Covid-19 and Gender: Lower Rate but Same Mortality of Severe Disease in Women

An Observational Study

Federico Raimondi; Luca Novelli; Arianna Ghirardi; Filippo Maria Russo; Dario Pellegrini; Roberta Biza; Roberta Trapasso; Lisa Giuliani; Marisa Anelli; Mariangela Amoroso; Chiara Allegri; Gianluca Imeri; Claudia Sanfilippo; Sofia Comandini; England Hila; Leonardo Manesso; Lucia Gandini; Pietro Mandelli; Martina Monti; Mauro Gori; Michele Senni; Ferdinando Luca Lorini; Marco Rizzi; Tiziano Barbuil Laura Paris; Alessandro Rambaldi; Roberto Cosentini; Giulio Guagliumi; Simonetta Cesa; Michele Colledan; Maria Sessa; Arianna Masciulli; Antonello Gavazzi; Sabrina Buoro; Giuseppe Remuzzi; Piero Ruggenenti; Annapaola Callegaro; Andrea Gianatti; Claudio Farina; Antonio Bellasi; Sandro Sironi; Stefano Fagiuoli; Fabiano Di Marco


BMC Pulm Med. 2021;21(96) 

In This Article


This retrospective, observational study was approved by the local Ethics Committee (Comitato Etico di Bergamo, Italy. N°37/2020). In the light of the urgent need to treat critical patients, and to avoid paper contamination, verbal consent was obtained when feasible, according to local protocol.

Source of Data

We collected data from electronic medical records of all adult patients with laboratory-confirmed SARS-CoV-2 infection, consecutively hospitalized for clinical reasons (i.e. respiratory failure in almost all cases) at Papa Giovanni XXIII Hospital (a tertiary hospital of 1080 beds), and its affiliate hospital, San Giovanni Bianco (a community hospital of 130 beds), between February 23rd and March 14th, 2020. Follow-up stopped on April 11th, 2020, to allow the observation for a minimum of 28 days in all patients since hospitalization. We did not include patients under eighteen year-old or patients already hospitalized for other conditions. Covid-19 has been diagnosed on the basis of the updated WHO interim guidance.[17] Medical history, demographic data, underlying comorbidities, viral exposure, clinical symptoms and/or signs, radiological and laboratory findings upon admission were derived from medical records, whereas information about family unit, healthcare job, pre-hospital medical contact, use of antibiotics and flu vaccine status were self-reported by the patient or relatives. Immunosuppression was defined as iatrogenic when due to chemotherapy, or treatment for solid organ transplantation or autoimmune diseases, otherwise it was HIV-related (Human Immunodeficiency Virus). Radiologic assessments and all laboratory tests were performed according to local clinical practice and based on clinical needs. At presentation, patients underwent routine blood tests, arterial blood gas analysis (ABG), and chest X-ray.

Laboratory Confirmation of SARS-CoV-2 Infection

SARS-CoV-2 genome from nasal swabs and respiratory samples was detected by two different molecular methods (GeneFinder COVID-19-Elitech Group, Allplex™ 2019—nCoV Assay—Seegene Inc) in line with the manufacturer's instructions. After the purification of viral RNA from clinical samples, the detection of RdRp, E and N viral genes was obtained by real time Polymerase Chain Reaction (RT-PCR) according to WHO protocol.[18]


The aim of this study was to describe gender differences in terms of clinical features and 28-day outcomes since hospitalization. The primary endpoint was 28-day all-cause mortality, occurring either during in-hospital stay or after discharge. The secondary endpoint was the development of severe disease, a composite outcome defined as the occurrence of at least one of the following: intensive or respiratory sub-intensive care unit admission; need of endotracheal intubation (ETI) and invasive ventilation, non-invasive ventilation (NIV), or continuous positive airway pressure (CPAP); death during hospitalization or after discharge.

Statistical Analysis

Descriptive statistics were used to summarize the baseline characteristics of Covid-19 patients. Continuous variables were expressed as mean ± standard deviation (SD) or as median and interquartile range [IQR], depending on their parametric or non-parametric distribution. Categorical variables were expressed as absolute counts and percentages. The chi-square test (or Fisher's exact test when appropriate) was used to test between group differences for the categorical variables, whereas the t-test or the Wilcoxon–Mann–Whitney test (for normally and not normally distributed variables, respectively) were used to compare continuous variables. Survival curve (overall and stratified by the need of CPAP/NIV at entry), according to gender was reported, with comparison by the log-rank test. Univariate logistic regression model was run to investigate predictors of 28-day mortality. A backward stepwise procedure was used to determine the best predictors of mortality to be included in the multivariable model. Results are presented as odds ratio (OR) with 95% confidence intervals (CI). Candidate predictors included in the stepwise procedure were variables that were available in at least 65% of patients and significantly different between patients who died and those who did not at a p value level of 0.05. The final multivariable model included predictors selected from the stepwise procedure along with some few other variables selected on biological plausibility and clinical judgment. To overcome the constraint of biased/overestimated results that may arise as a result of missing data, multiple imputation by chained equation (MICE), with 20 imputation sets, was used to impute the missing covariates involved in the final multivariable model. For all tested hypotheses, a two-tailed p values < 0.05 was considered significant. Analyses were performed using STATA software, release 16 (StataCorp LP, College Station, TX, USA).