Evidence map›Paper›PMID 34756178›Full record

Trial reportThe Lancet. Respiratory medicine2021

Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial.

Jozefien Declercq, Karel F A Van Damme, Elisabeth De Leeuw, Bastiaan Maes, Cedric Bosteels, Simon J Tavernier, Stefanie De Buyser, Roos Colman, Maya Hites, Gil Verschelden and 33 more

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Respiratory medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 13 pooled it
9.4field-weighted citation impact, top 2% 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

84 citing papers in PubMed, 13 syntheses or guidelines pooled it, 162 citations in OpenAlex.

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  9. Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2023
    Pooled it
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  12. Interleukin-1 blocking agents for treating COVID-19.The Cochrane database of systematic reviews · 2022
    Pooled it
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  18. Early administration of tocilizumab in hospitalized COVID-19 patients with elevated inflammatory markers; COVIDSTORM-a prospective, randomized, single-centre, open-label study.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2022
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24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors at 18 institutions in 1 country.

Jozefien DeclercqLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium.
Karel F A Van DammeLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium.
Elisabeth De LeeuwLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium.
Bastiaan MaesLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium.
Cedric BosteelsLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium.
Simon J TavernierLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Primary Immunodeficiency Research Laboratory, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Stefanie De BuyserBiostatistics Unit, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Roos ColmanBiostatistics Unit, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Maya HitesClinic of Infectious Diseases, Cliniques Universitaires de Bruxelles, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
Gil VerscheldenClinic of Infectious Diseases, Cliniques Universitaires de Bruxelles, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
Tom FivezIntensive Care Unit, ZOL Genk General Hospital, Genk, Belgium.
Filip MoermanDepartment of Infectious Diseases, CHR de La Citadelle General Hospital, Liège, Belgium.
Ingel K DemedtsDepartment of Pulmonary Medicine, AZ Delta General Hospital, Roeselare, Belgium.
Nicolas DaubyInstitute for Medical Immunology, Université Libre de Bruxelles and CHU Saint-Pierre University Hospital, Brussels, Belgium.
Nicolas De SchryverIntensive Care Unit, Clinique Saint-Pierre, Ottignies, Belgium.
Elke GovaertsDepartment of Pulmonary Medicine, AZ Sint-Lucas General Hospital, Ghent, Belgium.
Stefaan J VandecasteeleDepartment of Infectious Diseases, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium.
Johan Van LaethemDepartment of Internal Medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium.
Sebastien AnguilleDepartment of Hematology, University Hospital Antwerp, Antwerp, Belgium.
Jeroen van der HilstDepartment of Infectious Diseases and Immune Pathology, Jessa General Hospital and Limburg Clinical Research Center, Hasselt University, Hasselt, Belgium.
Benoit MissetDepartment of Intensive Care Medicine, University Hospital, Liège, Belgium.
Hans SlabbynckDepartment of Pulmonary Medicine, ZNA General Hospital, Antwerp, Belgium.
Xavier WitteboleIntensive Care Unit, Saint Luc University Hospital, UC Louvain, Brussels, Belgium.
Fabienne LiénartDepartment of Internal Medicine, CHU Tivoli University Hospital, La Louvière, Belgium.
Catherine LegrandInstitute of Statistics, Biostatistics and Actuarial Sciences (ISBA), Louvain Institute for Data Analysis and Modeling, Louvain-la-Neuve, Belgium.
Marc Buyse(22)IDDI, Louvain-la-Neuve, and Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt, Belgium.
Dieter StevensDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium.
Fre BautersDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium.
Leen J M SeysLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Helena AegerterLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Ursula SmoleLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Victor BosteelsDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Laboratory of ER Stress and Inflammation, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium.
Levi HosteDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Primary Immunodeficiency Research Laboratory, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Leslie NaesensDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Primary Immunodeficiency Research Laboratory, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Filomeen HaerynckDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Primary Immunodeficiency Research Laboratory, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Linos VandekerckhoveDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Infectious Diseases, University Hospital Ghent, Ghent, Belgium.
Pieter DepuydtDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Intensive Care Unit, University Hospital Ghent, Ghent, Belgium.
Eva van BraeckelDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium.
Sylvie RotteyDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Drug Research Unit, Ghent University, Ghent, Belgium.
Isabelle PeeneDepartment of Rheumatology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium.
Catherine Van Der StraetenHealth Innovation Research, University Hospital Ghent, Ghent, Belgium.
Frank HulstaertBelgian Health Care Knowledge Centre, Brussels, Belgium.
Bart N LambrechtLaboratory of Mucosal Immunology, VIB-UGhent Center for Inflammation Research, Ghent University, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium. Electronic address: bart.lambrecht@ugent.be.
AZ Sint-Jan · BEGhent University · BEUniversité Libre de Bruxelles · BEAntwerp University Hospital · BEAZ Delta · BEAZ Sint-Lucas · BEBelgian Health Care Knowledge Centre · BECentre hospitalier régional de la Citadelle · BECentre Hospitalier Universitaire de Saint-Pierre · BECentre Hospitalier Universitaire de Tivoli · BEClinique Saint Pierre · BECliniques Universitaires Saint-Luc · BEGhent University Hospital · BEHasselt University · BEUCLouvain · BEUniversitair Ziekenhuis Brussel · BEZiekenhuisnetwerk Antwerpen Stuivenberg · BEZiekenhuis Oost-Limburg · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInfections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome.

methodsWe did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO

findingsBetween April 4, and Dec 6, 2020, 342 patients were randomly assigned to IL-1 blockade (n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0·94 [95% CI 0·73-1·21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1·00 [0·78-1·29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups.

interpretationDrugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk.

fundingBelgian Health Care Knowledge Center and VIB Grand Challenges program.

Indexed as

COVID-19 Drug TreatmentCytokine Release SyndromeRespiratory InsufficiencyAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBelgiumFemaleFerritinsHumansHypoxiaInterleukin-1Interleukin-6 InhibitorsMaleMiddle AgedOxygenAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedFerritinsInterleukin-1Interleukin-6 InhibitorsOxygensiltuximabtocilizumab

Identifiers

PMID34756178
PMCPMC8555973
OpenAlexW3209567513

What OpenQuestion holds

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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.