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


In the first three weeks of the pandemic 431 adult Covid-19 patients were admitted by the ER to our hospital. Their demographic and clinical characteristics are reported in Table 1. 119 were female (27.6%), and the majority were Caucasian (98.6%). The mean (± SD) age was 67.6 ± 13.0 years, notably no significant differences were observed between female and male (67.0 ± 14.5 vs 67.8 ± 12.5 years, respectively, p = 0.54). Regardless of gender, most patients had documented relevant comorbidities, especially systemic hypertension (55.8%), and diabetes (19.8%). However, being a former smoker, a previous history of myocardial infarction or vasculopathy were significantly more common in males (33.3% vs 20.5%, 16.1% vs 3.4%, 15.4% vs 6.8%; p = 0.025, p < 0.001, p = 0.020; respectively). The comorbidity burden, as estimated by the Charlson Comorbidity Index (CCI), attained a median value of 4.0 [IQR 2.0–5.0] and was comparable between categories as well as medication history, immunosuppression and flu vaccine status.

Pre-hospital, Clinical and Laboratory Features at Presentation

Pre-hospital epidemiology, in terms of contact with healthcare facilities or infection occurrence within family unit, was homogeneous among groups (Table 2). Half of the patients had taken antibiotics before hospitalization and fever was the most frequent symptom at home (90.1%), followed by dyspnea (59.3%) and cough (50.2%). Interestingly, gastrointestinal symptoms (i.e. anorexia, nausea, vomiting, diarrhea) were significantly more prevalent in females (24.6% vs 15.7%; p = 0.033). Relevant intervals between symptoms onset and clinically important episodes are reported in Additional file 1: Table S1. The median interval between symptoms onset and ER admission resulted of 7.0 days [5.0–10.0], without significant difference according to gender (8.0 [5.0–10.5] vs 7.0 [5.0–10.0]) in females and males, respectively, p = 0.97). Of note, interval between hospitalization and CPAP/NIV treatment was significantly shorter in males (1 day [1–3] vs 2 days [1–4]; p = 0.017).

Characteristics at presentation to ER are shown in Table 3. Most of the patients were alert (93.8%), and febrile (65.2%), with normal blood pressure and normal heart rate. ABG showed for both sexes a tendency to respiratory alkalosis, with a median pH of 7.47 [7.44–7.50], median PaCO2 of 33 mmHg [IQR 30–35], and median HCO3 of 24.1 mmol/l [22.0–26.0]. Females showed a small but significant higher heart rate and HCO3 (Table 3). Also PaO2/FiO2 at admission, on average severely reduced, was not statistically different between male and female (229 mmHg [134–273] vs 238 mmHg [150–281], p = 0.28).

Laboratory and radiographic findings at admission are reported in Table 4. Liver transaminases, both AST and ALT, were higher in males than in females (53 U/L vs 40 U/L and 40 U/L vs 30 U/L, respectively; p < 0.001). Urea and creatinine values were normal, although significantly lower in female (0.74 mg/dL vs 0.98 mg/dL and 38 mg/dL vs 48 mg/dL, respectively; p < 0.001). CRP was generally elevated (113 [56–162] mg/L), with cases of very high levels (i.e. > 127 mg/L) being more common in males (35.4 vs 48.7%, p 0.015). Procalcitonin (PCT) levels were higher in males (0.56 ng/mL [IQR 0.21–2.35] vs 0.12 ng/mL [IQR 0.05–1.00]; p = 0.019). The complete blood count, coagulation parameters, liver and renal function, although differed from gender categories, in the majority of cases were in the range of normality. The overall prevalence of chest X-ray abnormalities at presentation were comparable in men and women, as well as the unilateral or bilateral onset of viral pneumonia (Table 4).

Respiratory Support in the First 24 h and In-hospital Treatment

The type of support used to treat respiratory failure in the first 24 h and in-hospital treatment are shown in Table 3. In order to correct hypoxemia, 34.8% (n = 40) of women required low flow oxygen nasal cannula, whereas in men this treatment was sufficient in a lower percentage (i.e. 23.7% [n = 71], p = 0.022). Indeed, males necessitated CPAP more frequently than females at presentation (25.7% vs 13.0%; p = 0.006). Considering in-hospital treatments, no gender differences were observed, with the exception of IL-6 pathway inhibitors that were used only in 17 males.

Clinical Outcomes and Gender as Predictor of Mortality

Overall 28-day mortality occurred in 34.8% of the patients (150/431), of whom 26.1% (31/119) were women and 38.1% (119/312) were men (p = 0.018, Additional file 1: Table S2). Kaplan–Meier survival curve at 28-day (Figure 1) found a lower mortality for females (p = 0.021). The secondary outcome (i.e. development of severe disease) were reported in the 59.9% of the patients (258/431), and it occurred more frequently in male patients (63.1% (197/431) vs 51.3% (61/11); p = 0.024, Additional file 1: Table S2). When outcomes were stratified by age categories, no gender differences were noted (p = 0.091 and p = 0.052 for primary and secondary outcome, respectively, Additional file 1: Table S2).

Figure 1.

Kaplan–Meier 28-day mortality since hospitalization by gender in the overall population

Multivariable analysis aimed at evaluating independent predictors of mortality is shown in Table 5. When baseline demographic, clinical characteristics and pre-hospital epidemiologic and clinical features emerged by univariate analysis were included in the multivariable analysis, male sex, together with older age, immunosuppression and dyspnea resulted independent predictors of death. However, once the parameters related to the severity of disease at presentation (i.e. need of CPAP or NIV in the first 24 h, and PaO2/FiO2 < 200 mmHg at admission) were included in the model, gender did not result an independent predictor of death (p = 0.898, Table 5). Accordingly, Kaplan–Meier survival analysis at 28-day in patients who needed CPAP or NIV in the first 24 h did not find a significant difference between men and women (Figure 2, p = 0.687).

Figure 2.

Kaplan–Meier 28-day mortality since hospitalization by gender in patients who needed CPAP/NIV in the first 24 h. CPAP Continuous positive airway pressure, NIV non-invasive ventilation