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Record W4285036763 · doi:10.1093/jnen/nlac056

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

2022· article· en· W4285036763 on OpenAlexaff
Geidy E. Serrano, Jessica E. Walker, Cécilia Tremblay, Ignazio S. Piras, Matthew J. Huentelman, Christine M. Belden, Danielle Goldfarb, David Shprecher, Alireza Atri, Charles H. Adler, Holly A. Shill, Erika Driver‐Dunckley, Shyamal H. Mehta, Richard J. Caselli, Bryan K. Woodruff, Chadwick F. Haarer, Thomas Ruhlen, Marı́a José Torres, Steve Nguyen, Dasan Schmitt, Steven Z. Rapscak, Christian Bime, Joseph L. Peters, Ellie Alevritis, Richard Arce, Michael J. Glass, Daisy Vargas, Lucia I. Sue, Anthony J. Intorcia, Courtney M. Nelson, Javon Oliver, Aryck Russell, Katsuko E. Suszczewicz, Claryssa I. Borja, Madison P. Cline, Spencer J Hemmingsen, Sanaria H. Qiji, Holly M Hobgood, Joseph P. Mizgerd, Malaya K. Sahoo, Haiyu Zhang, Daniel Solis, Thomas J. Montine, Gerald J. Berry, Eric M. Reiman, Katharina Röltgen, Scott D. Boyd, Benjamin A. Pinsky, James L. Zehnder, Pierre J. Talbot, Marc Desforges, Michael DeTure, Dennis W. Dickson, Thomas G. Beach

Bibliographic record

VenueJournal of Neuropathology & Experimental Neurology · 2022
Typearticle
Languageen
FieldMedicine
TopicLong-Term Effects of COVID-19
Canadian institutionsUniversité de MontréalCentre Hospitalier Universitaire Sainte-JustineInstitut National de la Recherche Scientifique
FundersNational Heart, Lung, and Blood InstituteNational Institute on Aging
KeywordsOlfactory bulbBiologyDownregulation and upregulationImmune systemGeneHistopathologyEntorhinal cortexGene expressionPathologyReal-time polymerase chain reactionVirologyImmunologyMedicineHippocampusCentral nervous systemEndocrinologyGenetics

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.434
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.312
Teacher spread0.290 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations47
Published2022
Admission routes1
Has abstractyes

Explore more

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