Evidence mapPaperPMID 40100623Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Deficiency in platelet 12-lipoxygenase exacerbates inflammation and disease severity during SARS-CoV-2 infection.

Ana Claudia Dos S P Andrade, Emile Lacasse, Isabelle Dubuc, Leslie Gudimard, Annie Gravel, Florian Puhm, Gabriel Campolina-Silva, Celso Queiroz-Junior, Isabelle Allaeys, Julien Prunier and 7 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Deficiency in platelet 12-lipoxygenase exacerbates inflammation and disease severity during SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2025
    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

17 authors.

Ana Claudia Dos S P AndradeDivision of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.
Emile LacasseDivision of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.
Isabelle DubucDivision of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.
Leslie GudimardDivision of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.
Annie GravelDivision of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.ORCID 0000-0001-5229-5750
Florian PuhmDivision of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.ORCID 0000-0001-5699-6626
Gabriel Campolina-SilvaDivision of Reproduction, mother and youth health, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.
Celso Queiroz-JuniorMorphology Department, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.
Isabelle AllaeysDivision of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.ORCID 0000-0003-4697-046X
Julien PrunierDivision of Endocrinology and Nephrology, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.
Oumaima Azeggouar WallenCentre de recherche de l'Institut Universitaire de cardiologie et pneumologie de Québec, Division of pneumology, Faculty of medicine, Université Laval, Québec City, QC G1V 4G5, Canada.ORCID 0009-0008-6377-6689
Élizabeth DumaisCentre de recherche de l'Institut Universitaire de cardiologie et pneumologie de Québec, Division of pneumology, Faculty of medicine, Université Laval, Québec City, QC G1V 4G5, Canada.
Clémence BelleannéeDivision of Reproduction, mother and youth health, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.
Arnaud DroitDivision of Endocrinology and Nephrology, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.
Nicolas FlamandCentre de recherche de l'Institut Universitaire de cardiologie et pneumologie de Québec, Division of pneumology, Faculty of medicine, Université Laval, Québec City, QC G1V 4G5, Canada.ORCID 0000-0001-5944-7200
Éric BoilardDivision of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.ORCID 0000-0001-6319-6432
Louis FlamandDivision of Infectious and Immune Diseases, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec City, QC G1V 4G2, Canada.ORCID 0000-0001-5010-4586

Funding

Canadian Government | Canadian Institutes of Health Research (CIHR) 172632Canadian Government | Canadian Institutes of Health Research (CIHR) GA1-117694
6 · The paper itself

Abstract

Platelets, known for maintaining blood balance, also participate in antimicrobial defense. Upon severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, platelets become hyperactivated, releasing molecules such as cytokines, granule contents, and bioactive lipids. The key effector biolipids produced by platelets include 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosatrienoic acid (12-HETrE), produced by 12-lipoxygenase (12-LOX), and prostaglandins and thromboxane, produced by cyclooxygenase-1. While prostaglandin E2 and thromboxane B2 were previously associated with lung inflammation in severe COVID-19, the role of platelet 12-LOX in SARS-CoV-2 infection remains unclear. Using mice deficient for platelets' 12-LOX, we report that SARS-CoV-2 infection resulted in higher lung inflammation characterized by histopathological tissue analysis, increased leukocyte infiltrates, and cytokine production relative to wild-type mice. In addition, distinct platelet and lung transcriptomic changes, including alterations in NOD-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) inflammasome-related gene expression, were observed. Mass spectrometry lipidomic analysis in 12-LOX-deficient-infected mice revealed significant changes in bioactive lipid content, including reduced levels of 12-HETrE that inversely correlated with disease severity. Finally, platelet 12-LOX deficiency was associated with increased morbidity and lower survival rates relative to wild type (WT) mice. Overall, this study highlights the complex interplay between 12-LOX-related lipid metabolism and inflammatory responses during SARS-CoV-2 infection. The findings provide valuable insights into potential therapeutic targets aimed at mitigating severe outcomes, emphasizing the pivotal role of platelet enzymes in the host response to viral infections.

Indexed as

Arachidonate 12-LipoxygenaseBlood PlateletsCOVID-19InflammationSARS-CoV-2AnimalsCytokinesHumansLungMiceMice, Inbred C57BLMice, KnockoutSeverity of Illness IndexArachidonate 12-LipoxygenaseCytokines12-HETrEInflammationplateletsplatelet type-12 lipoxygenaseSARS-CoV-2

Identifiers

PMID40100623
PMCPMC11962506

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.