Sex-related differences in lung injury distribution and outcomes in COVID-19 acute respiratory failure: insights from the CT-COVID19 multicenter study group

Davide Signori; Alice Nova; Yi Xin; Sarah E Gerard; Aurora Magliocca; Giovanni Vitale; Linda Mussoni; Jonathan Montomoli; Matteo Subert; Alessandra Ponti; Savino Spadaro; Giancarla Poli; Francesco Casola; Roberta Garberi; Andrea Restivo; Davide Raimondi Cominesi; Marco Giani; Vanessa Zambelli; Giuseppe Foti; John G Laffey; Maurizio Cereda; Emanuele Rezoagli; CT-COVID19 Multicenter Study Group

doi:10.1186/s40635-026-00914-4

Back

Sex-related differences in lung injury distribution and outcomes in COVID-19 acute respiratory failure: insights from the CT-COVID19 multicenter study group

Journal article

Open access

Peer reviewed

Sex-related differences in lung injury distribution and outcomes in COVID-19 acute respiratory failure: insights from the CT-COVID19 multicenter study group

Davide Signori, Alice Nova, Yi Xin, Sarah E Gerard, Aurora Magliocca, Giovanni Vitale, Linda Mussoni, Jonathan Montomoli, Matteo Subert, Alessandra Ponti, …

Intensive care medicine experimental, Vol.14(1), 76

06/16/2026

DOI: 10.1186/s40635-026-00914-4

PMCID: PMC13272716

PMID: 42301582

Files and links (1)

url

https://doi.org/10.1186/s40635-026-00914-4View

Published (Version of record) Open Access

Abstract

Sex-related differences have been consistently reported in the epidemiology of acute hypoxemic respiratory failure (AHRF) and COVID-19. However, whether computed tomography (CT)-derived measures of lung injury differ between sexes and contribute to outcome disparities remains unclear. In this large multicenter retrospective cohort study, we analyzed 850 spontaneously breathing patients with COVID-19-related AHRF who underwent early chest CT at hospital admission. Quantitative CT analysis provided measures of lung density, volume, mass, and superimposed pressure (SP), a CT-derived estimate of gravitational stress. Sex-stratified analyses compared morphological, physiological, and outcome variables. Multivariable logistic regression models identified independent predictors of mortality. Among 850 patients (35% women), men exhibited larger lung volume (2.91 vs. 2.28 L, p < 0.001), greater lung mass (1.14 vs. 0.93 kg, p < 0.001), and higher SP (5.79 vs. 5.21 cmH₂O, p < 0.001) despite similar fractions of ground-glass opacities and consolidation. In the multivariable model, older age (OR 1.08, 95% CI 1.06-1.11; p < 0.001), lower PaO /FiO (OR 0.99, 95% CI 0.98-0.99; p < 0.001), higher SOFA score (OR 2.67, 95% CI 1.43-4.98; p = 0.002 for SOFA ≥ 2), higher global SP (OR 1.18, 95% CI 1.05-1.34; p = 0.005), and male sex (OR 1.76, 95% CI 1.06-2.92; p = 0.028) were independently associated with an increased risk of mortality. In the mediation analysis, the effect of global SP on mortality does not appear to be mediated by male sex (coefficient 0.00). Male patients with COVID-19-related AHRF exhibited higher global SP than females, reflecting greater gravitational lung load and mechanical disadvantage. Both global SP and male sex were independently associated with mortality, with no evidence of mediation of male sex on mortality. These finding suggest that, beyond anatomical and mechanical differences, biological and hormonal factors likely contribute to the increased disease severity observed in men.

Computed Tomography

COVID-19

Sex differences

Superimposed pressure

Acute hypoxemic respiratory failure

Mortality

Details

Title: Subtitle: Sex-related differences in lung injury distribution and outcomes in COVID-19 acute respiratory failure: insights from the CT-COVID19 multicenter study group
Creators: Davide Signori - Azienda Socio Sanitaria Territoriale Lariana
Alice Nova - Azienda Ospedaliera San Gerardo
Yi Xin - Massachusetts General Hospital
Sarah E Gerard - University of Iowa
Aurora Magliocca - IRCCS Policlinico San Donato
Giovanni Vitale - IRCCS Policlinico San Donato
Linda Mussoni - Istituto per la Ricerca Sociale
Jonathan Montomoli - Ospedale Infermi di Rimini
Matteo Subert - ASST Melegnano e della Martesana
Alessandra Ponti - IRCCS Policlinico San Donato
Savino Spadaro - University of Ferrara
Giancarla Poli - Ospedale Papa Giovanni XXIII
Francesco Casola - Harvard University
Roberta Garberi - Azienda Ospedaliera San Gerardo
Andrea Restivo - Azienda Ospedaliera San Gerardo
Davide Raimondi Cominesi - Department of Emergency and Intensive Care, Fondazione IRCCS San Gerardo Dei Tintori Hospital, Monza, Italy
Marco Giani - University of Milano-Bicocca
Vanessa Zambelli - University of Milano-Bicocca
Giuseppe Foti - University of Milano-Bicocca
John G Laffey - Ollscoil na Gaillimhe – University of Galway
Maurizio Cereda - Massachusetts General Hospital
Emanuele Rezoagli - Azienda Ospedaliera San Gerardo
CT-COVID19 Multicenter Study Group
Resource Type: Journal article
Publication Details: Intensive care medicine experimental, Vol.14(1), 76
DOI: 10.1186/s40635-026-00914-4
PMID: 42301582
PMCID: PMC13272716
NLM abbreviation: Intensive Care Med Exp
ISSN: 2197-425X
eISSN: 2197-425X
Publisher: Springer Nature
Grant note: Bicocca Starting grant 2020 from the University of Milano-Bicocca with the project titled: "Functional Residual Capacity Assessment using a Wash-In/Wash-Out technique based on a fast main-stream O2 Sensor with nanofluorescenT geometry for severe lung injury (FAST)- COVID / Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca beyond" / Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca
Language: English
Date published: 06/16/2026
Academic Unit: Roy J. Carver Department of Biomedical Engineering
Record Identifier: 9985175371902771

Metrics

1 Record Views