Evidence map›Paper›PMID 39884670›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2025

The circulating renin-angiotensin system and mortality among patients hospitalized for COVID-19: a mechanistic substudy of the ACTIV-4 Host Tissue trials.

Christopher L Schaich, Mark C Chappell, Matthew S Shotwell, Meghan M Joly, Kevin W Gibbs, Aaron Barksdale, Ivor S Douglas, Peter Chen, Joseph E Levitt, Michael A Puskarich and 9 more

Abstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Renin-angiotensin-aldosterone system inhibitors - why they won't help in COVID-19.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Article
  2. 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

19 authors.

Christopher L SchaichDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States.ORCID 0000-0002-5302-0828
Mark C ChappellDepartment of Surgery, Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States.ORCID 0000-0001-5869-6037
Matthew S ShotwellDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Meghan M JolyVanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Kevin W GibbsDepartment of Internal Medicine, Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States.ORCID 0000-0002-5272-2289
Aaron BarksdaleDepartment of Emergency Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States.
Ivor S DouglasDepartment of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, Denver Health Medical Center, Anschutz School of Medicine, University of Colorado, Denver, Colorado, United States.ORCID 0000-0002-4541-1431
Peter ChenDepartment of Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States.ORCID 0000-0002-5330-1718
Joseph E LevittDepartment of Medicine, Stanford University, Stanford, California, United States.
Michael A PuskarichDepartment of Emergency Medicine, Hennepin Healthcare, Minneapolis, Minnesota, United States.
Todd W RiceDepartment of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt Institute for Clinical Trials Research, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Michelle S HarkinsDepartment of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, United States.ORCID 0000-0002-9679-2553
Kristin M HudockDepartment of Medicine, University of Cincinnati, Cincinnati, Ohio, United States.
Michael J LanspaDepartment of Pulmonary/Critical Care Medicine, Intermountain Medical Center, Murray, Utah, United States.
Adit A GindeDepartment of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States.
Wesley H SelfVanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Sean P CollinsDepartment of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
D Clark FilesDepartment of Internal Medicine, Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States.
ACTIV-4 Host Tissue Investigators

Funding

Uric Acid, Klotho and Salt Sensitivity in Young Adults Born PretermR01HL146818 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI CHAPPELL, MARK C, SHALTOUT, HOSSAM · 2019 to 2023
$4.0M
Cardiac Autonomic Function, Cognitive Performance, and Neurocognitive OutcomesK01AG073581 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SCHAICH, CHRISTOPHER · 2021 to 2024
$384k
HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) 1OT2HL156812HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL146818HHS | NIH | National Institute on Aging (NIA) K01AG073581NHLBI NIH HHS R01 HL146818NIA NIH HHS K01 AG073581Vanderbilt University Medical Center (VUMC) VUMC92086
6 · The paper itself

Abstract

SARS-CoV-2 targets angiotensin-converting enzyme-2 (ACE2), a key peptidase of the renin-angiotensin system (RAS), which regulates the balance of the vasoconstrictor/inflammatory peptide Ang II and the vasodilator/anti-inflammatory peptide Ang-(1-7). Few studies have quantified the circulating elements of the RAS longitudinally in SARS-CoV-2 infection and their association with COVID-19 outcomes. Thus, we evaluated the association of circulating RAS enzymes and peptides with mortality among patients with COVID-19. Blood samples were collected from 111 patients with COVID-19 and new-onset hypoxemia during the delta and omicron waves at 19 hospitals in the United States. Circulating RAS components were quantified via radioimmunoassay or ELISA at 0 (baseline), 1, 3, and 5 days after randomization. We used multivariable Cox regression to estimate the association of baseline and longitudinal RAS concentrations with 90-day mortality. Participants were aged 18-90 (means [SD]: 55 [14]) yr and 62% were male. There were 22 (20%) deaths over 90 days of follow-up. ACE2 levels above the sample median (≥4.9 pM; adjusted HR [95% CI]: 0.10 [0.02, 0.43]) and ACE2/ACE ratio (≥6.0 × 10

Indexed as

COVID-19Renin-Angiotensin SystemAdolescentAdultAgedAged, 80 and overAngiotensin-Converting Enzyme 2Angiotensin IFemaleHospitalizationHumansMaleMiddle AgedPeptide FragmentsSARS-CoV-2Young AdultACE2 protein, humanAngiotensin-Converting Enzyme 2Angiotensin Iangiotensin I (1-7)Peptide FragmentsCOVID-19critical carehypoxemiapulmonaryrenin-angiotensin system

Identifiers

PMID39884670
PMCPMC12101116

What OpenQuestion holds

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LicenceCC BY-NC
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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.