Evidence map›Paper›PMID 38838150›Full record

ArticleScience advances2024

Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2.

Mohammed R Shaker, Andrii Slonchak, Bahaa Al-Mhanawi, Sean D Morrison, Julian D J Sng, Justin Cooper-White, Alexander A Khromykh, Ernst J Wolvetang

Abstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
–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

27 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Relative biological effectiveness and neural stem cell fate in carbon ion-irradiated human brain organoids.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. A survey of SARS-CoV-2 tropism.Infectious diseases & immunity · 2025
    Review
  18. Article
  19. Article
  20. 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

8 authors.

Mohammed R ShakerAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.ORCID 0000-0002-3675-4598
Andrii SlonchakSchool of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.ORCID 0000-0003-3258-0508
Bahaa Al-MhanawiAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.ORCID 0000-0002-7425-3364
Sean D MorrisonAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.ORCID 0000-0001-9128-8713
Julian D J SngSchool of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.ORCID 0000-0001-7837-4473
Justin Cooper-WhiteAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.ORCID 0000-0002-1920-8229
Alexander A KhromykhSchool of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.
Ernst J WolvetangAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.ORCID 0000-0002-2146-6614

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Why individuals with Down syndrome (DS) are more susceptible to SARS-CoV-2-induced neuropathology remains elusive. Choroid plexus (ChP) plays critical roles in barrier function and immune response modulation and expresses the ACE2 receptor and the chromosome 21-encoded TMPRSS2 protease, suggesting its substantial role in establishing SARS-CoV-2 infection in the brain. To explore this, we established brain organoids from DS and isogenic euploid iPSC that consist of a core of functional cortical neurons surrounded by a functional ChP-like epithelium (ChPCOs). DS-ChPCOs recapitulated abnormal DS cortical development and revealed defects in ciliogenesis and epithelial cell polarity in ChP-like epithelium. We then demonstrated that the ChP-like epithelium facilitates infection and replication of SARS-CoV-2 in cortical neurons and that this is increased in DS. Inhibiting TMPRSS2 and furin activity reduced viral replication in DS-ChPCOs to euploid levels. This model enables dissection of the role of ChP in neurotropic virus infection and euploid forebrain development and permits screening of therapeutics for SARS-CoV-2-induced neuropathogenesis.

Indexed as

BrainChoroid PlexusCOVID-19Down SyndromeOrganoidsSARS-CoV-2Serine EndopeptidasesAngiotensin-Converting Enzyme 2FurinHumansInduced Pluripotent Stem CellsNeuronsViral TropismVirus ReplicationACE2 protein, humanAngiotensin-Converting Enzyme 2FurinSerine EndopeptidasesTMPRSS2 protein, human

Identifiers

PMID38838150
PMCPMC11152128

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.