Sex differences in a cohort of COVID-19 Italian patients hospitalized during the first and second pandemic waves
Authors: Quaresima Virginia , Scarpazza Cristina , Sottini Alessandra , Fiorini Chiara , Signorini Simona , Delmonte Ottavia Maria , Signorini Liana , Quiros-Roldan Eugenia , Imberti Luisa 
Published: August 2021

Abstract
Background
Coronavirus disease 2019 (COVID-19) severity seems to be influenced by genetic background, sex, age, and presence of specific comorbidities. So far, little attention has been paid to sex-specific variations of demographic, clinical, and laboratory features of COVID-19 patients referred to the same hospital in the two consecutive pandemic waves.

Methods
Demographic, clinical, and laboratory data were collected in 1000 COVID-19 patients (367 females and 633 males), 500 hospitalized in the first wave and 500 in the second one, at the ASST Spedali Civili of Brescia from March to December 2020. Statistical analyses have been employed to compare data obtained in females and males, taking into account their age, and during the first and second COVID-19 waves.

Results
The mean age at the time of hospitalization was similar in females and males but was significantly higher for both in the second wave; the time elapsed from symptom onset to hospital admission did not differ between sexes in the two waves, and no correlation was observed between delayed hospital admission and length of hospitalization. The number of multi-symptomatic males was higher than that of females, and patients with a higher number of comorbidities were more frequently admitted to intensive care unit (ICU) and more frequently died. Older males remained in the ICU longer than females and showed a longer disease duration, mainly the first wave. The highest levels of white blood cells, neutrophils, C-reactive protein, and fibrinogen were significantly higher in males and in the first, and along with higher levels of D-dimer, ferritin, lactate dehydrogenase, and procalcitonin which were preferentially documented in patients requiring ICU or died. While the rate of death in ICU was higher in males, the overall death rate did not differ between the sexes; however, the deceased women were older.

Conclusions
These data indicate that once patients were hospitalized, the risk of dying was similar between females and males. Therefore, future studies should aim at understanding the reasons why, for a given number of SARS-CoV-2 infections, fewer females develop the disease requiring hospitalization.

Highlights

Although the hospitalized males were significantly more, the similar number of hospitalizations of the > 75-year-old females and males could be due to the fact that in Brescia province, elderly women are about twice as many as men.

Although males spent more days in the hospital, had a longer disease duration, developed a critical illness more frequently, and were admitted and died in the ICU more than females, the total rate of deaths among patients was not significantly different between sexes.

Overall, the most frequent comorbidities were cardiovascular diseases, which were preferentially seen among patients hospitalized in the second wave; it is possible that the knowledge gained in the first wave concerning the association between certain comorbidities and worse disease evolution has guided the preferential hospitalization of patients with these predominant comorbidities.