Citations 1
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 , Huentelman, Matthew J. , Belden, Christine M. , Goldfarb, Danielle, Shill, Holly A. , Driver‐Dunckley, Erika , Mehta, Shyamal H. , Caselli, Richard J. , Woodruff, Bryan K. , Haarer, Chadwick F., Ruhlen, Thomas, Nguyen, Steve, Schmitt, Dasan, Rapscak, Steven Z., Bime, Christian , Peters, Joseph L., Alevritis, Ellie, Arce, Richard, 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 H., Hobgood, Holly M, Zhang, Haiyu , Solis, Daniel , Montine, Thomas J. , Berry, Gerald J. , Reiman, Eric M. , Röltgen, Katharina , Boyd, Scott D. , Zehnder, James L. , Desforges, Marc , DeTure, Michael , Beach, Thomas G. , Driver-Dunckley, Erika, Berry, Gerald J , Serrano, Geidy E , Piras, Ignazio Stefano , Shprecher, David , Atri, Alireza , Adler, Charles H. , Haarer, Chadwick F., Torres, Marı́a José , Peters, Joseph L, Mizgerd, Joseph P. , Sahoo, Malaya Kumar , Pinsky, Benjamin A. , Talbot, Pierre J. , Dickson, Dennis W.
Journal of Neuropathology & Experimental Neurology | July 12, 2022 | Volume: 81 | Issue: 9 | Pages: 666-695
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.