Evidence map›Paper›PMID 33908688›Full record

ArticleEMBO reports2021

Rapid endotheliitis and vascular damage characterize SARS-CoV-2 infection in a human lung-on-chip model.

Vivek V Thacker, Kunal Sharma, Neeraj Dhar, Gian-Filippo Mancini, Jessica Sordet-Dessimoz, John D McKinney

Open access · bronzeAbstract read
In one paragraph

Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
6.4field-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

82 citing papers in PubMed, 133 citations in OpenAlex.

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22 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

6 authors at 1 institution in 1 country.

Vivek V ThackerGlobal Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.ORCID 0000-0002-1681-627X
Kunal SharmaGlobal Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.ORCID 0000-0001-8086-3436
Neeraj DharGlobal Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.ORCID 0000-0002-5887-8137
Gian-Filippo ManciniHistology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Jessica Sordet-DessimozHistology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.ORCID 0000-0003-2982-3273
John D McKinneyGlobal Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.ORCID 0000-0002-0557-3479
École Polytechnique Fédérale de Lausanne · CH

Funding

Novartis Foundation for Medical-Biological Research (#20C240)Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF) 310030B_176397
6 · The paper itself

Abstract

Severe cases of SARS-CoV-2 infection are characterized by hypercoagulopathies and systemic endotheliitis of the lung microvasculature. The dynamics of vascular damage, and whether it is a direct consequence of endothelial infection or an indirect consequence of an immune cell-mediated cytokine storm remain unknown. Using a vascularized lung-on-chip model, we find that infection of alveolar epithelial cells leads to limited apical release of virions, consistent with reports of monoculture infection. However, viral RNA and proteins are rapidly detected in underlying endothelial cells, which are themselves refractory to apical infection in monocultures. Although endothelial infection is unproductive, it leads to the formation of cell clusters with low CD31 expression, a progressive loss of barrier integrity and a pro-coagulatory microenvironment. Viral RNA persists in individual cells generating an inflammatory response, which is transient in epithelial cells but persistent in endothelial cells and typified by IL-6 secretion even in the absence of immune cells. Inhibition of IL-6 signalling with tocilizumab reduces but does not prevent loss of barrier integrity. SARS-CoV-2-mediated endothelial cell damage thus occurs independently of cytokine storm.

Indexed as

COVID-19SARS-CoV-2Cytokine Release SyndromeEndothelial CellsHumansLungalveolar modelsCOVID-19interleukin-6organ-on-chipvasculitis

Identifiers

PMID33908688
PMCPMC8183417
OpenAlexW3159931117

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.