Female gender is associated with long COVID syndrome: a prospective cohort study.

OBJECTIVE: We explored the association between female gender and long COVID syndrome, defined as persistence of physical and/or psychological symptoms for more than 4 weeks after recovery from acute COVID-19 disease. The secondary aim was to identify predictors of long COVID syndrome by multivariable logistic regression analysis. METHODS: This was a single-centre prospective cohort study conducted at San Paolo Hospital in Milan, Italy. We enrolled adult patients who were evaluated at the post-COVID outpatient service of our Infectious Diseases Unit between 15 April 2020 and 15 December 2020. Participants were individuals who had clinically recovered from COVID-19 and in whom virological clearance had occurred. Previous infection by SARS-CoV-2 was microbiologically documented by positivity using a reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab. All enrolled patients underwent blood tests and a comprehensive medical examination at follow-up. Individuals were interviewed about resolved and persisting symptoms and were asked to fill in two questionnaires to allow assessment of the Hospital Anxiety and Depression symptoms (HADS) score and of the Impact of Event Scale-Revised (IES-R) score. RESULTS: A total of 377 patients were enrolled in the study. The median time from symtpom onset to virological clerance was 44 (37-53) days. A diagnosis of long COVID syndrome was made in 260/377 (69%) patients. The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and "brain fog" (76/377, 20.2%). Anxiety symptoms were ascertained in 71/377 (18.8%) individuals, whereas 40/377 (10.6%) patients presented symptoms of depression. Post-traumatic stress disorder (defined by a pathological IES-R score) was diagnosed in one-third of patients (85/275, 31%). Female gender was independently associated with long COVID syndrome at multivariable analysis (AOR 3.3 vs. males, 95% CI 1.8-6.2, p < 0.0001). Advanced age (adjusted (A)OR 1.03 for 10 years older, 95% CI 1.01-1.05, p 0.01) and active smoking (AOR 0.19 for former smokers vs. active smokers, 95% CI 0.06-0.62, p 0.002) were also associated with a higher risk of long COVID, while no association was found between severity of disease and long COVID (AOR 0.67 for continuous positive airway pressure (CPAP)/non-invasive mechanical ventilation (NIMV)/orotracheal intubation (OTI) vs. no 02 therapy, 95% CI 0.29-1.55, p 0.85). DISCUSSION: Factors that were found to be associated with a higher risk of developing "long COVID" syndrome were female gender, older age and active smoking, but not severity of the acute disease. Individuals affected by SARS-CoV-2 infection with the aforementioned features should be early identified and involved in follow-up programmes.

Declining Mortality Rate of Hospitalised Patients in the Second Wave of the COVID-19 Epidemics in Italy: Risk Factors and the Age-Specific Patterns.

BACKGROUND: Mortality rate from COVID-19 in Italy is among the world's highest. We aimed to ascertain whether there was any reduction of in-hospital mortality in patients hospitalised for COVID-19 in the second-wave period (October 2020-January 2021) compared to the first one (February-May 2020); further, we verified whether there were clusters of hospitalised patients who particularly benefitted from reduced mortality rate. METHODS: Data collected related to in-patients' demographics, clinical, laboratory, therapies and outcome. Primary end-point was time to in-hospital death. Factors associated were evaluated by uni- and multivariable analyses. A flow diagram was created to determine the rate of in-hospital death according to individual and disease characteristics. RESULTS: A total of 1561 patients were included. The 14-day cumulative incidence of in-hospital death by competing risk regression was of 24.8% (95% CI: 21.3-28.5) and 15.9% (95% CI: 13.7-18.2) in the first and second wave. We observed that the highest relative reduction of death from first to second wave (more than 47%) occurred mainly in the clusters of patients younger than 70 years. CONCLUSIONS: Progress in care and supporting therapies did affect population over 70 years to a lesser extent. Preventive and vaccination campaigns should focus on individuals whose risk of death from COVID-19 remains high.