Sex Differences in the Immunogenicity and Efficacy of Seasonal Influenza Vaccines: A Meta-analysis of Randomized Controlled Trials.

Background: Sex impacts individuals' response to vaccination. However, most vaccine studies do not report these differences disaggregated by sex. The aim of this study was to assess sex differences in the immunogenicity and efficacy of influenza vaccine. Methods: We performed a meta-analysis using phase 3 randomized controlled trial data conducted between 2010 and 2018. Using hemagglutination inhibition antibody titers for each strain, differences in geometric mean ratios (GMRs) were calculated by sex. Risk ratios (RRs) comparing seroconversion proportions were pooled for females and males using random-effects models. Vaccine efficacy (VE) was assessed. Data were analyzed by age group (18-64 vs ≥65 years). Results: A total of 33 092 healthy adults from 19 studies were included for immunogenicity analysis, and 6740 from 1 study for VE. Whereas no sex differences in immunogenicity were found in adults <65 years old, older females had a significantly greater chance to seroconvert compared to older males for all strains: RRH1N1 = 1.17 [95% confidence interval {CI}, 1.12-1.23]; RRH3N2 = 1.09 [95% CI, 1.05-1.14]; RRVictoria = 1.23 [95% CI, 1.14-1.31]; RRYamagata = 1.22 [95% CI, 1.14-1.30]. GMRs were also higher in older females for all strains compared to older males. VE in preventing laboratory-confirmed influenza was higher in older females compared to older males with VEs of 27.32% (95% CI, 1.15%-46.56%) and 6.06% (95% CI, -37.68% to 35.90%), respectively. Conclusions: Our results suggest a higher immunogenicity and VE in females compared to males in older adults. These differences in immunogenicity and VE support the disaggregation of vaccine data by sex in clinical trials and observational studies. Clinical Trials Registration: CRD42018112260.

Incidence and risk factors for recurrent Clostridioides difficile infection in pediatric at-risk groups in selected Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) hospitals.

OBJECTIVES: Incidence and risk factors for recurrent Clostridioides difficile infection (rCDI) are well established in adults, though data are lacking in pediatrics. We aimed to determine incidence of and risk factors for rCDI in pediatrics. METHODS: This retrospective cohort study of pediatric patients was conducted at 3 tertiary-care hospitals in Canada with laboratory-confirmed CDI between April 1, 2012, and March 31, 2017. rCDI was defined as an episode of CDI occurring 8 weeks or less from diagnostic test date of the primary episode. We used logistic regression to determine and quantify risk factors significantly associated with rCDI. RESULTS: In total, 286 patients were included in this study. The incidence proportion for rCDI was 12.9%. Among hospitalized patients, the incidence rate was estimated at 2.6 cases of rCDI per 1,000 hospital days at risk (95% confidence interval [CI], 1.7-3.9). Immunocompromised patients had higher incidence of rCDI (17.5%; P = .03) and higher odds of developing rCDI independently of antibiotic treatment given for the primary episode (odds ratio [OR], 2.31; 95% CI, 1.12-5.09). Treatment with vancomycin monotherapy did not show statistically significant protection from rCDI, independently of immunocompromised status (OR, 0.33; 95% CI, 0.05-1.15]). CONCLUSIONS: The identification of increased risk of rCDI in immunocompromised pediatric patients warrants further research into alternative therapies, prophylaxis, and prevention strategies to prevent recurrent disease burden within these groups. Treatment of the initial episode with vancomycin did not show statistically significant protection from rCDI.

Sex differences in adverse events following seasonal influenza vaccines: a meta-analysis of randomised controlled trials.

BACKGROUND: Despite being a vaccine-preventable disease, influenza remains a major public health threat with vaccine safety concerns reducing vaccine acceptability. Immune responses to vaccines and adverse events may differ between males and females, but most studies do not report results by sex. Using data from clinical trials, we explored sex differences in adverse events following seasonal influenza vaccines. METHODS: We obtained data for phase III randomised controlled trials identified through a systematic review and clinical trials registries, and performed a two-stage meta-analysis. Risk ratios (RR) and 95% confidence intervals (95% CI) comparing solicited reactions in females versus males were pooled using the Mantel-Haenszel method and a random-effects model. We used the ROBINS-I tool to assess risk of bias and the I2 statistic for heterogeneity. Main analysis was stratified by age: 18-64 years and ≥65 years. RESULTS: The dataset for this analysis included 34 343 adults from 18 studies (12 with individual-level data and 6 with aggregate data). There was a higher risk of injection site reactions in females compared with males for both younger and older participants, with RRs of 1.29 (95% CI 1.21 to 1.37) and 1.43 (95% CI 1.28 to 1.60), respectively. Higher risk in females was also observed for systemic reactions, with RRs of 1.25 (95% CI 1.20 to 1.31) and 1.27 (95% CI 1.20 to 1.34) for younger and older participants, respectively. We also observed elevated risks of severe reactions in females, with a higher RR in younger versus older participants for systemic reactions (RRs 2.12 and 1.48, p=0.03, I2=79.7%). RRs were not found to vary between quadrivalent and trivalent vaccines. CONCLUSION: This meta-analysis suggested a higher risk of solicited reactions following influenza vaccines for females compared with males, irrespective of age and vaccine type. Transparent communication of this risk could increase the trust in vaccines and limit vaccine hesitancy. Future studies should report results stratified by sex and explore the role of gender in the occurrence of adverse events.

Antiviral use in healthcare workers-A systematic review.

Neuraminidase inhibitors (NAIs) are likely part of the rapid response and control in influenza pandemics and institutional outbreaks. We conducted a systematic review to appraise the current evidence on the use of NAIs among healthcare workers in the context of an influenza pandemic.

The REinfection in COVID-19 Estimation of Risk (RECOVER) study: Reinfection and serology dynamics in a cohort of Canadian healthcare workers.

BACKGROUND: Understanding the immune response to natural infection by SARS-CoV-2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection. METHODS: We conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR-confirmed SARS-CoV-2 infection to (i) measure the average incidence rate of reinfection and (ii) describe the serological immune response to the primary infection. RESULTS: Our cohort comprised 569 HCWs; median duration of individual follow-up was 371 days. We detected six cases of reinfection in absence of vaccination between August 21, 2020, and March 1, 2022, for a reinfection incidence rate of 4.0 per 100 person-years. Median duration of seropositivity was 415 days in symptomatics at primary infection compared with 213 days in asymptomatics (p < 0.0001). Other characteristics associated with prolonged seropositivity for IgG against the spike protein included age over 55 years, obesity, and non-Caucasian ethnicity. CONCLUSIONS: Among unvaccinated healthcare workers, reinfection with SARS-CoV-2 following a primary infection remained rare.

Is there a difference in the immune response, efficacy, effectiveness and safety of seasonal influenza vaccine in males and females? - A systematic review.

INTRODUCTION: Seasonal influenza is an important cause of morbidity and mortality, despite being vaccine-preventable. Sex factors (genes and hormones) seem to impact individuals' susceptibility to infectious diseases and their response to vaccination. However, most vaccine studies do not explicitly assess sex differences in vaccine response, but rather adjust for sex. METHODS: We conducted a systematic review to analyze immunogenicity, efficacy, effectiveness and/or safety of seasonal influenza vaccine data stratified by sex. We searched PubMed, EMBASE, CINAHL, Web of Science and clinicaltrials.gov for observational studies and phase III/IV trials from January 1990 to June 2018, published in English or French. Two reviewers independently screened all references, then proceeded to data extraction and quality assessment using the Cochrane tools (RoB and ROBINS-I) on included studies. RESULTS: Of the 5,745 citations retrieved, 46 studies were included in the SR. Overall, 18 studies assessed immunogenicity, 1 estimated efficacy, 6 measured effectiveness and 25 evaluated safety of seasonal influenza vaccine in females and males (four studies reported on two sex-stratified outcomes concomitantly). CONCLUSION: No clear conclusion could be drawn regarding the effect of sex on the immunogenicity and effectiveness of seasonal influenza vaccine, but higher rates of adverse events following immunization (AEFIs) were reported in females. The heterogeneity of data and studies' low quality prevented us from conducting a meta-analysis. There is a need to emphasize on the appropriate use of the terms sex and gender in biomedical research. Evidence of higher quality is needed to better understand sex differences in response to influenza vaccine.

Impact of influenza vaccination on healthcare utilization - A systematic review.

INTRODUCTION: Although a vaccine-preventable disease, influenza causes approximately 3-5 million cases of severe illness and about 290,000-650,000 deaths worldwide, which occur primarily among people 65 years and older. Nonetheless, prevention of influenza and its complications rely mainly on vaccination. We aimed to systematically evaluate influenza vaccine effectiveness at reducing healthcare utilization in older adults, defined as the reduction of outpatient visits, ILI and influenza hospitalizations, utilization of antibiotics and cardiovascular events by vaccination status during the influenza season. METHODS: We searched MEDLINE, EMBASE, CINAHL, Cochrane Library and considered any seasonal influenza vaccine, excluding the pandemic (2009-10 season) vaccine. Reviewers independently assessed data extraction and quality assessment. RESULTS: Of the 8308 citations retrieved, 22 studies were included in the systematic review. Overall, two studies (9%) were deemed at moderate risk of bias, thirteen (59%) at serious risk of bias and seven (32%) at critical risk of bias. For outpatient visits, we found modest evidence of protection by the influenza vaccine. For all-cause hospitalization outcomes, we found a wide range of results, mostly deemed at serious risk of bias. The included studies suggested that the vaccine may protect older adults against influenza hospitalizations and cardiovascular events. No article meeting our inclusion criteria explored the use of antibiotics and ILI hospitalizations. The high heterogeneity between studies hindered the aggregation of data into a meta-analysis. CONCLUSION: The variability between studies prevented us from drawing a clear conclusion on the effectiveness of the influenza vaccine on healthcare utilization in older adults. Overall, the data suggests that the vaccine may result in a reduction of healthcare utilization in the older population. Further studies of higher quality are necessary.