Evidence map›Paper›PMID 38376212›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2024

Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.

Neil R Aggarwal, Jacquie Nordwall, Dominique L Braun, Lucy Chung, Jordan Coslet, Tatyana Der, Nnakelu Eriobu, Adit A Ginde, Awori J Hayanga, Helene Highbarger and 21 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Trial
  2. Article
  3. Observational
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors.

Neil R AggarwalDivision of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0000-0002-0922-8824
Jacquie NordwallDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
Dominique L BraunDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Lucy ChungCAMRIS International (under contract no. 75N93019D00025 with National Institute of Allergy and Infectious Diseases, Department of Health and Human Services), National Institute of Health, Bethesda, Maryland, USA.
Jordan CosletVelocity Clinical Research, Chula Vista, California, USA.
Tatyana DerDepartment of General Internal Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Nnakelu EriobuInstitute of Human Virology Nigeria, Abuja, Nigeria.
Adit A GindeDepartment of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Awori J HayangaDepartment of Cardiovascular Thoracic Surgery, West Virginia University School of Medicine, Morgantown, West Virginia, USA.
Helene HighbargerVirus Isolation and Serology Laboratory, Frederick National Laboratory, National Cancer Institute, Frederick, Maryland, USA.
Mark HolodniyVeterans Affairs Palo Alto Health Care System, Division of Infectious Diseases and Geographic Medicine, Stanford University, Palo Alto, California, USA.
Juan P HorcajadaDepartment of Infectious Diseases, Hospital del Mar Research Insititute, UPF, Barcelona, Spain.
Mamta K JainDivision of Infectious Diseases and Geotropical Medicine, UT Southwestern Medical Center and Parkland Health and Hospital System, Dallas, Texas, USA.
Kami KimDivision of Infectious Disease and International Medicine, Morsani College of Medicine, University of South Florida and Global Emerging Diseases Institute, Tampa General Hospital, Tampa, Florida, USA.
Sylvain LaverdureLaboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, National Cancer Institute, Frederick, Maryland, USA.
Jens LundgrenCHIP Center of Excellence for Health, Immunity, and Infections and Department of Infectious Diseases, Righospitalet, University of Copenhagen, Copenhagen, Denmark.
Ven NatarajanLaboratory of Molecular Cell Biology, Frederick National Laboratory, National Cancer Institute, Frederick, Maryland, USA.
Hien H NguyenDivision of Infectious Diseases, Veterans Affairs Northern California, University of California, Davis, Sacramento, California, USA.
Sarah L PettThe Medical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, United Kingdom.
Andrew PhillipsInstitute for Global Health, University College London, London, United Kingdom.
Garyphallia PoulakouThird Department of Medicine and Laboratory National and Kapodistrian University of Athens Medical School, Athens, Greece.
David A PriceNewcastle Upon Tyne NHUS Hospitals Foundation Trust, Newcastle Upon Tyne, United Kingdom.
Philip RobinsonInfection Prevention and Hospital Epidemiology, Hoag Memorial Hospital Presbyterian, Newport Beach, California, USA.
Angela J RogersDivision of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Palo Alto, California, USA.
Uriel SandkovskyDivision of Infectious Diseases, Baylor University Medical Center, Dallas, Texas, USA.
Katy Shaw-SalibaNational Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, Maryland, USA.
Jeffrey M SturekDivision of Pulmonary and Critical Care Medicine, Department of Medicine, UVA Health, Charlottesville, Virginia, USA.
Barbara W TrautnerMichael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA.
Michael WatersVelocity Clinical Research, Chula Vista, California, USA.
Cavan ReillyDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
ACTIV-3/TICO Study Group

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI PENDLETON, RICHARD · 2019 to 2025
$3932.6M
ACTIV Integration of Host-targeting Therapies for COVID-19 Administrative Coordinating CenterOT2HL156812 · NHLBI · RESEARCH TRIANGLE INSTITUTE · PI NOLEN, TRACY L, THOMAS, SONIA M · 2020 to 2024
$1270.7M
REVISED CAROL ACT IIU01HL088942 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GELIJNS, ANNE CHRISTINE, MOSKOWITZ, ALAN J · 2007 to 2025
$122.6M
Extended follow-up of randomized participants in the INSIGHT START trialU01AI136780 · NIAID · UNIVERSITY OF MINNESOTA · PI GRUND, BIRGIT, REILLY, CAVAN S. · 2019 to 2024
$18.0M
Network for Cardiothoracic Surgical Investigations in Cardiovascular MedicineUM1HL088925 · NHLBI · UNIVERSITY OF VIRGINIA · PI BADHWAR, VINAY, KRON, IRVING L. · 2013 to 2025
$6.8M
National Institute of Allergy and Infectious DiseasesNCI NIH HHS 75N91019D00024NHLBI NIH HHS OT2 HL156812NHLBI NIH HHS U01 HL088942NHLBI NIH HHS UM1 HL088925NIAID NIH HHS U01 AI136780NIH HHS 75N91019D00024NIH HHS U01-AI136780University of Minnesota
6 · The paper itself

Abstract

backgroundPersistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials.

methodsA secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models.

resultsViral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06-3.22]; ≥4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time.

conclusionsBaseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.

Indexed as

Antiviral AgentsCOVID-19HospitalizationInterleukin-6SARS-CoV-2AdultAgedAntibodies, ViralAntigens, ViralCOVID-19 Drug TreatmentFemaleHumansMaleMiddle AgedRNA, ViralAntibodies, ViralAntigens, ViralAntiviral AgentsInterleukin-6RNA, Viralacute COVID-19host responseviral factors

Identifiers

PMID38376212
PMCPMC11175705

What OpenQuestion holds

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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.