{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:30:22Z","timestamp":1790213422925,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["A5555"],"award-info":[{"award-number":["A5555"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune responses and peroxisome biogenesis factors during severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infection using a multiplatform strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Brain tissues from coronavirus disease 2019 (COVID\u201019) (n\u2009=\u200912) and other disease control (ODC) (n\u2009=\u200912) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS\u2010CoV\u20102, were investigated by droplet digital polymerase chain reaction (ddPCR), quantitative reverse transcriptase PCR (RT\u2010qPCR), and immunodetection methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SARS\u2010CoV\u20102 RNA was detected in the CNS of 4 patients with COVID\u201019 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID\u201019 showed induction of pro\u2010inflammatory transcripts (<jats:italic>IL8, IL18, CXCL10, NOD2<\/jats:italic>) and cytokines (GM\u2010CSF and IL\u201018) compared to CNS tissues from ODC patients (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Peroxisome biogenesis factor transcripts (<jats:italic>PEX3, PEX5L, PEX11\u03b2,<\/jats:italic> and <jats:italic>PEX14<\/jats:italic>) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID\u201019 compared to ODC patients (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). SARS\u2010CoV\u20102 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post\u2010infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post\u2010infection (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). <jats:italic>Pex3<\/jats:italic> transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS\u2010CoV\u20102 infected animals (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>COVID\u201019 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS\u2010CoV\u20102 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post\u2010acute sequelae of COVID\u201019. 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