Dépôt numérique

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19

Serrano, Geidy E; Walker, Jessica E; Tremblay, Cécilia; Piras, Ignazio S; Huentelman, Matthew J; Belden, Christine M; Goldfarb, Danielle; Shprecher, David; Atri, Alireza; Adler, Charles H; Shill, Holly A; Driver-Dunckley, Erika; Mehta, Shyamal H; Caselli, Richard; Woodruff, Bryan K; Haarer, Chadwick F; Ruhlen, Thomas; Torres, Maria; Nguyen, Steve; Schmitt, Dasan; Rapscak, Steven Z; Bime, Christian; Peters, Joseph L; Alevritis, Ellie; Arce, Richard A; Glass, Michael J; Vargas, Daisy; Sue, Lucia I; Intorcia, Anthony J; Nelson, Courtney M; Oliver, Javon; Russell, Aryck; Suszczewicz, Katsuko E; Borja, Claryssa I; Cline, Madison P; Hemmingsen, Spencer J; Qiji, Sanaria; Hobgood, Holly M; Mizgerd, Joseph P; Sahoo, Malaya K; Zhang, Haiyu; Solis, Daniel; Montine, Thomas J; Berry, Gerald J; Reiman, Eric M; Röltgen, Katharina; Boyd, Scott D; Pinsky, Benjamin A; Zehnder, James L; Talbot, Pierre J. ORCID logoORCID: https://orcid.org/0000-0003-4203-7744; Desforges, Marc; DeTure, Michael; Dickson, Dennis W et Beach, Thomas G (2022). SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19 Journal of Neuropathology and Experimental Neurology , vol. 81 , nº 9. pp. 666-695. DOI: 10.1093/jnen/nlac056.

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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.

Type de document: Article
Mots-clés libres: Amygdala; Cytokine; Deafferentation; Encephalitis; Microglia; Olfactory bulb; SARS-Cov-2.
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 11 déc. 2023 14:50
Dernière modification: 11 déc. 2023 14:50
URI: https://espace.inrs.ca/id/eprint/13474

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