Evidence map›Paper›PMID 34759819›Full record

ArticleFrontiers in pharmacology2021

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip.

Amir Bein, Seongmin Kim, Girija Goyal, Wuji Cao, Cicely Fadel, Arash Naziripour, Sanjay Sharma, Ben Swenor, Nina LoGrande, Atiq Nurani and 13 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Gastrointestinal tract, its pathophysiology andWorld journal of gastroenterology · 2025
    Review
  9. Review
  10. Host-microbe-cancer interactions on-a-chip.Frontiers in bioengineering and biotechnology · 2025
    Review
  11. Review
  12. Intestinal organ chips for disease modelling and personalized medicine.Nature reviews. Gastroenterology & hepatology · 2024
    Review
  13. Review
  14. Review
  15. Review
  16. Frontiers in immunology · 2024
    Review
  17. Organ-on-chip technology: Opportunities and challenges.Biotechnology notes (Amsterdam, Netherlands) · 2024
    Review
  18. Review
  19. Review
  20. Recent Advances in Cell-Based In Vitro Models to Recreate Human Intestinal Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    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

23 authors at 5 institutions in 1 country.

Amir BeinWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Seongmin KimWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Girija GoyalWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Wuji CaoWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Cicely FadelWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Arash NaziripourWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Sanjay SharmaWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Ben SwenorWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Nina LoGrandeWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Atiq NuraniWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Vincent N MiaoProgram in Health Sciences & Technology, Harvard Medical School & MIT, Cambridge, MA, United States.
Andrew W NaviaInstitute for Medical Engineering and Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Cambridge, MA, United States.
Carly G K ZieglerProgram in Health Sciences & Technology, Harvard Medical School & MIT, Cambridge, MA, United States.
José Ordovas MontañesBroad Institute of MIT and Harvard, Cambridge, MA, United States.
Pranav PrabhalaWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Min Sun KimWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Rachelle Prantil-BaunWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Melissa RodasWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Amanda JiangWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Lucy O'SullivanWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Gladness TillyaWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Alex K ShalekProgram in Health Sciences & Technology, Harvard Medical School & MIT, Cambridge, MA, United States.
Donald E IngberWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States.
Harvard University · USBoston Children's Hospital · USBroad Institute · USHarvard–MIT Division of Health Sciences and Technology · USRagon Institute of MGH, MIT and Harvard · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
NIDDK NIH HHS P30 DK034854NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313
6 · The paper itself

Abstract

Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PBMCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.

Indexed as

coronavirusCOVID-19intestine chipnafamostatNL63organs on chipremdesevirSARS–CoV–2

Identifiers

PMID34759819
PMCPMC8573067
OpenAlexW3209898855

What OpenQuestion 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 OpenQuestion graph.