Omicron incidence and seroprevalence among children in Montreal, Canada, in early 2023: final results from the longitudinal EnCORE serology study.

Since early 2022, routine testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on symptoms and exposure history has largely ceased in Canada. Consequently, seroprevalence studies, particularly longitudinal studies, have become critical for monitoring the rate of incident SARS-CoV-2 infections and the proportion of the population with evidence of immunity. EnCORE is a longitudinal SARS-CoV-2 seroprevalence study comprising five rounds of serology testing from October 2020 to June 2023, in a sample of 2- to 17-year-olds (at baseline), recruited from daycares and schools in four neighbourhoods of Montreal, Canada. We report on SARS-CoV-2 incidence and seroprevalence among the 509 participants in the fifth and final round of the study. Seroprevalence of antibodies from either infection or vaccination was 98% (95 per cent confidence interval [CI]: 97, 99). The infection-acquired seroprevalence was 78% (95% CI: 73-82), and the incidence rate was 113 per 100 person-years (95% CI: 94-132), compared to the seroprevalence of 58% and the incidence rate of 133 per 100 person-years, respectively, in the fourth round of testing (mid-late 2022). Of the 131 participants newly seropositive for infection in Round 4, only 18 were seronegative for infection in Round 5 (median follow-up: 326 days).

Effectiveness of the ten- and thirteen-valent pneumococcal conjugate vaccines to prevent serotype 19A invasive pneumococcal disease in Quebec, Canada. A Canadian immunization research network (CIRN) study.

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7, PCV10, PCV13 and a mixed PCV10/PCV13 schedule were sequentially used without catch-up. The effectiveness of vaccination schedules to prevent serotype 19A invasive pneumococcal disease (IPD) in <5-year-old children was estimated by the indirect cohort method during 2009-2023. A total of 248 19A IPD cases and 457 IPD controls were included in the analysis. Adjusted vaccine effectiveness (VEa) for ≥1 dose was 57 % [95 %CI: -1 %,82 %] for PCV10 and 62 % [16 %,83 %] for PCV13. VEa for 3 doses was 69 % [17 %,88 %] for PCV10, 76 % [39 %,90 %] for PCV13 and 86 % [64 %,95 %] for the 2PCV10 + 1PCV13 schedule. Protection provided by the PCV10-only schedule tended to be of lower magnitude compared to the two other schedules. The mixed PCV10 + PCV13 schedule showed a protection against 19A IPD at least comparable to that of 3 PCV-13 doses.

Genomic Epidemiology of Mycobacterium abscessus on the Island of Montréal Not Suggestive of Healthcare-associated Person-to-Person Transmission.

BACKGROUND: Mycobacterium abscessus complex (MABC), an opportunistic nontuberculous mycobacteria (NTM), can lead to poor clinical outcomes in pulmonary infections. Conflicting data exist on person-to-person transmission of MABC within and across healthcare facilities. To investigate further, a comprehensive retrospective study across five healthcare institutions on the Island of Montréal was undertaken. METHODS: We analyzed the genomes of 221 MABC isolates obtained from 115 individuals (2010-2018) to identify possible links. Genetic similarity, defined as ≤25 single-nucleotide polymorphisms (SNPs), was investigated through a blinded epidemiological inquiry. RESULTS: Bioinformatics analyses identified 28 sequence types (STs), including globally observed dominant circulating clones (DCCs). Further analysis revealed 210 isolate pairs within the SNP threshold. Among these pairs, there was one possible lab contamination where isolates from different patients processed in the same lab differed by only 2 SNPs. There were 37 isolate pairs from patients who had provided specimens from the same hospital; however, epidemiological analysis found no evidence of healthcare-associated person-to-person transmission between these patients. Additionally, pan-genome analysis showed higher discriminatory power than core genome analysis for examining genomic similarity. CONCLUSIONS: Genomics alone is insufficient to establish MABC transmission, particularly considering the genetic similarity and wide distribution of DCCs, although pan-genome analysis has the potential to add further insight. Our findings indicate that MABC infections in Montréal are unlikely attributable to healthcare-associated person-to-person transmission.

SARS-CoV-2 seroprevalence and mental health of school staff: a cross-sectional study of schools from four areas of Montreal, Quebec in 2021.

OBJECTIVES: To assess the seroprevalence of infection-acquired SARS-CoV-2 and the mental health of school/daycare staff in the months after reopening of schools in Montreal, Quebec (Canada) in the Fall of 2020 and whether these varied by school and participant characteristics. DESIGN: A cross-sectional design based on a convenience sample of schools/daycares and staff was used as the originally planned longitudinal design was no longer feasible due to obstacles in recruitment, for example, teacher's strike. SETTING: Forty-nine schools/daycares in four Montreal neighbourhoods from March to October 2021. PARTICIPANTS: Three-hundred and sixty-two participants completed both questionnaires and serology tests. PRIMARY AND SECONDARY OUTCOME MEASURES: SARS-CoV-2 seroprevalence and prevalence of anxiety, depression, resilience and burnout/emotional exhaustion. RESULTS: The seroprevalence estimate made representative to the Quebec population of educators was 8.6% (95% CI 5.2 to 13.0). The adjusted seroprevalence in high school was 20% that of elementary school (aRR=0.20, 95% CI 0.07 to 0.58). Thirty per cent of seropositive staff were exposed to a household member with confirmed COVID-19. Prevalence of high emotional exhaustion/burnout was 35%, 44% and 53% in daycare, elementary school and high school staff, respectively. However, moderate/severe anxiety and depression and low resilience did not exceed 18%. After adjusting for confounders, being very afraid of catching COVID-19 at school was associated with moderate-severe anxiety, moderate-severe depression and high emotional exhaustion (aRR=4.4, 95% CI 2.2 to 8.9; aRR=2.8, 95% CI 1.5 to 5.4; aRR=2.2, 95% CI 1.6 to 3.0, respectively). CONCLUSION: The seroprevalence, anxiety and depression among school/daycare staff were comparable to the reported levels in the adult population of Quebec. The prevalence of emotional exhaustion/burnout was high across all school levels and exceeding the average across all occupations in the USA and in teachers in Germany.

Evaluation of the decision-making process underlying the initial off-label use of vaccines: A scoping review.

BACKGROUND: This scoping review aimed to assess the non-standardized decision-making process of National or International Immunization Technical Advisory Groups (NITAG) in developing novel off-label recommendations by examining the supportive evidence. METHODS: We used the Joanna Briggs Institute framework. A search strategy was developed with a librarian to identify recommendations and evidence from peer-reviewed and gray literature until January 2022, using PubMed, Medline, EMBASE, clinicaltrials.gov, the International Clinical trials registry, governmental agency and pharmaceutical websites, the Global NITAG Network center website, and Google Scholar. Recommendations involving one of 26 pre-identified vaccine-preventable diseases, human use, and the introduction of a novel change across time and countries, were included. Evidence regarding efficacy/effectiveness, safety, or immunogenicity were included. Recommendations for fast-track approval, unlabeled or individual level off-label use, passive immunization, booster doses or provincial strategies were excluded. Only English and French documents were included. Two reviewers reviewed title/abstracts and full-text documents, and three performed data extraction. The primary outcome was the presence and elements of the evidence. FINDINGS: Out of 4023 documents, 12 were included, and 116 were found through manual search. Over the 40-year span captured (1982-2018), most recommendations were from the last two decades and included evidence, except three from the 1990s. Most included safety (69.2%) and immunogenicity (65.4%) studies and randomized controlled trials (57.7%). Indication-based recommendations included RCTs more often (84.6%) than posology-based recommendations (30.8%). There was evidence involving populations or vaccines different from those in the recommendation. INTERPRETATION: Critical outcomes evidence is not systematically included in off-label recommendations, nor must it involve the exact population or vaccine(s) of concern. However, in recent years, more off-label recommendations include critical outcome evidence, mainly RCTs.

Pandemic Stringency Measures and Hospital Admissions for Eating Disorders.

Importance: Hospitalizations for eating disorders rose dramatically during the COVID-19 pandemic. Public health restrictions, or stringency, are believed to have played a role in exacerbating eating disorders. Few studies of eating disorders during the pandemic have extended to the period when public health stringency restrictions were lifted. Objective: To assess the association between hospitalization rates for eating disorders and public health stringency during the COVID-19 pandemic and after the easing of public health restrictions. Design, Setting, and Participants: This Canadian population-based cross-sectional study was performed from April 1, 2016, to March 31, 2023, and was divided into pre-COVID-19 and COVID-19-prevalent periods. Data were provided by the Canadian Institute for Health Information and the Institut National d'Excellence en Santé et Services Sociaux for all Canadian provinces and territories. Participants included all children and adolescents aged 6 to 20 years. Exposure: The exposure was public health stringency, as measured by the Bank of Canada stringency index. Main Outcomes and Measures: The primary outcome was hospitalizations for a primary diagnosis of eating disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code F50), stratified by region, age group, and sex. Interrupted time series analyses based on Poisson regression were used to estimate the association between the stringency index and the rate of hospitalizations for eating disorders. Results: During the study period, there were 11 289 hospitalizations for eating disorders across Canada, of which 8726 hospitalizations (77%) were for females aged 12 to 17 years. Due to low case counts in other age-sex strata, the time series analysis was limited to females within the 12- to 17-year age range. Among females aged 12 to 17 years, a 10% increase in stringency was associated with a significant increase in hospitalization rates in Quebec (adjusted rate ratio [ARR], 1.05; 95% CI, 1.01-1.07), Ontario (ARR, 1.05; 95% CI, 1.03-1.07), the Prairies (ARR, 1.08; 95% CI, 1.03-1.13), and British Columbia (ARR, 1.11; 95% CI, 1.05-1.16). The excess COVID-19-prevalent period hospitalizations were highest at the 1-year mark, with increases in all regions: Quebec (RR, 2.17), Ontario (RR, 2.44), the Prairies (RR, 2.39), and British Columbia (RR, 2.02). Conclusion and Relevance: In this cross-sectional study of hospitalizations for eating disorders across Canada, hospitalization rates for eating disorders in females aged 12 to 17 years were associated with public health measure stringency. The findings suggest that future pandemic preparedness should consider implications for youths at risk for eating disorders and their resource and support needs.

Impact of antibiotic prophylaxis on urinary tract infection recurrence in children: Rapid review.

INTRODUCTION: Given the potential consequences associated with urinary tract infections (UTI), it has become standard practice to use continuous antibiotic prophylaxis (CAP) in children, even if controversial. We reviewed the effectiveness of CAP on recurrent UTI in a pediatric population to determine if equipoise remains and allow for a placebo control group to study the effectiveness of the vaccine MV140. METHOD: We completed a rapid review. We searched Medline, Embase and the Cochrane Library and data extraction was completed by a single reviewer. Our search criteria were 2005-2022, English and French language, randomized controlled trials (RCTs) and systematic reviews only. The population was 19 years and younger, including: vesicoureteral reflux (VUR), congenital anomalies of the kidneys and urinary tracts (CAKUT), and bladder and bowel dysfunction (BBD). RESULTS: Three RCTs and three systematic reviews found a benefit for CAP, mostly for a population with VUR, and those with severe VUR have more benefit. Most studies were not able to show a difference in the rate of UTIs or new renal scars (NRS). Three RCTs found a deleterious effect with CAP. Other studies were able to prove a benefit for patients with dilatation of the urinary tract without obstruction and high-grade VUR combined with BBD. The major adverse event found was antimicrobial resistance. CONCLUSIONS: High-risk patients benefit from CAP. The potential consequences of UTIs makes it unethical to use a placebo-only control group for them; however, CAP use seems difficult to justify in a low-risk population.

Mental Health Hospitalizations in Canadian Children, Adolescents, and Young Adults Over the COVID-19 Pandemic.

Importance: The COVID-19 pandemic resulted in multiple socially restrictive public health measures and reported negative mental health impacts in youths. Few studies have evaluated incidence rates by sex, region, and social determinants across an entire population. Objective: To estimate the incidence of hospitalizations for mental health conditions, stratified by sex, region, and social determinants, in children and adolescents (hereinafter referred to as youths) and young adults comparing the prepandemic and pandemic-prevalent periods. Design, Setting, and Participants: This Canadian population-based repeated ecological cross-sectional study used health administrative data, extending from April 1, 2016, to March 31, 2023. All youths and young adults from 6 to 20 years of age in each of the Canadian provinces and territories were included. Data were provided by the Canadian Institute for Health Information for all provinces except Quebec; the Institut National d'Excellence en Santé et en Services Sociaux provided aggregate data for Quebec. Exposures: The COVID-19-prevalent period, defined as April 1, 2020, to March 31, 2023. Main Outcomes and Measures: The main outcome measures were the prepandemic and COVID-19-prevalent incidence rates of hospitalizations for anxiety, mood disorders, eating disorders, schizophrenia or psychosis, personality disorders, substance-related disorders, and self-harm. Secondary measures included hospitalization differences by sex, age group, and deprivation as well as emergency department visits for the same mental health conditions. Results: Among Canadian youths and young adults during the study period, there were 218 101 hospitalizations for mental health conditions (ages 6 to 11 years: 5.8%, 12 to 17 years: 66.9%, and 18 to 20 years: 27.3%; 66.0% female). The rate of mental health hospitalizations decreased from 51.6 to 47.9 per 10 000 person-years between the prepandemic and COVID-19-prevalent years. However, the pandemic was associated with a rise in hospitalizations for anxiety (incidence rate ratio [IRR], 1.11; 95% CI, 1.08-1.14), personality disorders (IRR, 1.21; 95% CI, 1.16-1.25), suicide and self-harm (IRR, 1.10; 95% CI, 1.07-1.13), and eating disorders (IRR, 1.66; 95% CI, 1.60-1.73) in females and for eating disorders (IRR, 1.47; 95% CI, 1.31-1.67) in males. In both sexes, there was a decrease in hospitalizations for mood disorders (IRR, 0.84; 95% CI, 0.83-0.86), substance-related disorders (IRR, 0.83; 95% CI, 0.81-0.86), and other mental health disorders (IRR, 0.78; 95% CI, 0.76-0.79). Conclusions and Relevance: This cross-sectional study of Canadian youths and young adults found a rise in anxiety, personality disorders, and suicidality in females and a rise in eating disorders in both sexes in the COVID-19-prevalent period. These results suggest that in future pandemics, policymakers should support youths and young adults who are particularly vulnerable to deterioration in mental health conditions during public health restrictions, including eating disorders, anxiety, and suicidality.

Disinfection of sink drains to reduce a source of three opportunistic pathogens, during Serratia marcescens clusters in a neonatal intensive care unit.

OBJECTIVE: Evaluate the effects of five disinfection methods on bacterial concentrations in hospital sink drains, focusing on three opportunistic pathogens (OPs): Serratia marcescens, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. DESIGN: Over two years, three sampling campaigns were conducted in a neonatal intensive care unit (NICU). Samples from 19 sink drains were taken at three time points: before, during, and after disinfection. Bacterial concentration was measured using culture-based and flow cytometry methods. High-throughput short sequence typing was performed to identify the three OPs and assess S. marcescens persistence after disinfection at the genotypic level. SETTING: This study was conducted in a pediatric hospitals NICU in Montréal, Canada, which is divided in an intensive and intermediate care side, with individual rooms equipped with a sink. INTERVENTIONS: Five treatments were compared: self-disinfecting drains, chlorine disinfection, boiling water disinfection, hot tap water flushing, and steam disinfection. RESULTS: This study highlights significant differences in the effectiveness of disinfection methods. Chlorine treatment proved ineffective in reducing bacterial concentration, including the three OPs. In contrast, all other drain interventions resulted in an immediate reduction in culturable bacteria (4-8 log) and intact cells (2-3 log). Thermal methods, particularly boiling water and steam treatments, exhibited superior effectiveness in reducing bacterial loads, including OPs. However, in drains with well-established bacterial biofilms, clonal strains of S. marcescens recolonized the drains after heat treatments. CONCLUSIONS: Our study supports thermal disinfection (>80°C) for pathogen reduction in drains but highlights the need for additional trials and the implementation of specific measures to limit biofilm formation.

Revaccination outcomes among adolescents and adults with suspected hypersensitivity reactions following COVID-19 vaccination: A Canadian immunization research network study.

BACKGROUND: COVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations. METHODS: Individuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied. RESULTS: The analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis. All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms. CONCLUSIONS: Most individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination.

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.

Antenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization and risk of serogroup 19 IPD in children: An indirect cohort study.

The tetanus-diphtheria-acellular pertussis (Tdap) vaccine has been indicated for pregnant women in Quebec, Canada since 2018. Recent literature suggests maternal Tdap interferes with the pneumococcal vaccine response in children exposed in utero because of maternally transferred anti-diphtheria antibodies, a phenomenon known as blunting. Using an indirect cohort study, we investigated whether maternal Tdap vaccination could alter the protection of PCV vaccines against serotype 19A/F IPD (conjugated to diphtheria toxoid in PCV10). Thirty-seven immunized IPD cases (serotype 19A/F) and 90 immunized IPD controls (non-vaccine serotypes) were analyzed using multivariate logistic regression. Our analyses did not identify antenatal Tdap exposure as a risk factor for IPD in vaccinated children, with and odds ratio close to the null (odds ratio = 0.82, 95%CI = 0.32-2.07). As this study is the first to assess the impact of maternal immunization on pneumococcal disease risk, future investigations involving a larger number of cases should be conducted to confirm or infirm our findings.

Comparison of Omicron breakthrough infection versus monovalent SARS-CoV-2 intramuscular booster reveals differences in mucosal and systemic humoral immunity.

Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two-dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT. Our results show thatBT infection induces cell-mediated immune responses to variants comparable to an intramuscular vaccine booster dose. In contrast, BT subjects had higher salivary immunoglobulin (Ig)G and IgA levels against the Omicron spike and enhanced reactivity to the ancestral spike for the IgA isotype, which also reacted with SARS-CoV-1. Serumneutralizing antibody levels against the ancestral strain and the variants were also higher after BT infection. Our results support the need for the development of intranasal vaccines that could emulate the enhanced mucosal and humoral immunity induced by Omicron BT without exposing individuals to the risks associated with SARS-CoV-2 infection.

Multisystem inflammatory syndrome in 1.2 million children: longitudinal cohort study of risk factors.

BACKGROUND: We identified patient characteristics associated with an increased risk of developing MIS-C. METHODS: We conducted a longitudinal cohort study of 1,195,327 patients aged 0-19 years between 2006 and 2021, including the first two waves of the pandemic (February 25-August 22, 2020 and August 23, 2020-March 31, 2021). Exposures included prepandemic morbidity, birth outcomes, and family history of maternal disorders. Outcomes included MIS-C, Kawasaki disease, and other Covid-19 complications during the pandemic. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between patient exposures and these outcomes using log-binomial regression models adjusted for potential confounders. RESULTS: Among 1,195,327 children, 84 developed MIS-C, 107 Kawasaki disease, and 330 other Covid-19 complications during the first year of the pandemic. Prepandemic hospitalizations for metabolic disorders (RR 11.3, 95% CI 5.61-22.6), atopic conditions (RR 3.34, 95% CI 1.60-6.97), and cancer (RR 8.11, 95% CI 1.13-58.3) were strongly associated with the risk of MIS-C, compared with no exposure. These same exposures were also associated with Kawasaki disease and other Covid-19 complications. However, birth characteristics and history of maternal morbidity were not associated with MIS-C development. CONCLUSIONS: Children with pre-existing morbidity have a considerably elevated risk of MIS-C. IMPACT: Morbidities that predispose children to multisystem inflammatory syndrome (MIS-C) are unclear. In this study, prepandemic hospitalizations for metabolic disorders, atopic conditions, and cancer were associated with an elevated risk of MIS-C. Birth characteristics and family history of maternal morbidity were not, however, associated with MIS-C. Pediatric morbidities may play a greater role in MIS-C onset than maternal or perinatal characteristics, and may help clinicians better recognize children at risk for this complication.

Canada's National Advisory Committee on immunization: Adaptations and challenges during the COVID-19 pandemic.

The COVID-19 pandemic has challenged traditional vaccine guidance infrastructure and frameworks, and added urgency and complexity to the operation of National Immunization Technical Advisory Groups (NITAGs). Canada's National Advisory Committee on Immunization (NACI) provides immunization guidance to the Public Health Agency of Canada (PHAC) who publicly shares expert and evidence-informed guidance with Canadian provinces and territories. Throughout the pandemic, NACI and PHAC implemented many adaptations to meet urgent needs for pandemic vaccine guidance. In this paper, we describe: structural adaptations in response to the accelerated pace and amount of work required to issue recommendations that were timed around product authorizations and dynamic epidemiology; technical adaptations in response to rapidly evolving evidence of variable quality which required close monitoring, and which promoted reliance on basic vaccine principles due to incomplete direct evidence; the need to provide nimble advice (e.g., off-label recommendations, preferential recommendations); communications adaptations (e.g. identify sustainable spokespeople for the committee, receive stakeholder feedback, and ensure urgent nuanced advice was communicated to a diverse audience); and research adaptations focussing on solutions to constrained supply (e.g. prioritisation, extended intervals, and heterologous schedules). The early pandemic vaccine experience has created a roadmap of lessons and adaptations that should be leveraged in future pandemic vaccine programs, and has highlighted the essential role of NITAGs to complement regulatory structures during pandemics to ensure timely, impactful, and evidence-informed public health vaccine guidance.

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.

Clonal diversity of Streptococcus pneumoniae serotype 19A collected from children < 5 years old in Québec, Canada, 2016-2021.

Streptococcus pneumoniae serotype 19A is a highly diverse, often antimicrobial-resistant Gram-positive bacterium which can cause invasive pneumococcal disease (IPD). In 2021, public health authorities in the Canadian province of Québec observed an increase of serotype 19A IPD in children <5 years. The purpose of this study was to determine the clonal composition of serotype 19A isolates collected from this age group in Québec, from 2016 to 2021. Forty-one and 37 IPD isolates from children <5 years from Québec and the remainder of Canada, respectively, were sequenced using the Illumina NextSeq platform. Phylogenetic analysis using SNVPhyl identified three clusters, corresponding to three common clones of serotype 19A: CC199, CC320 and ST695. CC199, predominantly represented by ST416, accounted for similar proportions of serotype 19A isolates collected from children in Québec (19.5 %) and other Canadian jurisdictions (OCJs, 21.6 %), with significant presence of ermB (62.5 % and 60 % of ST416 isolates, respectively). CC320 was more commonly identified from OCJs in comparison to Québec (18.9 % vs. 7.3 %, respectively), but were highly antimicrobial-resistant regardless of region. ST695 was the most common clone of serotype 19A collected in Québec from children <5 years, representing 65.9 % of isolates collected over the study period (40.5 % of isolates collected in OCJs). Phylogenetic analysis identified geographical differences in ST695 across Canada; including a large clade specific to Québec (with both susceptible and macrolide-resistant [ermB] subclades), and a separate macrolide-resistant (mefA) clade associated with OCJs. The Québec-specific ermB-ST695 clone represented 48.1 % of ST695 collected from the province. Continued genomic surveillance of S. pneumoniae serotype 19A is required to: i) track the prevalence and clonal composition of serotype 19A in Québec in future years; ii) characterize the clonal distribution of serotype 19A in adult populations; and iii) monitor whether the currently geographically restricted ermB-ST695 clone observed in Québec expands to OCJs.

Infection-induced seroconversion and seroprevalence of SARS-CoV-2 among a cohort of children and youth in Montreal, Canada.

The EnCORE study is a prospective serology study of SARS-CoV-2 in a cohort of children from Montreal, Canada. Based on data from our fourth round of data collection (May-October 2022), we estimated SARS-CoV-2 seroprevalence and seroconversion. Using multivariable regression, we identified factors associated with seroconversion. Our results show that previously seronegative children were approximately 9-12 times more likely to seroconvert during the early Omicron-dominant period compared to pre-Omicron rounds. Unlike the pre-Omicron rounds, the adjusted rate of seroconversion among 2- to 4-year-olds was higher than older age groups. As seen previously, higher seroconversion rates were associated with ethnic/racial minority status.