Sex differences in clinical phenotype and transitions of care among individuals dying of COVID-19 in Italy
Authors: Raparelli Valeria , Palmieri Luigi , Canevelli Marco , Pricci Flavia , Unim Brigid , Lo Noce Cinzia , Villani Emanuele R. , Rochon Paula A. , Pilote Louise , Vanacore Nicola , Onder Graziano ,   Italian National Institute of Health COVID-19 Mortality Group, Palmieri Luigi , Agazio Elvira , Andrianou Xanthi , Barbariol Pierfrancesco , Bella Antonino , Bellino Stefania , Benelli Eva , Bertinato Luigi , Boros Stefano , Brambilla Gianfranco , Calcagnini Giovanni , Canevelli Marco , Castrucci Maria Rita , Censi Federica , Ciervo Alessandra , Colaizzo Elisa , D’Ancona Fortunato , Del Manso Martina , Donfrancesco Chiara , Fabiani Massimo , Facchiano Francesco , Filia Antonietta , Floridia Marco , Galati Fabio , Giuliano Marina , Grisetti Tiziana , Kodra Yllka , Langer Martin , Lega Ilaria , Lo Noce Cinzia , Maiozzi Pietro , Malchiodi Albedi Fiorella , Manno Valerio , Martini Margherita , Urdiales Alberto Mateo , Mattei Eugenio , Meduri Claudia , Meli Paola , Minelli Giada , Nebuloni Manuela , Nistico Lorenza , Nonis Marino , Onder Graziano , Palmisano Lucia , Petrosillo Nicola , Pezzotti Patrizio , Pricci Flavia , Punzo Ornella , Puro Vincenzo , Raparelli Valeria , Rezza Giovanni , Riccardo Flavia , Rota Maria Cristina , Salerno Paolo , Serra Debora , Siddu Andrea , Stefanelli Paola , Tamburo De Bella Manuela , Tiple Dorina , Unim Brigid , Vaianella Luana , Vanacore Nicola , Vichi Monica , Villani Emanuele Rocco , Zona Amerigo , Brusaferro Silvio 
Published: October 2020

Background

Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available.

Methods

A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27–June 11, 2020). Clinical characteristics and the times from symptoms’ onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex.

Results

Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39–2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29–2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13–1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55–0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25–0.63), yet both sexes had a high level of multimorbidity. The times from symptoms’ onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45–5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13–1.90).

Conclusions

Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.