Evidence map›Paper›PMID 34235728›Full record

ArticleBritish journal of pharmacology2022

Advocacy of targeting protease-activated receptors in severe coronavirus disease 2019.

Saravanan Subramaniam, Wolfram Ruf, Markus Bosmann

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 20% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    Article
  8. Review
  9. Review
  10. Article
  11. Editorial: COVID-19 and thrombo-inflammatory responses.Frontiers in cardiovascular medicine · 2023
    Article
  12. Article
  13. Article
  14. Review
  15. 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

3 authors at 2 institutions in 2 countries.

Saravanan SubramaniamPulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
Wolfram RufCenter for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Markus BosmannPulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
Boston University · USScripps Research Institute · US

Funding

Project-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3M
Analysis and Characterization of Trauma-Induced CoagulopathyUM1HL120877 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI MORRISSEY, JAMES H., WISNIEWSKI, STEPHEN R · 2013 to 2019
$26.6M
Role reversal of MAVS in bacterial sepsisR01HL141513 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BOSMANN, MARKUS · 2018 to 2022
$2.4M
Bacterial polyphosphates in sepsisR01AI153613 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BOSMANN, MARKUS · 2021 to 2024
$2.1M
New genetic models for C5a receptorsR01HL139641 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BOSMANN, MARKUS · 2018 to 2022
$2.1M
NCATS NIH HHS UL1 TR001430NHLBI NIH HHS R01 HL139641NHLBI NIH HHS R01 HL141513NHLBI NIH HHS UM1 HL120877NIAID NIH HHS R01 AI153613
6 · The paper itself

Abstract

Identifying drug targets mitigating vascular dysfunction, thrombo-inflammation and thromboembolic complications in COVID-19 is essential. COVID-19 coagulopathy differs from sepsis coagulopathy. Factors that drive severe lung pathology and coagulation abnormalities in COVID-19 are not understood. Protein-protein interaction studies indicate that the tagged viral bait protein ORF9c directly interacts with PAR2, which modulates host cell IFN and inflammatory cytokines. In addition to direct interaction of SARS-CoV-2 viral protein with PARs, we speculate that activation of PAR by proteases plays a role in COVID-19-induced hyperinflammation. In COVID-19-associated coagulopathy elevated levels of activated coagulation proteases may cleave PARs in association with TMPRSS2. PARs activation enhances the release of cytokines, chemokines and tissue factor expression to propagate IFN-dependent inflammation, leukocyte-endothelial interaction, vascular permeability and coagulation responses. This hypothesis, corroborated by in vitro findings and emerging clinical evidence, will focus targeted studies of PAR1/2 blockers as adjuvant drugs against cytokine release syndrome and COVID-19-associated coagulopathy. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc.

Indexed as

COVID-19 Drug TreatmentCytokine Release SyndromeHumansInflammationReceptors, Proteinase-ActivatedSARS-CoV-2Receptors, Proteinase-Activatedacute respiratory distress syndromeCOVID-19-associated coagulopathyPAR1PAR2sepsis

Identifiers

PMID34235728
PMCPMC8794588
OpenAlexW3178175522

What OpenQuestion holds

Textmetadata
LicenceTDM
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.