SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19. Issue 9 (11th July 2022)

• Record Type: Journal Article
• Authors: 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; Desforges, Marc; DeTure, Michael; Dickson, Dennis W; Beach, Thomas G;
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 81:Issue 9(2022)
• Page Start: 666
• Page End: 695
• Publication Date: 2022-07-11
• Subjects: Amygdala -- Cytokine -- Deafferentation -- Encephalitis -- Microglia -- Olfactory bulb -- SARS-Cov-2; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlac056
• Languages: English
• ISSNs: 0022-3069

Abstract

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.