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

Costa Monteiro, AC; Pickering, H; Sarma, A; Taylor, CS; Jenkins, MM; Hsu, FM; Nadel, B; Levy, O; Baden, LR; Melamed, E; Ehrlich, LIR; McComsey, GA; Sekaly, RP; Cairns, CB; Haddad, EK; Shaw, AC; Hafler, DA; Montgomery, RR; Corry, DB; Kheradmand, F; Atkinson, MA; Brakenridge, SC; Higuita, NIA; Metcalf, JP; Hough, CL; Messer, WB; Pulendran, B; Nadeau, KC; Davis, MM; Geng, LN; Fernandez-Sesma, A; Simon, V; Krammer, F; Kraft, M; Bime, C; Calfee, CS; Erle, DJ; Bosinger, S; Eckalbar, W; Maecker, H; Rahman, A; Guan, L; Peters, B; Kleinstein, SH; Augustine, AD; Diray-Arce, J; Becker, PM; Rouphael, N; IMPACC Network; CAFPINT Site investigators of the PALISI Network; Agus, M; Kulkarni, H; Schaenmann, JM; Salehi-Rad, R; Matthay, MA; Reed, EF; Sapru, A

doi:10.1186/s13054-025-05596-0

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

Crit CarePublished 14 Oct 2025Retrospective cohort study

Main finding · Baseline ECS% (< 72 h of hospitalization), IMPACC validation cohortResultAdjusted odds ratio 1.36 CI 1.03–1.79

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Authors' conclusion

Quantifying ECS by deconvolution supports a transcriptomics-driven approach towards the non-invasive evaluation of endothelial damage in respiratory outcomes.

Study context

Population: Pediatric patients requiring invasive mechanical ventilation (CAF-PINT, pilot) and adult hospitalized patients with COVID-19 at risk of acute respiratory failure/ARDS (IMPACC, validation)two cohorts

Exposure: Circulating endothelial cell signatures in non-survivors vs survivors
Outcome: 28-day mortality
Follow-up: 28 days

Methodological detailsunsupervised bulk-transcriptome deconvolution, pilot and validation cohorts

Unsupervised bulk-transcriptome deconvolution
Pilot and validation cohorts

Main finding

As reported in the abstract

Baseline ECS% (< 72 h of hospitalization), IMPACC validation cohort

Adjusted odds ratio

1.36

CI 1.03–1.79

By group

Non-survivors2.9%IQR 2.6–3.4%

Survivors2.7%IQR 2.3–3.1%

Each 1% increase in baseline ECS%

aOR 1.36 (CI 1.03–1.79)

Each 1% increase in baseline ECS%, as printed

Observational data: associations, not effects.

Further findings

Outcome	Non-survivors	Survivors	P value
Day 0 ECS%, CAF-PINT pilot cohort (pediatric respiratory failure)Wilcoxon rank-sum; n = 244	2.8% (IQR 2.4–3.4%)	2.6% (IQR 2.2–3.0%)	P < 0.05
Baseline ECS% by respiratory trajectory, IMPACCFatal outcome by day 28 trajectory vs No oxygen requirements trajectory · one-way ANOVA; n = 932			P < 0.001

Baseline endothelial cell signatures (ECS)% by respiratory trajectory, IMPACC: No oxygen requirements trajectory 2.5% (IQR 2.2–2.8%)
Baseline ECS% by respiratory trajectory, IMPACC: Fatal outcome by day 28 trajectory 2.9% (IQR 2.6–3.4%)

Baseline ECS% by respiratory trajectory, IMPACC

Increased baseline ECS% associated with worse respiratory trajectories

Reference

Authors: Costa Monteiro AC, Pickering H, Sarma A, Taylor CS, Jenkins MM, Hsu FM, et al.
All 57 authors
Costa Monteiro AC, Pickering H, Sarma A, Taylor CS, Jenkins MM, Hsu FM, Nadel B, Levy O, Baden LR, Melamed E, Ehrlich LIR, McComsey GA, Sekaly RP, Cairns CB, Haddad EK, Shaw AC, Hafler DA, Montgomery RR, Corry DB, Kheradmand F, Atkinson MA, Brakenridge SC, Higuita NIA, Metcalf JP, Hough CL, Messer WB, Pulendran B, Nadeau KC, Davis MM, Geng LN, Fernandez-Sesma A, Simon V, Krammer F, Kraft M, Bime C, Calfee CS, Erle DJ, Bosinger S, Eckalbar W, Maecker H, Rahman A, Guan L, Peters B, Kleinstein SH, Augustine AD, Diray-Arce J, Becker PM, Rouphael N, IMPACC Network, CAFPINT Site investigators of the PALISI Network, Agus M, Kulkarni H, Schaenmann JM, Salehi-Rad R, Matthay MA, Reed EF, Sapru A
Journal: Critical Care
Published: 14 Oct 2025
DOI: 10.1186/s13054-025-05596-0
PubMed: 41088445
Registration: NCT01892969; NCT04378777

Topic: Respiratory failure & ventilation

Exposure

Circulating endothelial cell signatures (ECS%) in non-survivors vs survivors

Key notes

Non-survivors vs Survivors: P < 0.001
Mortality; multivariable logistic regression

Original publication

Circulating endothelial signatures correlate with worse outcomes in COVID-19, respiratory failure and ARDS. Crit Care. Published 14 October 2025. doi:10.1186/s13054-025-05596-0

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