with and without vascular risk factors or diseases. Moderate-to-severe microglial activation were noted in 16 (80%) brains, while moderate-to-severe T lymphocyte accumulation was present in 5 (25%) brains. Encephalitis-like changes included lymphocytic cuffing (n = 6, 30%) and neuronophagia or microglial nodule (most prominent in the brainstem, n = 6, 30%) were also observed. A single brain showed vasculitis-like changes and one other exhibited foci of necrosis with ball-ring hemorrhages reminiscent of acute hemorrhagic leukoencephalopathy changes. Chronic pathologies were identified in only older decedents: 7 brains exhibited neurodegenerative diseases and 8 brains showed vascular disease pathologies. CSF and brain samples did not show evidence of viral RNA or protein.
Conclusions: Acute tissue injuries and microglial activation were the most common abnormalities in COVID-19 brains. Focal evidence of encephalitis-like changes was noted despite the lack of detectable virus. The majority of older subjects showed age-related brain pathologies even in the absence of known neurologic disease. Findings of this study suggest that acute brain injury superimposed on common pre-existing brain disease may put older subjects at higher risk of post-COVID neurologic sequelae.
(© 2022. The Author(s).)
Databáze: MEDLINE
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