The hidden interplay between sex and COVID-19 mortality: the role of cardiovascular calcification

Alberto Cereda,Arif Khokhar,Giacomo Bellani,Francesco Giannini,Alessandra Scoccia,Valeria Nicoletti,Mario Iannaccone,Marco Loffi,Giuseppe Sangiorgi ,Matteo Bertini,Paolo Giacomo Vaudano,Aldo P Maggioni ,Gianmarco Iannopollo,Alberto Monello,Pietro Sergio,Antonio Colombo,Anna Palmisano,Gianluca Campo,Gianluigi Patelli,Davide Ippolito,Claudio Rapezzi,Luigi Vignali,Davide Vignale,Riccardo Leone,Chiara Gnasso,Daniele Andreini,Gianluca Pontone,Nicola Sverzellati,Antonio Mangieri,Tommaso Nannini,Gabriele Tumminello,Francesca Besana,Piergiorgio Turchio,Marco Toselli,Antonio Esposito

doi:10.1007/s11357-021-00409-y

Abstract

Recent clinical and demographical studies on COVID-19 patients have demonstrated that men experience worse outcomes than women. However, in most cases, the data were not stratified according to gender, limiting the understanding of the real impact of gender on outcomes. This study aimed to evaluate the disaggregated in-hospital outcomes and explore the possible interactions between gender and cardiovascular calcifications. Data was derived from the sCORE-COVID-19 registry, an Italian multicentre registry that enrolled COVID-19 patients who had undergone a chest computer tomography scan on admission. A total of 1683 hospitalized patients (mean age 67±14 years) were included. Men had a higher prevalence of cardiovascular comorbidities, a higher pneumonia extension, more coronary calcifications (63% vs.50.9%, p<0.001), and a higher coronary calcium score (391±847 vs. 171±479 mm3, p<0.001). Men experienced a significantly higher mortality rate (24.4% vs. 17%, p=0.001), but the death event tended to occur earlier in women (15±7 vs. 8±7 days, p= 0.07). Non-survivors had a higher coronary, thoracic aorta, and aortic valve calcium score. Female sex, a known independent predictor of a favorable outcome in SARS-CoV2 infection, was not protective in women with a coronary calcification volume greater than 100 mm3. There were significant differences in cardiovascular comorbidities and vascular calcifications between men and women with SARS-CoV2 pneumonia. The differences in outcomes can be at least partially explained by the different cardiovascular profiles. However, women with poor outcomes had the same coronary calcific burden as men. The presumed favorable female sex bias in COVID-19 must therefore be reviewed in the context of comorbidities, especially cardiovascular ones.

Highlights

The SARS-CoV2 outbreak has had a significant impact on healthcare services and resource allocation
The presumed favorable female sex bias in COVID-19 must be reviewed in the context of comorbidities, especially cardiovascular ones
The present study aims to describe gender differences in terms of clinical and radiological features and in-hospital outcomes of COVID-19 patients

Summary

Introduction

The SARS-CoV2 outbreak has had a significant impact on healthcare services and resource allocation. Accumulating evidence has shown that amongst COVID-19-infected patients, elevated mortality is observed in older patients and those with pre-existing comorbidities, including hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, and cancer [1,2,3]. The available sex-disaggregated data reveal that men experience a higher hospitalization rate, a more severe disease than women with a consequent higher overall case fatality ratio [1]. Epidemiological data on sex differences are still under investigation and need to be cleared of potential bias. A better knowledge of sex differences in incidence and mortality in the COVID-19 pandemic is the first step to analyze the biological patterns to define gender-specific prevention and treatment strategies. The high cardiovascular risk profile of males and females has been proposed to explain the observed gender bias in outcomes

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