Evidence map›Paper›PMID 38895239›Full record

ArticlebioRxiv : the preprint server for biology2024

Persistent Neurological Deficits in Mouse PASC Reveal Antiviral Drug Limitations.

Abhishek Kumar Verma, Shea Lowery, Li-Chin Lin, Eazhisaivallabi Duraisami, Juan E Abrahante Lloréns, Qiang Qiu, Marco Hefti, C Ron Yu, Mark W Albers, Stanley Perlman

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Abhishek Kumar VermaDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242.
Shea LoweryDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242.
Li-Chin LinIowa Neuroscience Institute, University of Iowa, IA, USA 52242.
Eazhisaivallabi DuraisamiDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242.
Juan E Abrahante LlorénsMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN.
Qiang QiuStowers Institute for Medical Research, Kansas City, MO 64110.
Marco HeftiDepartment of Pathology, University of Iowa, Iowa City, IA 52242.
C Ron YuStowers Institute for Medical Research, Kansas City, MO 64110.
Mark W AlbersDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-7855-3455
Stanley PerlmanDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242.

Funding

SARS-CoV Proteins in Heterologous Viral InfectionP01AI060699 · NIAID · UNIVERSITY OF IOWA · PI PERLMAN, STANLEY · 2004 to 2021
$21.5M
Role of microglia in MHV-induced demyelinationR01NS036592 · NINDS · UNIVERSITY OF IOWA · PI PERLMAN, STANLEY · 1997 to 2021
$6.0M
Role of eicosanoids in pathogenic human CoV infectionsR01AI129269 · NIAID · UNIVERSITY OF IOWA · PI Stanley Perlman · 2016 to 2026
$4.7M
A non-canonical role for tau in early human brain developmentR01NS136448 · NINDS · UNIVERSITY OF IOWA · PI Marco Matthias Hefti · 2024 to 2026
$1.6M
Novel tau-based diagnostics for neonatal hypoxic-ischemic injuryK23NS109284 · NINDS · UNIVERSITY OF IOWA · PI HEFTI, MARCO MATTHIAS · 2019 to 2023
$950k
NIAID NIH HHS P01 AI060699NIAID NIH HHS R01 AI129269NINDS NIH HHS K23 NS109284NINDS NIH HHS R01 NS036592NINDS NIH HHS R01 NS136448
6 · The paper itself

Abstract

Post-Acute Sequelae of COVID-19 (PASC) encompasses persistent neurological symptoms, including olfactory and autonomic dysfunction. Here, we report chronic neurological dysfunction in mice infected with a virulent mouse-adapted SARS-CoV-2 that does not infect the brain. Long after recovery from nasal infection, we observed loss of tyrosine hydroxylase (TH) expression in olfactory bulb glomeruli and neurotransmitter levels in the substantia nigra (SN) persisted. Vulnerability of dopaminergic neurons in these brain areas was accompanied by increased levels of proinflammatory cytokines and neurobehavioral changes. RNAseq analysis unveiled persistent microglia activation, as found in human neurodegenerative diseases. Early treatment with antivirals (nirmatrelvir and molnupiravir) reduced virus titers and lung inflammation but failed to prevent neurological abnormalities, as observed in patients. Together these results show that chronic deficiencies in neuronal function in SARS-CoV-2-infected mice are not directly linked to ongoing olfactory epithelium dysfunction. Rather, they bear similarity with neurodegenerative disease, the vulnerability of which is exacerbated by chronic inflammation.

Indexed as

AnosmiaBrainInflammationMicrogliaNeurodegenerationOlfactory BulbSARS-CoV-2Substantia NigraTyrosine Hydroxylase

Identifiers

PMID38895239
PMCPMC11185538

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.