Evidence map›Paper›PMID 36682515›Full record

ArticleBrain, behavior, and immunity2023

Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease.

Michelle A Erickson, Aric F Logsdon, Elizabeth M Rhea, Kim M Hansen, Sarah J Holden, William A Banks, Jessica L Smith, Cody German, Susan A Farr, John E Morley and 7 more

Open access · greenAbstract read
In one paragraph

Article in Brain, behavior, and immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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.

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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. A survey of SARS-CoV-2 tropism.Infectious diseases & immunity · 2025
    Review
  8. Review
  9. Neuroimmune pathophysiology of long COVID.Psychiatry and clinical neurosciences · 2025
    Review
  10. iPSC-derived human cortical organoids display profound alterations of cellular homeostasis following SARS-CoV-2 infection and Spike protein exposure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  11. Article
  12. Article
  13. The neurobiology of SARS-CoV-2 infection.Nature reviews. Neuroscience · 2024
    Review
  14. DoFrontiers in neuroscience · 2023
    Article
  15. Review
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

17 authors at 6 institutions in 2 countries.

Michelle A EricksonGeriatrics Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Aric F LogsdonGeriatrics Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Elizabeth M RheaGeriatrics Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Kim M HansenGeriatrics Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
Sarah J HoldenDepartment of Behavioral Neurosciences, Oregon Health and Science University, Portland, OR, USA.
William A BanksGeriatrics Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA. Electronic address: wabanks1@uw.edu.
Jessica L SmithThe Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Beaverton, OR, USA; Division of Pathobiology and Immunology Oregon National Primate Research Center, Oregon Health and Sciences University, Beaverton, OR, USA.
Cody GermanThe Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Beaverton, OR, USA; Division of Pathobiology and Immunology Oregon National Primate Research Center, Oregon Health and Sciences University, Beaverton, OR, USA.
Susan A FarrSaint Louis Veterans Affairs Medical Center, Research Service, St. Louis, MO, USA; Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.
John E MorleyDivision of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.
Riley R WeaverGeriatrics Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
Alec J HirschThe Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Beaverton, OR, USA; Division of Pathobiology and Immunology Oregon National Primate Research Center, Oregon Health and Sciences University, Beaverton, OR, USA.
Andrej KovacInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Eva KontsekovaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Kristen K BaumannGeriatrics Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
Mohamed A OmerGeriatrics Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
Jacob RaberDepartment of Behavioral Neurosciences, Oregon Health and Science University, Portland, OR, USA; Department of Neurology, Psychiatry, and Radiation Medicine, Division of Neuroscience, Departments of Neurology and Radiation Medicine, Oregon National Primate Research Center, Oregon Health Sciences University, Portland, OR, USA.
University of Puget Sound · USOregon National Primate Research Center · USSlovak Academy of Sciences · SKOregon Health & Science University · USSaint Louis University · USSt. Louis VA Medical Center · US

Funding

University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI SUMAN JAYADEV · 2020 to 2026
$29.0M
Effects of apoE Isoform, Sex and Diet on Insulin Regulation in BrainRF1AG059088 · NIA · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI BANKS, WILLIAM A, RABER, JACOB · 2018 to 2020
$2.5M
Role of human apolipoprotein E isoforms in long-term effects of West Nile Virus exposure on Alzheimer's disease-related behavioral alteration, cognitive injury, neuroinflammation, and neuropathologyR21AG079158 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI HIRSCH, ALEC J, RABER, JACOB · 2023 to 2024
$424k
Characterization of a human in vitro blood-brain barrier model to study the effects of systemic aging on responses to Alzheimer's disease effectorsR21AG065928 · NIA · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI ERICKSON, MICHELLE A. · 2020 to 2020
$374k
NIA NIH HHS P30 AG066509NIA NIH HHS R21 AG065928NIA NIH HHS RF1 AG059088
6 · The paper itself

Abstract

COVID-19 and especially Long COVID are associated with severe CNS symptoms and may place persons at risk to develop long-term cognitive impairments. Here, we show that two non-infective models of SARS-CoV-2 can cross the blood-brain barrier (BBB) and induce neuroinflammation, a major mechanism underpinning CNS and cognitive impairments, even in the absence of productive infection. The viral models cross the BBB by the mechanism of adsorptive transcytosis with the sugar N-acetylglucosamine being key. The delta and omicron variants cross the BB B faster than the other variants of concern, with peripheral tissue uptake rates also differing for the variants. Neuroinflammation induced by icv injection of S1 protein was greatly enhanced in young and especially in aged SAMP8 mice, a model of Alzheimer's disease, whereas sex and obesity had little effect.

Indexed as

Alzheimer DiseaseCOVID-19AnimalsBlood-Brain BarrierHumansMiceNeuroinflammatory DiseasesPost-Acute COVID-19 SyndromeSARS-CoV-2AgingAlzheimer's diseaseBlood–brain barrierCOVID-19GlycoproteinMicrogliaNeuroinflammationObesitySARS-CoV-2Virus

Identifiers

PMID36682515
PMCPMC9867649
OpenAlexW4317626592

What OpenQuestion holds

Textmetadata
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.