Evidence map›Paper›PMID 37645925›Full record

ArticlebioRxiv : the preprint server for biology2023

Impact of age and sex on neuroinflammation following SARS-CoV-2 infection in a murine model.

Venkatramana D Krishna, Allison Chang, Holly Korthas, Susanna R Var, Walter C Low, Ling Li, Maxim C-J Cheeran

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Venkatramana D KrishnaDepartment of Veterinary Population Medicine, University of Minnesota, Saint Paul, MN 55108, USA.
Allison ChangGraduate Program in Neuroscience.
Holly KorthasDepartment of Experimental and Clinical Pharmacology.
Susanna R VarDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Walter C LowGraduate Program in Neuroscience.
Ling LiGraduate Program in Neuroscience.
Maxim C-J CheeranDepartment of Veterinary Population Medicine, University of Minnesota, Saint Paul, MN 55108, USA.
University of Minnesota · US

Funding

Acute and Long-Term Impact of SARS-CoV-2 Infection and its Interaction with APOE on Cognitive Function and Neuropathology in Aging and Alzheimer's DiseaseRF1AG077772 · NIA · UNIVERSITY OF MINNESOTA · PI CHEERAN, MAXIM CHACKO-JOSEPH, LI, LING · 2022 to 2022
$2.2M
HDL Mimetic Peptide-Mediated Enhancement of Neurovascular Function to Mitigate Cerebral Amyloid Angiopathy and Alzheimer's DiseaseRF1AG058081 · NIA · UNIVERSITY OF MINNESOTA · PI LI, LING · 2018 to 2018
$1.9M
NIA NIH HHS RF1 AG058081NIA NIH HHS RF1 AG077772
6 · The paper itself

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for the worldwide COVID-19 pandemic, is known to infect people of all ages and both sexes. Senior populations have the greatest risk of severe disease, and sexual dimorphism in clinical outcomes has been reported in COVID-19. SARS-CoV-2 infection in humans can cause damage to multiple organ systems, including the brain. Neurological symptoms are widely observed in patients with COVID-19, with many survivors suffering from persistent neurological and cognitive impairment, potentially accelerating Alzheimer's disease. The present study aims to investigate the impact of age and sex on the neuroinflammatory response to SARS-CoV-2 infection using a mouse model. Wild-type C57BL/6 mice were inoculated, by intranasal route, with SARS-CoV-2 lineage B.1.351 variant known to infect mice. Older animals and in particular males exhibited a significantly greater weight loss starting at 4 dpi. In addition, male animals exhibited higher viral RNA loads and higher titers of infectious virus in the lung, which was particularly evident in males at 16 months of age. Notably, no viral RNA was detected in the brains of infected mice, regardless of age or sex. Nevertheless, expression of IL-6, TNF-α, and CCL-2 in the lung and brain was increased with viral infection. An unbiased brain RNA-seq/transcriptomic analysis showed that SARS-CoV-2 infection caused significant changes in gene expression profiles in the brain, with innate immunity, defense response to virus, cerebravascular and neuronal functions, as the major molecular networks affected. The data presented in this study show that SARS-CoV-2 infection triggers a neuroinflammatory response despite the lack of detectable virus in the brain. Age and sex have a modifying effect on this pathogenic process. Aberrant activation of innate immune response, disruption of blood-brain barrier and endothelial cell integrity, and supression of neuronal activity and axonogenesis underlie the impact of SARS-CoV-2 infection on the brain. Understanding the role of these affected pathways in SARS-CoV-2 pathogenesis helps identify appropriate points of therapeutic interventions to alleviate neurological dysfunction observed during COVID-19.

Indexed as

brainCOVID-19mouse modelneuroinflammationSARS-CoV-2transcriptomics

Identifiers

PMID37645925
PMCPMC10462071
OpenAlexW4385803504

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.