Evidence map›Paper›PMID 41088445›Full record

ArticleCritical care (London, England)2025

Circulating endothelial signatures correlate with worse outcomes in COVID-19, respiratory failure and ARDS.

Ana C Costa Monteiro, Harry Pickering, Aartik Sarma, Clove S Taylor, Meagan M Jenkins, Fei-Man Hsu, Brian Nadel, Ofer Levy, Lindsey R Baden, Esther Melamed and 47 more

2 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Critical care (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Not yet cited in PubMed.

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

NCT01892969 completednot on this map

Coagulation and Fibrinolysis in a Pediatric Insulin Titration Trial

TypeobservationalSponsorUniversity of California, San FranciscoRan2012 to 2016Enrolled304ConditionsHeart Failure, Respiratory Failure
NCT04378777 completednot on this map

A Prospective Cohort Study to Assess Longitudinal Immune Responses in Hospitalized Patients With COVID-19 (DAIT-COVID-19-002)

TypeobservationalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2020 to 2022Enrolled1,227ConditionsCoronavirus Disease 2019 (COVID-19), SARS-CoV-2ArmsBiological sample collection, Data Collection: Clinical Care Assessments
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

57 authors.

Ana C Costa MonteiroUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA. Acostamonteiro@mednet.ucla.edu.
Harry PickeringUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA.
Aartik SarmaUniversity of California- San Francisco, San Francisco, CA, USA.
Clove S TaylorUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA.
Meagan M JenkinsUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA.
Fei-Man HsuUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA.
Brian NadelUniversity of Southern California, Los Angeles, CA, USA.
Ofer LevyDepartment of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Lindsey R BadenHarvard Medical School, Boston, MA, USA.
Esther MelamedUniversity of Texas- Austin, Austin, TX, USA.
Lauren I R EhrlichUniversity of Texas- Austin, Austin, TX, USA.
Grace A McComseyCase Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA.
Rafick P SekalyEmory University, Atlanta, GA, USA.
Charles B CairnsDrexel University College of Medicine, Philadelphia, PA, USA.
Elias K HaddadDrexel University College of Medicine, Philadelphia, PA, USA.
Albert C ShawYale University School of Medicine, New Haven, CT, USA.
David A HaflerYale University School of Medicine, New Haven, CT, USA.
Ruth R MontgomeryYale University School of Medicine, New Haven, CT, USA.
David B CorryBaylor School of Medicine, Houston, TX, USA.
Farrah KheradmandBaylor School of Medicine, Houston, TX, USA.
Mark A AtkinsonUniversity of Florida College of Medicine, Gainesville, FL, USA.
Scott C BrakenridgeUniversity of Washington School of Medicine, Seattle, WA, USA.
Nelson I Agudelo HiguitaOklahoma University Health Sciences Center, Oklahoma City, OK, USA.
Jordan P MetcalfOklahoma University Health Sciences Center, Oklahoma City, OK, USA.
Catherine L HoughOregon Health & Science University, Portland, OR, USA.
William B MesserOregon Health & Science University, Portland, OR, USA.
Bali PulendranStanford University School of Medicine, Stanford, CA, USA.
Kari C NadeauHarvard T. H. Chan School of Public Health, Boston, MA, USA.
Mark M DavisStanford University School of Medicine, Stanford, CA, USA.
Linda N GengStanford University School of Medicine, Stanford, CA, USA.
Ana Fernandez-SesmaIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Viviana SimonIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Florian KrammerIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Monica KraftIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Chris BimeUniversity of Arizona College of Medicine, Phoenix, AZ, USA.
Carolyn S CalfeeUniversity of California- San Francisco, San Francisco, CA, USA.
David J ErleUniversity of California- San Francisco, San Francisco, CA, USA.
Steve BosingerEmory University, Atlanta, GA, USA.
Walter EckalbarUniversity of California- San Francisco, San Francisco, CA, USA.
Holden MaeckerStanford University School of Medicine, Stanford, CA, USA.
Adeeb RahmanImmunai, New York, NY, USA.
Leying GuanYale University School of Medicine, New Haven, CT, USA.
Bjoern PetersLa Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Steven H KleinsteinYale University School of Medicine, New Haven, CT, USA.
Alison D AugustineNational Institute of Allergy and Infectious Disease, Bethesda, USA.
Joann Diray-ArceHarvard Medical School, Boston, MA, USA.
Patrice M BeckerNational Institute of Allergy and Infectious Disease, Bethesda, USA.
Nadine RouphaelEmory University, Atlanta, GA, USA.
IMPACC Network
CAFPINT Site investigators of the PALISI Network
Michael AgusDepartment of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Hrishikesh KulkarniUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA.
Joanna M SchaenmannUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA.
Ramin Salehi-RadUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA.
Michael A MatthayUniversity of California- San Francisco, San Francisco, CA, USA.
Elaine F ReedUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA.
Anil SapruUniversity of California School of Medicine- Los Angeles, Los Angeles, CA, USA. ASapru@mednet.ucla.edu.

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Translation of immunologic technologies from basic research into pre-clinical nonU19AI062629 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI THOMPSON, LINDA F · 2004 to 2023
$56.2M
Systems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI David A. Hafler, RUTH R MONTGOMERY · 2010 to 2026
$50.4M
Project 3 - Ex vivo immune profiling of dengue viruses and vaccinesU19AI118610 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KASARSKIS, ANDREW · 2015 to 2021
$46.6M
Systems Biological Analysis of Innate and Adaptive Responses to VaccinationU19AI090023 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, LI, SHUZHAO · 2010 to 2021
$45.0M
Understanding Asthma EndotypesU19AI077439 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI David J Erle · 2008 to 2026
$41.1M
Clinical and Translational Science Collaborative of Northern Ohio, Catalyzing Linkages to Equity in Health (CLE Health)UM1TR004528 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI GRACE A MCCOMSEY · 2023 to 2026
$32.1M
Transcriptomics to define biomarkers of neonatal vaccine immunogenicityU19AI118608 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI OZONOFF, AL · 2017 to 2021
$24.7M
Tollip inhibits IL-33 signaling during airway influenza virus infectionU19AI125357 · NIAID · UNIVERSITY OF ARIZONA · PI KRAFT, MONICA · 2016 to 2025
$14.7M
Systems Immunology profiling of respiratory viral infections in vulnerable populationsU19AI167891 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI Matthew C. Altman, Carmen R Mikacenic · 2022 to 2026
$14.0M
Systems biological assessment of T cell responses to vaccinationU19AI167903 · NIAID · STANFORD UNIVERSITY · PI BALI PULENDRAN · 2022 to 2026
$13.2M
BLRD VA IK2 BX006194NCATS NIH HHS UM1 TR004528NHLBI NIH HHS K23 HL165149NHLBI NIH HHS K23HL165149NHLBI NIH HHS R01 HL114484NHLBI NIH HHS R01 HL166449NHLBI NIH HHS R01-HL166449, R01-HL169860NHLBI NIH HHS R01 HL169860NHLBI NIH HHS R01 HL170601NHLBI NIH HHS R01HL170601NHLBI NIH HHS U01 HL107681NHLBI NIH HHS U01HL107681NIAID NIH HHS R01 AI104870NIAID NIH HHS R01 AI132774NIAID NIH HHS R01 AI135803NIAID NIH HHS R01 AI145835NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI062629NIAID NIH HHS U19 AI077439NIAID NIH HHS U19 AI089992NIAID NIH HHS U19 AI090023NIAID NIH HHS U19 AI118608NIAID NIH HHS U19 AI118610NIAID NIH HHS U19 AI125357NIAID NIH HHS U19 AI128910NIAID NIH HHS U19 AI128913NIAID NIH HHS U19 AI167891NIAID NIH HHS U19 AI167903NIAID NIH HHS U54 AI142766NIH HHS P51 OD011132NIH HHS R01AI104870NIH HHS R01AI132774NIH HHS R01AI135803NIH HHS R01AI145835NIH HHS R01HL114484NIH HHS S10 OD026799NIH HHS U19AI057229NIH HHS U19AI062629NIH HHS U19AI077439NIH HHS U19AI089992NIH HHS U19AI090023NIH HHS U19AI118608NIH HHS U19AI118610NIH HHS U19AI125357NIH HHS U19AI128910NIH HHS U19AI128913NIH HHS U24AI52179NIH HHS U54AI142766
6 · The paper itself

Abstract

backgroundElevated circulating endothelial cells (CECs), released from monolayers after insult, have been implicated in worse outcomes in ARDS and COVID-19, however there is no consensus proteomic phenotype that define CECs. We queried whether a transcriptomic approach would alternatively support the presence of endothelial cells in circulation and correlate with worsening respiratory failure.

methodsTo test whether elevated endothelial cell signatures (ECS) in circulation plays a role in worse respiratory outcomes, we used unsupervised bulk-transcriptome deconvolution to quantify ECS% in two cohorts. Our pilot analysis included pediatric patients requiring invasive mechanical ventilation (CAF-PINT, NCT01892969). Our validation cohort included adult hospitalized patients with COVID-19 (IMPACC, NCT04378777), testing the association of ECS% to outcomes in patients at risk of acute respiratory failure/ARDS. Primary outcome was 28-day mortality.

resultsIn CAF-PINT, day 0 ECS% was higher in non-survivors compared to survivors of respiratory failure (2.8%, IQR 2.4-3.4% versus 2.6%, IQR 2.2-3.0% n = 244, p < 0.05, Wilcoxon rank-sum). In IMPACC, baseline ECS% (< 72 h of hospitalization) was higher in COVID-19 non-survivors versus survivors (2.9%, IQR 2.6-3.4%, versus 2.7%, IQR 2.3-3.1%, n = 932, p < 0.001, Wilcoxon rank-sum). Each 1% increase in baseline ECS% was significantly associated with mortality (adjusted OR 1.36, CI 1.03-1.79) by multivariable logistic regression. Increased baseline ECS% was associated with worse respiratory trajectories (2.5%, IQR 2.2-2.8% for trajectory with no oxygen requirements, 2.9%, IQR 2.6-3.4% for the trajectory with fatal outcome by day 28, n = 932, p < 0.001, one-way ANOVA).

conclusionQuantifying ECS by deconvolution supports a transcriptomics-driven approach towards the non-invasive evaluation of endothelial damage in respiratory outcomes. This is a first step towards elucidating mechanistic components linking endothelial damage to ARDS utilizing non-invasive, circulating transcriptomic data by leveraging a novel deconvolution approach.

Indexed as

COVID-19Endothelial CellsRespiratory Distress SyndromeRespiratory InsufficiencyAdultAgedChildCohort StudiesFemaleHumansMaleMiddle AgedPilot Projects

Identifiers

PMID41088445
PMCPMC12522733

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Registered trials

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.