Evidence map›Paper›PMID 36301025›Full record

ArticleImmunity, inflammation and disease2022

Exploratory analysis of interleukin-38 in hospitalized COVID-19 patients.

Dennis M de Graaf, Lisa U Teufel, Aline H de Nooijer, Adriaan J van Gammeren, Antonius A M Ermens, Ildikó O Gaál, Tania O Crișan, Frank L van de Veerdonk, Mihai G Netea, Charles A Dinarello and 3 more

Open access · goldAbstract read
In one paragraph

Article in Immunity, inflammation and disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 55% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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

13 authors at 4 institutions in 4 countries.

Dennis M de GraafDepartment of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.ORCID 0000-0002-9198-7159
Lisa U TeufelDepartment of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Aline H de NooijerDepartment of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Adriaan J van GammerenDepartment of Clinical Chemistry and Hematology, Amphia Hospital, Breda, The Netherlands.
Antonius A M ErmensDepartment of Clinical Chemistry and Hematology, Amphia Hospital, Breda, The Netherlands.
Ildikó O GaálDepartment of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Tania O CrișanDepartment of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Frank L van de VeerdonkDepartment of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Mihai G NeteaDepartment of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Charles A DinarelloDepartment of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Leo A B JoostenDepartment of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Rob J W ArtsDepartment of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Radboudumc Center for Infectious Diseases COVID-19 Study Group
Radboud University Nijmegen · NLAmphia Ziekenhuis · NLIuliu Hațieganu University of Medicine and Pharmacy · ROUniversity of Bonn · DE

Funding

Yeast-based HTS Assay Technologies for ProteasesR01AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1985 to 2025
$8.5M
NIAID NIH HHS R01 AI015614
6 · The paper itself

Abstract

introductionA major contributor to coronavirus disease 2019 (COVID-19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin-38 (IL-38) is an IL-1 family member with broad anti-inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL-38 in COVID-19 patients in comparison to healthy controls, whereas two other studies report no differences in IL-38 concentrations.

methodsHere, we present an exploratory, retrospective cohort study of circulating IL-38 concentrations in hospitalized COVID-19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age- and sex-matched healthy subjects. Plasma IL-38 concentrations were measured by enzyme-linked immunosorbent assay, disease-related proteins by proximity extension assay, and clinical data were retrieved from hospital records.

resultsIL-38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL-38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL-38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL-38 and the inflammatory biomarker d-dimer was observed in men of the validation cohort. In women of the validation cohort, IL-38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL-38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL-10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein.

conclusionsThese data indicate that IL-38 is not associated with disease outcomes in hospitalized COVID-19 patients. However, moderate correlations between IL-38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL-38 concentrations are not indicative of COVID-19 severity, its anti-inflammatory effects may reduce COVID-19 severity and should be experimentally investigated.

Indexed as

COVID-19SerpinsAnti-Inflammatory AgentsBiomarkersFemaleHumansInterleukinsMaleRetrospective StudiesSARS-CoV-2Anti-Inflammatory AgentsBiomarkersIL-38 protein, humanInterleukinsSERPINA12 protein, humanSerpinsCOVID-19interleukin-38retrospective cohort studySARS-CoV-2

Identifiers

PMID36301025
PMCPMC9601778
OpenAlexW4307648853

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.