Evidence map›Paper›PMID 36494335›Full record

ArticleNature communications2022

SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling.

Scott B Biering, Francielle Tramontini Gomes de Sousa, Laurentia V Tjang, Felix Pahmeier, Chi Zhu, Richard Ruan, Sophie F Blanc, Trishna S Patel, Caroline M Worthington, Dustin R Glasner and 19 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
7.0field-weighted citation impact, top 2% 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

54 citing papers in PubMed, 74 citations in OpenAlex.

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  13. Dengue Virus NS1 Binds Ephrin B1 to Trigger Endothelial Dysfunction.bioRxiv : the preprint server for biology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 8 institutions in 1 country.

Scott B Biering *Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. sbiering@berkeley.edu.ORCID http://orcid.org/0000-0003-1991-629X
Francielle Tramontini Gomes de Sousa *Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Laurentia V TjangDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-0949-3713
Felix PahmeierDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-7445-2259
Chi ZhuDepartment of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA, USA.
Richard RuanDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Sophie F BlancDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-9550-1590
Trishna S PatelDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Caroline M WorthingtonChan Zuckerberg Biohub, San Francisco, CA, USA.
Dustin R GlasnerDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Bryan Castillo-RojasDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Venice ServellitaDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Nicholas T N LoDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-4289-1222
Marcus P WongDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Colin M WarnesDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-3088-8429
Daniel R SandovalDepartment of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA.
Thomas Mandel ClausenDepartment of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA.
Yale A SantosDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Douglas M FoxDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-9260-4079
Victoria OrtegaDepartment of Microbiology and Immunology, Cornell University, Ithaca, NY, USA.
Anders M NäärDepartment of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-7569-0291
Ralph S BaricDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-6827-8701
Sarah A StanleyDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Hector C AguilarDepartment of Microbiology and Immunology, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-6879-8360
Jeffrey D EskoDepartment of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA.
Charles Y ChiuInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-2915-2094
John E PakChan Zuckerberg Biohub, San Francisco, CA, USA.
P Robert BeattyDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Eva HarrisDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. eharris@berkeley.edu.ORCID http://orcid.org/0000-0002-7238-4037
University of California, Berkeley · USUniversity of California, San Francisco · USUniversity of California San Diego · USBerkeley Public Health Division · USChan Zuckerberg Initiative (United States) · USCornell University · USInnovative Genomics Institute · USUniversity of North Carolina at Chapel Hill · US

Funding

Protein Glycosylation in the Coagulopathy and Inflammation of SepsisP01HL131474 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MARTH, JAMEY · 2016 to 2025
$26.2M
EXPERIMENTAL ENDOCRINOLOGY AND METABOLISMT32DK007044 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Amit Majithia · 1986 to 2026
$4.6M
Mechanisms of Nipah virus fusion and entryR01AI109022 · NIAID · WASHINGTON STATE UNIVERSITY · PI AGUILAR-CARRENO, HECTOR · 2014 to 2024
$4.3M
Host factors and viral determinants mediating flavivirus NS1 tissue-specific endothelial dysfunction and vascular leakR01AI168003 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI Eva Harris · 2022 to 2026
$3.2M
Evaluation of in vitro and in vivo efficacy of glycan-based compounds against flavivirus endothelial permeability and vascular leakR21AI146464 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI HARRIS, EVA · 2020 to 2021
$886k
NHLBI NIH HHS P01 HL131474NIAID NIH HHS R01 AI109022NIAID NIH HHS R01 AI168003NIAID NIH HHS R21 AI146464NIDDK NIH HHS T32 DK007044
6 · The paper itself

Abstract

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the triggers of vascular leak are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to induce barrier dysfunction in vitro and vascular leak in vivo, independently of viral replication and the ACE2 receptor. We identify an S-triggered transcriptional response associated with extracellular matrix reorganization and TGF-β signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-β signaling axis are required for S-mediated barrier dysfunction. Notably, we show that SARS-CoV-2 infection caused leak in vivo, which was reduced by inhibiting integrins. Our findings offer mechanistic insight into SARS-CoV-2-triggered vascular leak, providing a starting point for development of therapies targeting COVID-19.

Indexed as

COVID-19SARS-CoV-2Angiotensin-Converting Enzyme 2Endothelial CellsHumansIntegrinsPeptidyl-Dipeptidase ASpike Glycoprotein, CoronavirusTransforming Growth Factor betaAngiotensin-Converting Enzyme 2IntegrinsPeptidyl-Dipeptidase ASpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Transforming Growth Factor beta

Identifiers

PMID36494335
PMCPMC9734751
OpenAlexW4312019859

What Socratic holds

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LicenceCC BY
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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.