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

dc.contributor.authorAgrawal, Sonal
dc.contributor.authorFarfel, Jose M.
dc.contributor.authorArfanakis, Konstantinos
dc.contributor.authorAl-Harthi, Lena
dc.contributor.authorShull, Tanner
dc.contributor.authorTeppen, Tara L.
dc.contributor.authorEvia, Arnold M.
dc.contributor.authorPatel, Mayur B.
dc.contributor.authorEly, E. Wesley
dc.contributor.authorLeurgans, Sue. E.
dc.contributor.authorBennett, David A.
dc.contributor.authorMehta, Rupal
dc.contributor.authorSchneider, Julie A.
dc.identifier.otherPubMed ID36528671
dc.description.abstractBackground: 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 cerebro-vascular 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.en_US
dc.description.sponsorshipThe study is funded by the National Institute on Aging Grants Nos. (R01AG058639 and R01AG058639‑02S2).en_US
dc.publisherActa Neuropathologica Communicationsen_US
dc.rights© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver (http://creativeco applies to the data made available in this article, unless otherwise stated in a credit line to the data.
dc.subjectSevere acute respiratory syndrome coronavirus 2en_US
dc.subjectAcute hemorrhagic leukoencephalopathyen_US
dc.titleBrain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseasesen_US

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