SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19.
Amygdala
Cytokine
Deafferentation
Encephalitis
Microglia
Olfactory bulb
SARS-Cov-2
Journal
Journal of neuropathology and experimental neurology
ISSN: 1554-6578
Titre abrégé: J Neuropathol Exp Neurol
Pays: England
ID NLM: 2985192R
Informations de publication
Date de publication:
16 08 2022
16 08 2022
Historique:
pubmed:
13
7
2022
medline:
24
8
2022
entrez:
12
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35818336
pii: 6639867
doi: 10.1093/jnen/nlac056
pmc: PMC9278252
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
666-695Subventions
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072980
Pays : United States
Organisme : NHLBI NIH HHS
ID : R33 HL137081
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135756
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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