Evidence map›Paper›PMID 35632761›Full record

ArticleViruses2022

Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse.

Frauke Seehusen, Jordan J Clark, Parul Sharma, Eleanor G Bentley, Adam Kirby, Krishanthi Subramaniam, Sabina Wunderlin-Giuliani, Grant L Hughes, Edward I Patterson, Benedict D Michael and 4 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Viruses, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05576714 (Investigation of Prognostic Biomarkers, Host Factors and Viral Factors for COVID-19 Associated Encephalopathy/Encephalitis and Multi-systemic Inflammatory Syndrome in Children), which is not on this map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
15.4field-weighted citation impact, top 1% of its field
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.

NCT05576714 unknown statusnot on this map

Investigation of Prognostic Biomarkers, Host Factors and Viral Factors for COVID-19 Associated Encephalopathy/Encephalitis and Multi-systemic Inflammatory Syndrome in Children

Typeobservational_patient_registrySponsorNational Taiwan University HospitalRan2022 to 2025Enrolled300ConditionsCOVID-19-Associated Encephalitis, Multisystem Inflammatory Syndrome in ChildrenArmsdelineate its prognostic biomarker, host genetic factors, immunopathogenesis and viral pathogenesis
3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 123 citations in OpenAlex.

  1. Article
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  15. Phlorotannin-RichViruses · 2024
    Article
  16. Article
  17. The Development of Epilepsy Following CNS Viral Infections: Mechanisms.Current neurology and neuroscience reports · 2024
    Review
  18. Upregulation of inflammatory genes and pathways links obesity to severe COVID-19.Biochimica et biophysica acta. Molecular basis of disease · 2024
    Article
  19. Article
  20. Review

4 more citing papers are in PubMed but not listed here.

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

14 authors at 3 institutions in 2 countries.

Frauke SeehusenLaboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
Jordan J ClarkDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK.ORCID 0000-0003-1790-7883
Parul SharmaDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK.
Eleanor G BentleyDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK.
Adam KirbyDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK.
Krishanthi SubramaniamDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK.
Sabina Wunderlin-GiulianiLaboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
Grant L HughesDepartments of Vector Biology and Tropical Disease Biology, Centre for Neglected Tropical Disease, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.ORCID 0000-0002-7567-7185
Edward I PattersonDepartments of Vector Biology and Tropical Disease Biology, Centre for Neglected Tropical Disease, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.ORCID 0000-0003-3465-0848
Benedict D MichaelDepartment of Clinical Infection Microbiology and Immunology and NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool L69 7BE, UK.ORCID 0000-0002-8693-8926
Andrew OwenDepartment of Pharmacology and Therapeutics, Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L3 3NY, UK.ORCID 0000-0002-9819-7651
Julian A HiscoxDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK.
James P StewartDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK.ORCID 0000-0002-8928-2037
Anja KiparLaboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.ORCID 0000-0001-7289-3459
University of Liverpool · GBLiverpool School of Tropical Medicine · GBUniversity of Zurich · CH

Funding

FDA HHS 75F40120C00085Medical Research Council MR/T028750/1Medical Research Council MR/V007181//1Medical Research Council MR/V007181/1Medical Research Council MR/V03605X/1Medical Research Council MR/W005611/1Wellcome Trust ISSF201902/3
6 · The paper itself

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2), we investigated the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with SARS-CoV-2 variants, as well as after prior influenza A virus infection. Apart from Omicron, we found all variants to frequently spread to and within the CNS. Infection was restricted to neurons and appeared to spread from the olfactory bulb mainly in basally oriented regions in the brain and into the spinal cord, independent of ACE2 expression and without evidence of neuronal cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed, accompanied by apoptotic death of endothelial, microglial and immune cells, without their apparent infection. Microgliosis and immune cell apoptosis indicate a potential role of microglia for pathogenesis and viral effect in COVID-19 and the possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates and broadly support the investigation of agents with adequate penetration into relevant regions of the CNS.

Indexed as

Angiotensin-Converting Enzyme 2Central Nervous SystemCOVID-19Viral TropismAnimalsHumansMiceMice, TransgenicPost-Acute COVID-19 SyndromeSARS-CoV-2ACE2 protein, humanAngiotensin-Converting Enzyme 2COVID-19encephalitisinfluenza A virus coinfectionmicrogliosismouse modelSevere Acute Respiratory Syndrome Coronavirus 2virus variants

Identifiers

PMID35632761
PMCPMC9146514
OpenAlexW4280585653

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.