Sex differences in the efficacy and safety of SARS-CoV-2 vaccination in residents of long-term care facilities: insights from the GeroCovid Vax study.

Despite the reported sex-related variations in the immune response to vaccination, whether the effects of SARS-CoV-2 vaccination differ by sex is still under debate, especially considering old vulnerable individuals, such as long-term care facilities (LTCFs) residents. This study aimed to evaluate COVID-19 infections, adverse events, and humoral response after vaccination in a sample of LTCF residents. A total of 3259 LTCF residents (71% females; mean age: 83.4 ± 9.2 years) were enrolled in the Italian-based multicenter GeroCovid Vax study. We recorded the adverse effects occurring during the 7 days after vaccine doses and COVID-19 cases over 12 months post-vaccination. In a subsample of 524 residents (69% females), pre- and post-vaccination SARS-CoV-2 trimeric S immunoglobulin G (Anti-S-IgG) were measured through chemiluminescent assays at different time points. Only 12.1% of vaccinated residents got COVID-19 during the follow-up, without any sex differences. Female residents were more likely to have local adverse effects after the first dose (13.3% vs. 10.2%, p = 0.018). No other sex differences in systemic adverse effects and for the following doses were recorded, as well as in anti-S-IgG titer over time. Among the factors modifying the 12-month anti-S-IgG titers, mobility limitations and depressive disorder were more likely to be associated with higher and lower levels in the antibody response, respectively; a significantly lower antibody titer was observed in males with cardiovascular diseases and in females with diabetes or cognitive disorders. The study suggests that, among LTCF residents, SARS-CoV-2 vaccination was effective regardless of sex, yet sex-specific comorbidities influenced the antibody response. Local adverse reactions were more common in females.

Sex and Gender Impact Mental and Emotional Well-Being During COVID-19 Pandemic: A European Countries Experience.

Objective: The COVID-19 pandemic influences mental health drastically. Therefore, our aim was to investigate whether biological sex and gender-related factors are associated with mental health during the COVID-19 pandemic. Materials and Methods: The International COVID-19 Awareness and Responses Evaluation Study is an international multiwave cross-sectional observational cohort study of public awareness, attitudes, and responses to public health policies (www.mbmc- cmcm.ca/covid19). The study is led by the Montreal Behavioural Medicine Centre in collaboration with 200 international collaborators from 42 countries. It has received research ethics board approval from the Comité d'éthique de recherche du CIUSSS-NIM (Centre intégré universitaire de santé et de services sociaux du Nord- de-l'île-de-Montréal), approval no.: 2020-2099/25-03-2020. Recruitment began on March 27, 2020, and the survey is available in 34 languages. The associations between biological sex, sociocultural gender, and mental health were assessed in multivariate logistic regression models only for the European population (n = 12,300). Results: Positive correlations were found between female sex and "feeling nervous, anxious or worried" (OR = 3.2, p < 0.001, 95% CI 1.87-5.63) and "feeling sad, depressed or hopeless" (OR 1.8, p = 0.031, CI 1.05-3.05). Male sex was related to more frequently "feeling irritable, frustrated, and angry" (OR = 1.8, p = 0.04, 95% CI 1.03-2.99). Concerning gender, a negative correlation between being employed and "feeling lonely or isolated" (OR = 0.26, p < 0.001, 95% CI 0.11-0.59) was observed in the female cohort. Conclusion: Sex and gender differences exist in the emotional responses during the COVID-19 pandemic. Especially, within the female cohort, unemployment is negatively associated with mental health. Therefore, this study suggests more targeted psychological and social support for females during the pandemic.

Importance of sex and gender factors for COVID-19 infection and hospitalisation: a sex-stratified analysis using machine learning in UK Biobank data.

OBJECTIVE: To examine sex and gender roles in COVID-19 test positivity and hospitalisation in sex-stratified predictive models using machine learning. DESIGN: Cross-sectional study. SETTING: UK Biobank prospective cohort. PARTICIPANTS: Participants tested between 16 March 2020 and 18 May 2020 were analysed. MAIN OUTCOME MEASURES: The endpoints of the study were COVID-19 test positivity and hospitalisation. Forty-two individuals' demographics, psychosocial factors and comorbidities were used as likely determinants of outcomes. Gradient boosting machine was used for building prediction models. RESULTS: Of 4510 individuals tested (51.2% female, mean age=68.5±8.9 years), 29.4% tested positive. Males were more likely to be positive than females (31.6% vs 27.3%, p=0.001). In females, living in more deprived areas, lower income, increased low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio, working night shifts and living with a greater number of family members were associated with a higher likelihood of COVID-19 positive test. While in males, greater body mass index and LDL to HDL ratio were the factors associated with a positive test. Older age and adverse cardiometabolic characteristics were the most prominent variables associated with hospitalisation of test-positive patients in both overall and sex-stratified models. CONCLUSION: High-risk jobs, crowded living arrangements and living in deprived areas were associated with increased COVID-19 infection in females, while high-risk cardiometabolic characteristics were more influential in males. Gender-related factors have a greater impact on females; hence, they should be considered in identifying priority groups for COVID-19 infection vaccination campaigns.

Impact of biological sex and gender-related factors on public engagement in protective health behaviours during the COVID-19 pandemic: cross-sectional analyses from a global survey.

OBJECTIVE: Given the role of sociocultural gender in shaping human behaviours, the main objective of this study was to examine whether sex and gender-related factors were associated with the public's adherence to COVID-19-recommended protective health behaviours. DESIGN: This was a retrospective analysis of the survey that captured data on people's awareness, attitudes and behaviours as they relate to the COVID-19 policies. SETTING: Data from the International COVID-19 Awareness and Responses Evaluation survey collected between March 2020 and February 2021 from 175 countries. PARTICIPANTS: Convenience sample around the world. MAIN OUTCOME MEASURES: We examined the role of sex and gender-related factors in relation to non-adherence of protective health behaviours including: (1) hand washing; (2) mask wearing; and (3) physical distancing. Multivariable logistic regression was conducted to determine the factors associated with non-adherence to behaviours. RESULTS: Among 48 668 respondents (mean age: 43 years; 71% female), 98.3% adopted hand washing, 68.5% mask wearing and 76.9% physical distancing. Compared with males, females were more likely to adopt hand washing (OR=1.97, 95% CI: 1.71 to 2.28) and maintain physical distancing (OR=1.28, 95% CI: 1.22 to 1.34). However, in multivariable sex-stratified models, females in countries with higher Gender Inequality Indexes (GII) were less likely to report hand washing (adjusted OR (aOR)=0.47, 95% CI: 0.21 to 1.05). Females who reported being employed (aOR=0.22, 95% CI: 0.10 to 0.48) and in countries with low/medium GIIs (aOR=0.18, 95% CI 0.06 to 0.51) were less likely to report mask wearing. Females who reported being employed were less likely to report physical distancing (aOR=0.39, 95% CI: 0.32 to 0.49). CONCLUSION: While females showed greater adherence to COVID-19 protective health behaviours, gender-related factors, including employment status and high country-wide gender inequality, were independently associated with non-adherence. These findings may inform public health and vaccination policies in current as well as future pandemics.

Platelet and immune signature associated with a rapid response to the BNT162b2 mRNA COVID-19 vaccine.

BACKGROUND: A rapid immune response is critical to ensure effective protection against COVID-19. Platelets are first-line sentinels of the vascular system able to rapidly alert and stimulate the immune system. However, their role in the immune response to vaccines is not known. OBJECTIVE: To identify features of the platelet-immune crosstalk that would provide an early readout of vaccine efficacy in adults who received the mRNA-based COVID-19 vaccine (BNT162b2). METHODS: We prospectively enrolled 11 young healthy volunteers (54% females, median age: 28 years) who received two doses of BNT162b2, 21 days apart, and we studied their platelet and immune response before and after each dose of the vaccine (3 and 10 ± 2 days post-injection), in relation to the kinetics of the humoral response. RESULTS: Participants achieving an effective level of neutralizing antibodies before the second dose of the vaccine (fast responders) had a higher leukocyte count, mounted a rapid cytokine response that incremented further after the second dose, and an elevated platelet turnover that ensured platelet count stability. Their circulating platelets were not more reactive but expressed lower surface levels of the immunoreceptor tyrosine-based inhibitory motif (ITIM)-coupled receptor CD31 (PECAM-1) compared to slow responders, and formed specific platelet-leukocyte aggregates, with B cells, just 3 days after the first dose, and with non-classical monocytes and eosinophils. CONCLUSION: We identified features of the platelet-immune crosstalk that are associated with the development of a rapid humoral response to an mRNA-based vaccine (BNT162b2) and that could be exploited as early biomarkers of vaccine efficacy.

Healthcare workers' perception of gender and work roles during the COVID-19 pandemic: a mixed-methods study.

OBJECTIVES: A high functioning healthcare workforce is a key priority during the COVID-19 pandemic. We sought to determine how work and mental health for healthcare workers changed during the COVID-19 pandemic in a universal healthcare system, stratified by gender factors. DESIGN: A mixed-methods study was employed. Phase 1 was an anonymous, internet-based survey (7 May-15 July 2020). Phase 2 was semistructured interviews offered to all respondents upon survey completion to describe how experiences may have differed by gender identity, roles and relations. SETTING: National universal healthcare system (Canada). PARTICIPANTS: 2058 Canadian healthcare worker survey respondents (87% women, 11% men, 1% transgender or Two-Spirit), including 783 health professionals, 673 allied health professionals, 557 health support staff. Of the 63 unique healthcare worker types reported, registered nurses (11.5%), physicians (9.9%) and pharmacists (4.5%) were most common. Forty-six healthcare workers were interviewed. MAIN OUTCOME MEASURES: Reported pandemic-induced changes to occupational leadership roles and responsibilities, household and caregiving responsibilities, and anxiety levels by gender identity. RESULTS: Men (19.8%) were more likely to hold pandemic leadership roles compared with women (13.4%). Women (57.5%) were more likely to report increased domestic responsibilities than men (45%). Women and those with dependents under the age of 10 years reported the greatest levels of anxiety during the pandemic. Interviews with healthcare workers further revealed a perceived imbalance in leadership opportunities based on gender identity, a lack of workplace supports disproportionately affecting women and an increase in domestic responsibilities influenced by gender roles. CONCLUSIONS: The COVID-19 pandemic response has important gendered effects on the healthcare workforce. Healthcare workers are central to effective pandemic control, highlighting an urgent need for a gender-transformative pandemic response strategy.

Public perceptions and behavioural responses to the first COVID-19 pandemic wave in Italy: results from the iCARE study.

BACKGROUND: Italy was the first European country to be affected by COVID-19. Considering that many countries are currently battling the second wave of the pandemic, understanding people's perceptions and responses to government policies remain critical for informing on-going mitigation strategies. We assessed attitudes towards COVID-19 policies, levels of adherence to preventive behaviours, and the association between COVID-19 related concerns and adherence levels. METHODS: We recruited a convenience sample of Italian individuals from an international cross-sectional survey (www.icarestudy.com) from 27 March to 5 May 2020. Multivariate regression models were used to test the association between concerns and the adoption of preventive measures. RESULTS: The survey included 1332 participants [female (68%), younger than 25 (57%)] that reported high awareness (over 96%) and perceived importance (88%) of policies. We observed varied levels of adherence to: hand-washing (96%), avoiding social gatherings (96%), self-isolation if suspected or COVID-19 positive (77%). Significantly lower adherence to self-isolation was reported by individuals with current employment. High levels of concerns regarding health of other individuals and country economy were reported. Only health concerns for others were significantly associated with higher adherence to hand-washing behaviour. CONCLUSIONS: In order to inform current/future government strategies, we provide insights about population's responses to the initial pandemic phase in Italy. Communication approaches should consider addressing people's concerns regarding the health of other individuals to motivate adherence to prevention measures. Provision of social and economic support is warranted to avoid unequal impacts of governmental policies and allow effective adherence to self-isolating measures.

Rethinking of osteoporosis through a sex- and gender-informed approach in the COVID-19 era.

Standards and models of reference for osteoporosis (OP) have been developed for female individuals as they are more likely to be affected by the disease. Nonetheless, OP is also responsible for one-third of hip fractures in male individuals suggesting that a sex-blinded approach to OP may lead to miss opportunities for equity in bone health. OP-related fractures, especially hip fractures, are a matter of immediate concern as they are associated with limited mobility, chronic disability, loss of independence, and reduced quality of life in both sexes. When it comes to sociocultural gender, the effect of gender domains (i.e., identity, roles, relations, and institutionalized gender) on development and management of OP is largely overlooked despite risk factors or protective conditions are gendered. Clinical trials testing the efficacy and safety of anti-OP drugs as well as non-pharmacological interventions have been conducted mainly in female participants, limiting the generalizability of the findings. The present narrative review deals with the sex and gender-based challenges and drawbacks in OP knowledge and translation to clinical practice, also considering the impact of coronavirus disease 2019 pandemic.

Prevalence and clinical correlates of dementia among COVID-19-related deaths in Italy.

INTRODUCTION: We aimed at exploring the proportion of patients dying with COVID-19 and concomitant dementia in Italy, as well as their clinical characteristics and trajectories of care. METHODS: The proportion of COVID-19-related deaths occurring in people with dementia and the clinical characteristics of deceased individuals according to their dementia status were explored by considering the medical charts of a representative sample of patients deceased in Italian hospitals (n = 2621). RESULTS: A total of 415 individuals with dementia were identified in the study population, accounting for 15.8% of overall COVID-19-related deaths. Patients with dementia less frequently presented with cough, had lower chance of receiving supportive therapies and intensive care approaches, and showed a faster clinical worsening as compared with individuals with intact cognition. DISCUSSION: Dementia confers a relevant risk of adverse outcomes in case of SARS-CoV-2 infection and influences the clinical presentation, course and management of affected individuals.

Sex differences in clinical phenotype and transitions of care among individuals dying of COVID-19 in Italy.

BACKGROUND: Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available. METHODS: A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27-June 11, 2020). Clinical characteristics and the times from symptoms' onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex. RESULTS: Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39-2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29-2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13-1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55-0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25-0.63), yet both sexes had a high level of multimorbidity. The times from symptoms' onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45-5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13-1.90). CONCLUSIONS: Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.

The Pipeline of Therapeutics Testing During the Emergency Phase of the COVID-19 Outbreak.

The coronavirus disease 19 (COVID-19) pandemic poses a serious threat to the sustainability of healthcare systems and is currently having a significant effect on living conditions worldwide. No therapeutic agent has yet proven to be effective for the treatment of COVID-19. The management of this disease currently relies on supportive care and the off-label and compassionate use of antivirals and immunomodulators. Nevertheless, there has been a great worldwide effort to progress research and test the efficacy and safety/tolerability profiles of numerous candidate agents that may positively affect the various clinical syndromes associated with COVID-19. In parallel, vaccination and chemoprophylaxis strategies are being investigated. This article provides a summary of interventional studies targeting COVID-19 during the emergency phase of the outbreak to broadly inform clinicians and researchers on what happened and what they can expect in upcoming months. The clinicaltrials.gov database and the European Union (EU) Clinical Trials Register were investigated on March 31, 2020, to identify all ongoing phase 1-4 research protocols testing pharmacological interventions targeting SARS-CoV-2 infection and/or clinical syndromes associated with COVID-19. Overall, six phase 1, four phase 1-2, 14 phase 2, ten phase 2-3, 19 phase 3, and nine phase 4 studies were identified, and the features of these studies are described in the present review. We also provide an updated overview of the change overtime in the pipeline following this emergency phase and based on the current epidemiology of the COVID-19 pandemic.

COVID-19 mortality among migrants living in Italy.

We aimed to compare COVID-19-specific and all-cause mortality rates among natives and migrants in Italy and to investigate the clinical characteristics of individuals dying with COVID-19 by native/migrant status. The mortality rates and detailed clinical characteristics of natives and migrants dying with COVID-19 were explored by considering the medical charts of a representative sample of patients deceased in Italian hospitals (n = 2,687) between February 21st and April 29th, 2020. The migrant or native status was assigned based on the individual's country of birth. The expected all-cause mortality among natives and migrants living in Italy was derived by the last available (2018) dataset provided by the Italian National Institute of Statistics. Overall, 68 individuals with a migration background were identified. The proportions of natives and migrants among the COVID-19-related deaths (97.5% and 2.5%, respectively) were similar to the relative all-cause mortality rates estimated in Italy in 2018 (97.4% and 2.6%, respectively). The clinical phenotype of migrants dying with COVID-19 was similar to that of natives except for the younger age at death. International migrants living in Italy do not have a mortality advantage for COVID-19 and are exposed to the risk of poor outcomes as their native counterparts.

Cardiovascular Pathophysiology, Epidemiology, and Treatment Considerations of Coronavirus Disease 2019 (COVID-19): A Review.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly evolving, with important cardiovascular considerations. The presence of underlying cardiovascular risk factors and established cardiovascular disease (CVD) may affect the severity and clinical management of patients with COVID-19. We conducted a review of the literature to summarize the cardiovascular pathophysiology, risk factors, clinical presentations, and treatment considerations of COVID-19 patients with underlying CVD. Angiotensin-converting enzyme 2 (ACE2) has been identified as a functional receptor for the SARS-CoV-2 virus, and it is associated with the cardiovascular system. Hypertension, diabetes, and CVD are the most common comorbidities in COVID-19 patients, and these factors have been associated with the progression and severity of COVID-19. However, elderly populations, who develop more-severe COVID-19 complications, are naturally exposed to these comorbidities, underscoring the possible confounding of age. Observational data support international cardiovascular societies' recommendations to not discontinue ACE inhibitor/angiotensin-receptor blocker therapy in patients with guideline indications for fear of the increased risk of SARS-CoV-2 infection, severe disease, or death. In addition to the cardiotoxicity of experimental antivirals and potential interactions of experimental therapies with cardiovascular drugs, several strategies for cardiovascular protection have been recommended in COVID-19 patients with underlying CVD. Troponin elevation is associated with increased risk of in-hospital mortality and adverse outcomes in patients with COVID-19. Cardiovascular care teams should have a high index of suspicion for fulminant myocarditis-like presentations being SARS-CoV-2 positive, and remain vigilant for cardiovascular complications in COVID-19 patients.

La pandémie de la maladie à coronavirus 2019 (COVID-19) causée par le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) évolue rapidement, et des considérations cardiovasculaires importantes y sont rattachées. La présence de facteurs de risque cardiovasculaire sous-jacents ou d'une maladie cardiovasculaire (MCV) établie peut influer la gravité de la COVID-19 et la prise en charge des patients qui en sont atteints. Nous avons effectué une revue de la littérature afin de résumé la physiopathologie cardiovasculaire, les facteurs de risque, les manifestations cliniques et les traitements à considérer pour les patients atteints de la COVID-19 et présentant une MCV sous-jacente. L'enzyme de conversion de l'angiotensine 2 (ECA2), qui intervient dans le système cardiovasculaire, a été identifiée comme étant un récepteur fonctionnel du SRAS-CoV-2. L'hypertension, le diabète et la MCV sont les affections concomitantes les plus fréquentes chez les patients atteints de la COVID-19, et ces facteurs ont été associés à l'évolution et à la gravité de la COVID-19. Les personnes âgées, chez qui les complications de la COVID-19 sont plus graves, sont cependant naturellement plus exposées à ces affections, ce qui fait ressortir l'âge comme étant un facteur de confusion possible. Les données d'observation soutiennent les recommandations des organismes internationaux s'intéressant à la santé cardiovasculaire, qui sont de ne pas cesser le traitement d'inhibiteur d'enzyme de conversion de l'angiotensine ou d'antagoniste des récepteurs de l'angiotensine lorsque ces traitements sont indiqués selon les lignes directrices, par crainte d'accroître le risque de maladie grave ou de décès pour les patients atteints par le SRAS-CoV-2. Compte tenu des effets cardiotoxiques des antiviraux expérimentaux et des interactions possibles entre les traitements expérimentaux et les médicaments utilisés pour traiter les MCV, plusieurs stratégies de protection cardiovasculaire ont été recommandées pour le traitement des patients atteints de la COVID-19 présentant une MCV sous-jacente. L'élévation de la troponine est associée à un risque accru de mortalité hospitalière et à des résultats défavorables pour les patients atteints de la COVID-19. Les équipes de soins cardiovasculaires doivent toujours garder à l'esprit qu'un patient présentant des symptômes évocateurs d'une myocardite fulminante pourrait être infecté par le SRAS-CoV-2 et surveiller les complications cardiovasculaires chez les patients atteints de la COVID-19.

Clinical Characteristics of Hospitalized Individuals Dying With COVID-19 by Age Group in Italy.

BACKGROUND: Aim of the present study is to describe characteristics of COVID-19-related deaths and to compare the clinical phenotype and course of COVID-19-related deaths occurring in adults (<65 years) and older adults (≥65 years). METHOD: Medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged ≥65 years) were revised to extract information on demographics, preexisting comorbidities, and in-hospital complications leading to death. RESULTS: Older adults (≥65 years) presented with a higher number of comorbidities compared to those aged <65 years (3.3 ± 1.9 vs 2.5 ± 1.8, p < .001). Prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, hypertension, dementia, COPD, and chronic renal failure was higher in older patients (≥65 years), while obesity, chronic liver disease, and HIV infection were more common in younger adults (<65 years); 10.9% of younger patients (<65 years) had no comorbidities, compared to 3.2% of older patients (≥65 years). The younger adults had a higher rate of non-respiratory complications than older patients, including acute renal failure (30.0% vs 20.6%), acute cardiac injury (13.5% vs 10.3%), and superinfections (30.9% vs 9.8%). CONCLUSIONS: Individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occur in healthy adults with no preexisting conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications.