Sex-related differences in lung injury distribution and outcomes in COVID-19 acute respiratory failure: insights from the CT-COVID19 multicenter study group
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background 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. Methods 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. Results 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 2 /FiO 2 (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). Conclusions 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.
Authors: 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, Pietro Bonaffini, Matteo Cazzaniga, Ferdinando Luca Lorini, Irene Ottaviani, Asia Borgo, Mario Tavola, Livio Ferraris, Giacomo Bellani, Stefano Gatti, Davide Ippolito, Andrea Restivo, Filippo Serra, Massimo Arlotti, Marino Gatti, Beatrice Tamagnini, Enrico Cavagna, Emiliano Gamberini, Davide De Ponti, Giuseppe Galbiati, Matteo Giacomini
Institutions: Azienda Socio Sanitaria Territoriale Bergamo Est, Azienda Ospedaliera San Gerardo, University of Milano-Bicocca, Harvard University, Massachusetts General Hospital, University of Pennsylvania, University of Iowa, University of Milan, Ospedale Infermi di Rimini, Azienda Unità Sanitaria Locale Rimini, ASST Melegnano e della Martesana, University of Ferrara, Arcispedale Sant'Anna, Ospedale Papa Giovanni XXIII, Center for Astrophysics Harvard & Smithsonian, Ollscoil na Gaillimhe – University of Galway, University Hospital Galway
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,890
OpenAlex ID: W7164919284