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

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),...

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Published inJournal of neuropathology and experimental neurology Vol. 81; no. 9; pp. 666 - 695
Main 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
Format Journal Article
LanguageEnglish
Published England Oxford University Press 01.09.2022
Subjects
Amygdala
Biological products
Brain
Brain diseases
Coronaviruses
COVID-19
Diagnosis
Gene Expression
Genes
Genetic aspects
Health aspects
Histochemistry
Histopathology
Humans
Immunity
Immunomodulators
Neurological research
Neurons
Original
Risk factors
RNA
RNA polymerase
RNA sequencing
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
United States
Canada
Maryland
Arizona
Encephalitis
SARS-Cov-2
Amygdala
Cytokine
Olfactory bulb
Deafferentation
Microglia
Online AccessGet full text

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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.
AbstractList 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.
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. Key Words: Amygdala, Cytokine, Deafferentation, Encephalitis, Microglia, Olfactory bulb, SARS-Cov-2.
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.
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.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.
Audience Academic
Author Adler, Charles H
Montine, Thomas J
Piras, Ignazio S
Driver-Dunckley, Erika
Oliver, Javon
Suszczewicz, Katsuko E
Walker, Jessica E
Shprecher, David
Glass, Michael J
Nguyen, Steve
Boyd, Scott D
Mizgerd, Joseph P
Nelson, Courtney M
Intorcia, Anthony J
Ruhlen, Thomas
Peters, Joseph L
Berry, Gerald J
Shill, Holly A
Solis, Daniel
Desforges, Marc
Hemmingsen, Spencer J
Pinsky, Benjamin A
Rapscak, Steven Z
Talbot, Pierre
Hobgood, Holly M
Dickson, Dennis W
Serrano, Geidy E
Goldfarb, Danielle
Cline, Madison P
DeTure, Michael
Beach, Thomas G
Bime, Christian
Sue, Lucia I
Caselli, Richard
Zehnder, James L
Reiman, Eric M
Vargas, Daisy
Tremblay, Cécilia
Qiji, Sanaria
Belden, Christine M
Zhang, Haiyu
Woodruff, Bryan K
Mehta, Shyamal H
Haarer, Chadwick F
Alevritis, Ellie
Borja, Claryssa I
Röltgen, Katharina
Huentelman, Matthew J
Torres, Maria
Schmitt, Dasan
Atri, Alireza
Sahoo, Malaya K
Arce, Richard A
Russell, Aryck
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35818336$$D View this record in MEDLINE/PubMed
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Keywords Encephalitis
SARS-Cov-2
Amygdala
Cytokine
Olfactory bulb
Deafferentation
Microglia
Language English
License This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
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Geidy E. Serrano and Thomas G. Beach contributed equally to this work.
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PublicationTitle Journal of neuropathology and experimental neurology
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Snippet 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...
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...
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StartPage 666
SubjectTerms Amygdala
Biological products
Brain
Brain diseases
Coronaviruses
COVID-19
Diagnosis
Gene Expression
Genes
Genetic aspects
Health aspects
Histochemistry
Histopathology
Humans
Immunity
Immunomodulators
Neurological research
Neurons
Original
Risk factors
RNA
RNA polymerase
RNA sequencing
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Title SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19
URI https://www.ncbi.nlm.nih.gov/pubmed/35818336
https://www.proquest.com/docview/2707763449
https://www.proquest.com/docview/2688522004
https://pubmed.ncbi.nlm.nih.gov/PMC9278252
Volume 81
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