@article{4529e4f55bf1402ea7f12f295aa9b491,
title = "SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19",
abstract = "Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, and S gene sequences detected one or more of these in OB in 8/21 subjects (38%). It is uncertain whether these RNA sequences represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), one with a large acute cerebral infarct and one with hemorrhagic encephalitis. Case-control RNAseq in OB and AMY found more than 5000 and 700 differentially expressed genes, respectively, unrelated to RT-PCR results; these involved immune response, neuronal constituents, and olfactory/taste receptor genes. Olfactory marker protein-1 reduction indicated COVID-19-related loss of OB olfactory mucosa afferents. Iba-1-immunoreactive microglia had reduced area fractions in cerebellar cortex and AMY, and cytokine arrays showed generalized downregulation in AMY and upregulation in blood serum in COVID-19 cases. Although OB is a major brain portal for SARS-CoV-2, COVID-19 brain changes are more likely due to blood-borne immune mediators and trans-synaptic gene expression changes arising from OB deafferentation.",
keywords = "Amygdala, Cytokine, Deafferentation, Encephalitis, Microglia, Olfactory bulb, SARS-Cov-2",
author = "Serrano, {Geidy E.} and Walker, {Jessica E.} and C{\'e}cilia Tremblay and Piras, {Ignazio S.} and Huentelman, {Matthew J.} and Belden, {Christine M.} and Danielle Goldfarb and David Shprecher and Alireza Atri and Adler, {Charles H.} and Shill, {Holly A.} and Erika Driver-Dunckley and Mehta, {Shyamal H.} and Richard Caselli and Woodruff, {Bryan K.} and Haarer, {Chadwick F.} and Thomas Ruhlen and Maria Torres and Steve Nguyen and Dasan Schmitt and Rapscak, {Steven Z.} and Christian Bime and Peters, {Joseph L.} and Ellie Alevritis and Arce, {Richard A.} and Glass, {Michael J.} and Daisy Vargas and Sue, {Lucia I.} and Intorcia, {Anthony J.} and Nelson, {Courtney M.} and Javon Oliver and Aryck Russell and Suszczewicz, {Katsuko E.} and Borja, {Claryssa I.} and Cline, {Madison P.} and Hemmingsen, {Spencer J.} and Sanaria Qiji and Hobgood, {Holly M.} and Mizgerd, {Joseph P.} and Sahoo, {Malaya K.} and Haiyu Zhang and Daniel Solis and Montine, {Thomas J.} and Berry, {Gerald J.} and Reiman, {Eric M.} and Katharina R{\"o}ltgen and Boyd, {Scott D.} and Pinsky, {Benjamin A.} and Zehnder, {James L.} and Pierre Talbot and Marc Desforges and Michael Deture and Dickson, {Dennis W.} and Beach, {Thomas G.}",
note = "Funding Information: This project was supported by a COVID-19 Supplement to a National Institute on Aging grant (3P30AG019610-20S1), submitted in response to a Notice of Special Interest (NOSI) issued by the National Institute on Aging (NOT-AG-20-022). Other support was provided by National Institute on Aging grants P30AG19610 and P30AG072980 to the Arizona Alzheimer's Disease Research Center. Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved.",
year = "2022",
month = sep,
day = "1",
doi = "10.1093/jnen/nlac056",
language = "English (US)",
volume = "81",
pages = "666--695",
journal = "Journal of Neuropathology and Experimental Neurology",
issn = "0022-3069",
number = "9",
}