Riassunto analitico
Background: Sex differences in prognosis of severe COVID19 disease and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference.
Methods: Retrospective, observational cohort study among patients with COVID-19 severe pneumonia. A survival analysis was conducted to compare the time to the composite endpoint of mechanical ventilation or death by sex. Interaction was formally tested to compare the risk difference by sex in subsets. Mediation analysis with a binary endpoint mechanical ventilation or death (yes/no) by end of follow-up for a number of inflammation and/or coagulation biomarkers in the context of counterfactual prediction was also conducted.
Results: Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years. At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PiO2/FiO2 (254 mmHg vs 191 mmHg; p=0.023). By 28 days from hospital admission 49.2% (95% CI: 39.6-58.9%) of males vs. 31.7% (17.9-45.4%) of females underwent mechanical ventilation or death (log-rank p-value<0.0001). This amounted to a difference in HR of 0.40 (0.26-0.63, p=0.0001). The AUC in CRP over the study period appeared to be explain 85% of this difference in risk by sex.
Conclusions: Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. CRP showed a predominant role to mediate the difference in risk by sex paving the way to future possible therapeutic strategies.
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Abstract
Background: Sex differences in prognosis of severe COVID19 disease and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference.
Methods: Retrospective, observational cohort study among patients with COVID-19 severe pneumonia. A survival analysis was conducted to compare the time to the composite endpoint of mechanical ventilation or death by sex. Interaction was formally tested to compare the risk difference by sex in subsets. Mediation analysis with a binary endpoint mechanical ventilation or death (yes/no) by end of follow-up for a number of inflammation and/or coagulation biomarkers in the context of counterfactual prediction was also conducted.
Results: Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years. At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PiO2/FiO2 (254 mmHg vs 191 mmHg; p=0.023). By 28 days from hospital admission 49.2% (95% CI: 39.6-58.9%) of males vs. 31.7% (17.9-45.4%) of females underwent mechanical ventilation or death (log-rank p-value<0.0001). This amounted to a difference in HR of 0.40 (0.26-0.63, p=0.0001). The AUC in CRP over the study period appeared to be explain 85% of this difference in risk by sex.
Conclusions: Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. CRP showed a predominant role to mediate the difference in risk by sex paving the way to future possible therapeutic strategies.
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