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.
【저자키워드】 cytokine, Encephalitis, SARS-CoV-2., olfactory bulb, microglia, Amygdala, Deafferentation, 【초록키워드】 COVID-19, SARS-CoV-2, immune response, Gene Expression, RT-PCR, virus, Autopsy, immune, Brain, Encephalitis, Histopathology, serum, Region, olfactory bulb, Control, RNA-dependent RNA polymerase, RNAseq, receptor, microglia, RNA polymerase, change, Differentially expressed genes, Blood, marker, S gene, Amygdala, Deafferentation, COVID-19 cases, olfactory, mucosa, Autopsies, portal, reduction, Hemorrhagic, Non-COVID-19, subject, sequence, upregulation, fraction, downregulation, RNA sequences, brains, RNA sequence, Genes, SARS-CoV-2 E gene, cerebellar cortex, hemorrhagic encephalitis, viral sequence, involved, indicated, reduced, arising, Significant, neuronal, 【제목키워드】 SARS-CoV-2, detection, change, Regional, with COVID-19,