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Background <p>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.</p> Methods <p>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.</p> Results <p>Among 850 patients (35% women), men exhibited larger lung volume (2.91 vs. 2.28 L, <i>p</i> &lt; 0.001), greater lung mass (1.14 vs. 0.93&#xa0;kg, <i>p</i> &lt; 0.001), and higher SP (5.79 vs. 5.21 cmH₂O, <i>p</i> &lt; 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; <i>p</i> &lt; 0.001), lower PaO<sub>2</sub>/FiO<sub>2</sub> (OR 0.99, 95% CI 0.98–0.99; <i>p</i> &lt; 0.001), higher SOFA score (OR 2.67, 95% CI 1.43–4.98; <i>p</i> = 0.002 for SOFA ≥ 2), higher global SP (OR 1.18, 95% CI 1.05–1.34; <i>p</i> = 0.005), and male sex (OR 1.76, 95% CI 1.06–2.92; <i>p</i> = 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).</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月16日

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  • 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

摘要

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 PaO2/FiO2 (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.