The development of preventive and therapeutic vaccines has played a crucial role in preventing infections and treating chronic and non-communicable diseases, respectively. For a long time, the influence of sex differences on modifying health and disease has not been addressed in clinical and preclinical studies. The interaction of genetic, epigenetic, and hormonal factors plays a role in the sex-related differences in the epidemiology of diseases, clinical manifestations, and the response to treatment. Moreover, sex is one of the leading factors influencing the gut microbiota composition, which could further explain the different predisposition to diseases in men and women. In the same way, differences between sexes occur also in the immune response to vaccines. This narrative review aims to highlight these differences, focusing on the immune response to vaccines. Comparative data about immune responses, vaccine effectiveness, and side effects are reviewed. Hence, the intricate interplay between sex, immunity, and the gut microbiota will be discussed for its potential role in the response to vaccination. Embracing a sex-oriented perspective in research may improve the efficacy of the immune response and allow the design of tailored vaccine schedules.

All-cause mortality related to the SARS-CoV-2 infection has declined from the first wave to subsequent waves, probably through vaccination programs and the availability of effective antiviral therapies. Our study aimed to evaluate the impact of the SARS-CoV-2 vaccination on the prognosis of infected patients. Overall, we enrolled 545 subjects during the Delta variant wave and 276 ones during the Omicron variant wave. Data were collected concerning vaccination status, clinical parameters, comorbidities, lung involvement, laboratory parameters, and pharmacological treatment. Outcomes were admission to the intensive care unit (ICU) and 30-day all-cause mortality. Overall, the final sample included 821 patients with a mean age of 62 ± 18 years [range 18–100], and 59% were men. Vaccinated patients during the Delta wave were 37% (over ¾ with two doses), while during the Omicron wave they were 57%. Vaccinated patients were older (68 vs. 57 years), and 62% had at least one comorbidity Admission to the ICU was 20%, and the mortality rate at 30 days was 14%. ICU admissions were significantly higher during the Delta wave than during Omicron (OR 1.9, 95% CI 1.2–3.1), while all-cause mortality did not differ. Unvaccinated patients had a higher risk of ICU admission (OR 2.0, 95% CI 1.3–3.1) and 30-day all-cause mortality (OR 1.7, 95% CI 1.3–2.7). Results were consistent for both Delta and Omicron variants. Overall, vaccination with at least two doses was associated with a reduced need for ICU admission. Even one shot of the vaccine was associated with a significantly reduced 30-day mortality.

Background: Coronavirus Disease 2019 (COVID-19), triggered by SARS-CoV-2, has represented a global pandemic associated with an elevated rate of mortality, mainly among older individuals. The extensive pulmonary involvement by the viral infection might have precipitated pre-existing chronic conditions in this vulnerable population, including heart failure (HF). Materials and Methods: The aim of this retrospective, observational study was to assess the impact of COVID-19 in patients with a prior diagnosis of HF referred to the Emergency Department of the Agostino Gemelli University Hospital between March 2020 and January 2023. A total of 886 HF patients (444 men and 442 women, mean age of 80 ± 10 years) were identified. Patients were matched in a 1:1 ratio by gender, age, number of comorbidities (excluding HF), and vaccination status, using a propensity score matching (PSM) procedure. We compared the outcomes of 189 patients with a concomitant diagnosis of HF with those of 189 matched controls without HF. Results: Among patients with HF, there was a significantly higher prevalence of valvular disease (p = 0.004), atrial fibrillation (p = 0.003), use of anticoagulants (p = 0.001), chronic obstructive pulmonary diseases (p = 0.03), and chronic kidney disease (p = 0.001). In contrast, hypertension was more prevalent among controls than HF patients (p = 0.04). In addition, controls exhibited higher lymphocytes counts and a higher PaO₂/FiO₂ ratio compared to HF patients. During hospitalization, patients with HF were more frequently treated with high-flow nasal cannulas (p = 0.01), required more frequent admission to an intensive care unit (ICU) (p = 0.04), and showed a significantly higher mortality rate (p 0.0001) than controls. Conclusions: HF is an independent risk factor for ICU admission and death in COVID-19 patients.