Evidence map›Paper›PMID 41499397›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Combination antiviral and anti-inflammatory therapy mitigates persistent neurological deficits in mice post SARS-CoV-2 infection.

Abhishek Kumar Verma, Lu Tan, Noah Schuster, Skyler L Moye, Li-Chun Lin, Shea Lowery, Eazhisaivallabi Duraisami, Juan E Abrahante Lloréns, Qiang Qiu, Marco Hefti and 5 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

15 authors.

Abhishek Kumar VermaDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242.ORCID 0000-0002-6816-2378
Lu TanDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242.
Noah SchusterDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242.
Skyler L MoyeDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242.
Li-Chun LinIowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242.
Shea LoweryDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 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 55455.
Qiang QiuDepartment of Cell Biology and Physiology, Stowers Institute for Medical Research, Kansas City, MO 64110.
Marco HeftiDepartment of Pathology, University of Iowa, Iowa City, IA 52242.
David K MeyerholzDepartment of Pathology, University of Iowa, Iowa City, IA 52242.ORCID 0000-0003-1552-3253
Mitchell C ColemanDepartment of Orthopedics and Rehabilitation, University of Iowa, Iowa City, IA 52242.
C Ron YuDepartment of Cell Biology and Physiology, Stowers Institute for Medical Research, Kansas City, MO 64110.
Mark W AlbersDepartment of Neurology, Harvard Medical School, Boston, MA 02114.
Stanley PerlmanDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242.ORCID 0000-0003-4213-2354

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
Training in Molecular Virology, Viral Pathogenesis and Viral VectorsT32AI007533 · NIAID · UNIVERSITY OF IOWA · PI Stanley Perlman · 1998 to 2026
$2.5M
HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01 NS36592HHS | NIH | National Institute on Aging (NIA) RF1 AG078297NIAID NIH HHS P01 AI060699NIAID NIH HHS R01 AI129269NIAID NIH HHS T32 AI007533NINDS NIH HHS R01 NS036592
6 · The paper itself

Abstract

Post-acute sequelae of COVID-19 (PASC) encompasses persistent neurological disease, including olfactory and cognitive dysfunction. The basis for this dysfunction is poorly understood. Here, we report neurological dysfunction for at least 120 d postinfection in mice infected with a virulent nonneurotropic mouse-adapted SARS-CoV-2. Long after recovery from nasal infection, we observed diminished tyrosine hydroxylase expression in olfactory bulb glomeruli and in substantia nigra. Similar changes were observed in brains of COVID-19 deceased patients. Vulnerability of dopaminergic neurons in these brain areas was accompanied by increased proinflammatory cytokines, and neurobehavioral changes. RNAseq analysis unveiled persistent microglia activation, similar to human neurodegenerative diseases. Treatment with antivirals (nirmatrelvir and molnupiravir) at the time of infection minimally prevented neurological abnormalities, consistent with patient data. In contrast, antivirals plus corticosteroids resulted in nearly complete recovery of neurological function. Remarkably, initiation of combined therapy even three days after infection improved outcomes. Together these results demonstrate that neurological dysfunction in SARS-CoV-2 infected mice resembles human neurodegenerative disease and indicate that minimizing inflammation early after SARS-CoV-2 infection may be critical for decreasing neurological PASC. The requirement for decreasing inflammation soon after infection may also explain why antiviral therapy has had inconsistent effects in patients.

Indexed as

Anti-Inflammatory AgentsAntiviral AgentsCOVID-19COVID-19 Drug TreatmentNervous System DiseasesAnimalsCytokinesDisease Models, AnimalDopaminergic NeuronsDrug Therapy, CombinationFemaleHumansMaleMiceMicrogliaOlfactory BulbAnti-Inflammatory AgentsAntiviral AgentsCytokinesantivirallong-COVIDmicroglianeuroimmunologySARS-CoV-2

Identifiers

PMID41499397
PMCPMC12799161

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.