Excerpt
Since December 2019, when the Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) quickly spread throughout China and the rest of the world, more than 6 million people have died [
1]. The presence of age-related and sex-related disparities in the general population is well known and largely discussed in the literature. Elderly, especially with concomitant chronic non-communicable diseases, are the most vulnerable population, considering that people older than 65 years have strikingly higher mortality rates due to SARS-CoV-2 than younger people [
1]. To contain the wide diffusion of the virus, a global vaccination campaign has been established, leading to a remarkable and quick reduction in adverse outcomes, namely non-Intensive Care Unit (ICU) or ICU hospitalizations, and deaths [
2]. Sex differences play a role in COVID-19 pandemic, considering that, with the same rate of cases and vaccinations, adverse outcomes impact more on male individuals [
1]. However, there is a lack of information about sex-related differences in response to COVID-19 vaccination, especially in the most vulnerable population represented by older people. In this regard, the data provided by Trevisan et al. [
3] on this issue of Internal and Emergency Medicine provide several insights on this relevant topic, filling this knowledge gap about sex differences in the efficacy and safety of COVID-19 vaccines. The authors of this Italian-based multicenter study evaluated the rate of COVID-19 infection, frequency and types of adverse effects, and antibody response after vaccination in elderly and fragile residents in long-term care facilities (LTCF). The population enrolled was a cohort of 3259 (of which 71% were females) Italian residents with a mean age of 83.4 years. The authors performed a clinical monitoring after 7 days from the first, second, and booster doses of vaccine and after 2, 6, and 12 months from the first-dose administration collecting afterward the incidence of COVID-19, possible vaccine adverse effects, Emergency Department (ED) accesses, unplanned hospitalizations and mortality. In a largely representative subgroup of 524 participants, they also performed serological monitoring of anti-S IgG before the first vaccine dose administration and after 2, 6 and 12 months. For each participant, the authors also collected data about sex, age, functional status, co-morbidities and mobility level. The main findings are the absence of any difference in the incidence of infection by Sars-CoV-2 after vaccination between males and females. Females reported more local adverse effects after the first dose compare with males (13.3% vs 10.2%,
p = 0.018), while no sex-related difference is reported after following doses of vaccination. There is no sex-related difference in systemic adverse effects [
3]. The most important evidence concerns the antibody response to vaccines, in fact, the authors did not observe any differences in the IgG titer between males and females, regardless the infection by Sars-CoV-2 or the number of vaccine doses, a result in contrast with previous evidences on younger population [
4]. Multimorbidity was quite frequent in this cohort of LTCF, being patients affected by an average of 5 concomitant chronic diseases for each patient. Interestingly, the presence of some cluster of co-morbidities showed an impact on immune response after COVID-19 vaccination. Indeed, males with cardiovascular diseases (CVD) were more likely to have lower IgG titer than CVD-free ones [β-coefficient at 12 months − 0.411 (95% confidence interval − 0.731, − 0.091),
p < 0.05]. Also, females with diabetes mellitus [β-coefficient at 12 months − 0.290 (95% confidence interval − 0.546, − 0.033),
p < 0.05] or cognitive disorders [β-coefficient at 12 months − 0.272 (95% confidence interval − 0.501, − 0.043),
p < 0.05] had a lower antibody titer. Both males and females with mobility limitations were more likely to have higher levels in the antibody response [β-coefficient at 12 months for men 0.448 (95% confidence interval 0.090, 0.807) and for women 0.274 (95% confidence interval 0.053, 0.495),
p < 0.05], while both males and females with depressive disorder had lower levels in the antibody response [β-coefficient at 2 months for men − 0.330 (95% confidence interval − 0.589, − 0.071) and at 12 months for women − 0.235 (95% confidence interval − 0.441, − 0.028),
p < 0.05] [
3]. Summarizing, the COVID-19 vaccines are found to be effective in both sexes, and there is no strong sex-related difference in older patients in incidence of COVID-19, adverse effects, adverse outcomes and in antibody response even though the latter is influenced by concomitant chronic non-communicable diseases. The current work brings attention for the first time to a category of patients often overlooked by large trials. Indeed, the main finding is that concurrent chronic diseases in a fragile population of LTCF residents explains crucial differences in antibody titer response following vaccination against SARS-CoV-2. Another interesting aspect is the absence of rough sex-secondary differences in antibody response. However, as robust evidence has shown, understanding biological phenomena cannot stop at the gender divide alone, but must contemplate the far more complex socio-cultural construct of gender [
5]. Gender in fact stratifies the population more accurately by considering several factors belonging to the four domains of gender: identity, relations, role and institutionalized gender [
5]. The current work in fact lays the foundation for future research on antibody response in correlation with gender, which could be an extremely fascinating chapter of clinical research on the most groundbreaking topic in recent years. …
