Evidence map›Paper›PMID 35837388›Full record

ArticleFrontiers in immunology2022

Mediators of Obesity Do Not Influence SARS-CoV-2 Infection or Activation of Primary Human Lung Microvascular Endothelial Cells

Bram M Ter Ellen, Jelmer Niewold, Antine Flikweert, Anneke C Muller Kobold, Peter Heeringa, Matijs van Meurs, Jolanda M Smit, Peter H J van der Voort, Izabela A Rodenhuis-Zybert, Jill Moser

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In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. 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

10 authors at 2 institutions in 1 country.

Bram M Ter EllenDepartment of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Jelmer NiewoldDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Antine FlikweertDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Anneke C Muller KoboldDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Peter HeeringaDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Matijs van MeursDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Jolanda M SmitDepartment of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Peter H J van der VoortDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Izabela A Rodenhuis-ZybertDepartment of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Jill MoserDepartment of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
University of Groningen · NLUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clinical observations have shown that obesity is associated with the severe outcome of SARS-CoV-2 infection hallmarked by microvascular dysfunction in the lungs and other organs. Excess visceral fat and high systemic levels of adipose tissue (AT) derived mediators such as leptin and other adipokines have also been linked to endothelial dysfunction. Consequently, we hypothesized that AT-derived mediators may exacerbate microvascular dysfunction during of SARS-CoV-2 infection and tested this in a primary human lung microvascular endothelial (HLMVEC) cell model. Our results indicate that HLMVEC are not susceptible to SARS-CoV-2 infection since no expression of viral proteins and no newly produced virus was detected. In addition, exposure to the virus did not induce endothelial activation as evidenced by a lack of adhesion molecule, E-selectin, VCAM-1, ICAM-1, and inflammatory cytokine IL-6 induction. Incubation of endothelial cells with the pro-inflammatory AT-derived mediator, leptin, prior to virus inoculation, did not alter the expression of endothelial SARS-CoV-2 entry receptors and did not alter their susceptibility to infection. Furthermore, it did not induce inflammatory activation of endothelial cells. To verify if the lack of activated phenotype in the presence of adipokines was not leptin-specific, we exposed endothelial cells to plasma obtained from critically ill obese COVID-19 patients. Plasma exposure did not result in E-selectin, VCAM-1, ICAM-1, or IL-6 induction. Together our results strongly suggest that aberrant inflammatory endothelial responses are not mounted by direct SARS-CoV-2 infection of endothelial cells, even in the presence of leptin and other mediators of obesity. Instead, endothelial activation associated with COVID-19 is likely a result of inflammatory responses initiated by other cells. Further studies are required to investigate the mechanisms regulating endothelial behavior in COVID-19 and the mechanisms driving severe disease in obese individuals.

Indexed as

COVID-19Endothelial CellsE-SelectinHumansIntercellular Adhesion Molecule-1Interleukin-6LungObesitySARS-CoV-2Vascular Cell Adhesion Molecule-1E-SelectinIntercellular Adhesion Molecule-1Interleukin-6Vascular Cell Adhesion Molecule-1adipokinesendothelial activationendothelial cellsinflammationleptinSARS-CoV-2

Identifiers

PMID35837388
PMCPMC9273911
OpenAlexW4283658049

What OpenQuestion holds

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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.