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Background: Influenza vaccines are crucial in reducing the risk of influenza symptoms. We aimed to: (1) estimate the association between public health unit (PHU) funding per capita and influenza vaccination among individuals aged 12 and older in Ontario in 2013/2014 and 2018/2019 and (2) determine whether any observed associations were heterogeneous across household income groups, gender and age categories., Methods: Cross-sectional studies were conducted using the Canadian Community Health Survey, a population-representative survey that collects annual health data. PHU funding per capita was measured using the approved provincial funding for mandatory programmes and the Canadian Census Population Estimates. Self-reported influenza vaccination status in the past year was used. Multilevel logistic regression was used to estimate the association., Results: A case-complete weighted dataset revealed that 33.2% in 2013/2014 and 35.1% in 2018/2019 of respondents were vaccinated. In 2013/2014, every standard deviation (SD) increase in PHU funding per capita was associated with vaccination (OR: 1.08; 95% CI: 1.01, 1.15; SD: 14.1). Furthermore, for every SD increase in PHU funding per capita in 2013/2014, individuals from the lowest household income and between the ages of 50 and 64 years were 29% (95% CI: 1.10, 1.50) and 13% (95% CI: 1.03, 1.23) more likely to be vaccinated, respectively, while adjusting for confounders. No heterogeneous associations were observed in 2018/2019., Conclusion: Funding may have the potential to support PHU's role in preventing diseases, promoting health and reducing health inequities among the population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transitions to endemicity and respiratory syncytial virus (RSV) and influenza reestablish their seasonal circulation patterns, understanding their comparative burden on infants and children can guide health system responses and funding priorities., Methods: This was a population-based cohort study of children aged <5 years in Ontario, Canada, from September 2018 to August 2023 using linked health administrative databases., Results: Seasonal cohorts comprised 731 838 to 763 660 children. RSV- and influenza-related hospital admission rates immediately decreased in March 2020. In 2021-2022, RSV-related admissions rebounded but remained 8%-11% lower than prepandemic seasons, whereas 2022-2023 RSV-related admissions increased 105%-113% versus prepandemic seasons and peak admissions occurred in November versus December. Influenza did not rebound until 2022-2023, when admissions were 28%-37% higher than prepandemic seasons. Coronavirus disease 2019 (COVID-19)-related admissions remained low until 2021-2022 and were lower than RSV-related admissions across all age groups during prepandemic and pandemic seasons. By contrast, 2021-2022 COVID-19-related admissions exceeded prepandemic influenza-related admissions by 30%-40% but decreased by 45% in 2022-2023 and were lower than prepandemic influenza-related admissions, except among infants aged <12 months who remained at highest risk. There was no distinct seasonal pattern for COVID-19-related admissions during the study., Conclusions: RSV remains a major cause of childhood hospitalization. Although COVID-19 appears to be receding, its disease burden as it transitions to endemicity remains to be established. The unprecedented peaks in RSV-related hospital admissions during 2022-2023, together with the return of influenza and ongoing SARS-CoV-2 transmission, underscore the need to strengthen systems for real-time surveillance and to proactively prepare for critical healthcare scenarios., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

BackgroundLate outbreak identification is a common risk factor mentioned in case reports of large respiratory infection outbreaks in long-term care (LTC) homes.AimTo systematically measure the association between late SARS-CoV-2 outbreak identification and secondary SARS-CoV-2 infection and mortality in residents of LTC homes.MethodsWe studied SARS-CoV-2 outbreaks across LTC homes in Ontario, Canada from March to November 2020, before the COVID-19 vaccine rollout. Our exposure (late outbreak identification) was based on cumulative infection pressure (the number of infectious resident-days) on the outbreak identification date (early: ≤ 2 infectious resident-days, late: ≥ 3 infectious resident-days), where the infectious window was -2 to +8 days around onset. Our outcome consisted of 30-day incidence of secondary infection and mortality, based on the proportion of at-risk residents with a laboratory-confirmed SARS-CoV-2 infection with onset within 30 days of the outbreak identification date.ResultsWe identified 632 SARS-CoV-2 outbreaks across 623 LTC homes. Of these, 36.4% (230/632) outbreaks were identified late. Outbreaks identified late had more secondary infections (10.3%; 4,437/42,953) and higher mortality (3.2%; 1,374/42,953) compared with outbreaks identified early (infections: 3.3%; 2,015/61,714; p < 0.001, mortality: 0.9%; 579/61,714; p < 0.001). After adjustment for 12 LTC home covariates, the incidence of secondary infections in outbreaks identified late was 2.90-fold larger than that of outbreaks identified early (OR: 2.90; 95% CI: 2.04-4.13).ConclusionsThe timeliness of outbreak identification could be used to predict the trajectory of an outbreak, plan outbreak measures and retrospectively provide feedback for quality improvement, with the objective of reducing the impacts of respiratory infections in LTC home residents.

Objective: To estimate the real world effectiveness of modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine against mpox infection., Design: Emulation of a target trial., Setting: Linked databases in Ontario, Canada., Participants: 9803 men aged ≥18 years with a history of being tested for syphilis and a laboratory confirmed bacterial sexually transmitted infection (STI) in the previous year, or who filled a prescription for HIV pre-exposure prophylaxis in the previous year. On each day between 12 June 2022 and 27 October 2022, those who had been vaccinated 15 days previously were matched 1:1 with unvaccinated men by age, geographical region, past HIV diagnosis, number of bacterial STI diagnoses in the previous three years, and receipt of any non-MVA-BN vaccine in the previous year., Main Outcome Measure: The main outcome measure was vaccine effectiveness ((1-hazard ratio)×100) of one dose of subcutaneously administered MVA-BN against laboratory confirmed mpox infection. A Cox proportional hazards model was used to estimate hazard ratios to compare the rate of laboratory confirmed mpox between the two groups., Results: 3204 men who received the vaccine were matched to 3204 unvaccinated controls. A total of 71 mpox infections were diagnosed, with 0.09 per 1000 person days (95% confidence interval (CI) 0.05 to 0.13) in the vaccinated group and 0.20 per 1000 person days (0.15 to 0.27) in the unvaccinated group over the study period of 153 days. Estimated vaccine effectiveness of one dose of MVA-BN against mpox infection was 58% (95% CI 31% to 75%)., Conclusion: The findings of this study, conducted in the context of a targeted vaccination programme and evolving outbreak of mpox, suggest that one dose of MVA-BN is moderately effective in preventing mpox infection., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from ICES and the Canadian Immunization Research Network; no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Respiratory syncytial virus (RSV) vaccines could reduce disease burden and costs in older Canadian adults, but vaccination program cost-effectiveness is unknown. We evaluated the cost-effectiveness of different age cut-offs for RSV adult vaccination programs, with or without a focus on people with higher disease risk due to chronic medical conditions., Methods: We developed a static individual-based model of medically attended RSV disease to compare alternative age-, medical risk-, and age-plus medical risk-based vaccination policies. The model followed a multiage population of 100 000 people aged 50 years and older. Vaccine characteristics were based on RSV vaccines authorized in Canada as of May 2024, with vaccine protection assumed to last 2 years (or 3 years in scenario analyses). We calculated sequential incremental cost-effectiveness ratios in 2023 Canadian dollars per quality-adjusted life year (QALY) from the health-system and societal perspectives, discounted at 1.5%., Results: Although all vaccination strategies averted medically attended RSV disease, universal age-based strategies were not an efficient use of resources compared with medical risk-based strategies. Vaccinating adults aged 70 years and older with 1 or more chronic medical condition was the optimal strategy for a cost-effectiveness threshold of $50 000 per QALY. Results were sensitive to assumptions about vaccine price, but medical risk-based approaches remained optimal compared with age-based strategies, even when vaccine prices were low. Findings were robust to a range of alternative assumptions., Interpretation: Vaccination programs for RSV in some groups of older Canadians with underlying medical conditions are likely cost-effective. These findings can inform the design of vaccination programs., Competing Interests: Competing interests:: Sarah Buchan declares funds from the Canadian Institutes of Health Research and SickKids to support work on the burden of respiratory syncytial virus (RSV) in older adults and young children. Dr. Buchan is a member of the National Advisory Committee on Immunization (NACI) RSV Working Group and liaison member to NACI for the Canadian Association for Immunization Research, Evaluation and Education. Nicholas Brousseau is a member of NACI and the Quebec Immunization Committee. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Introduction: The incidence of varicella in Canada has decreased by almost 99% since vaccination was introduced. However, variation in the timing and eligibility of vaccination programs across the country has resulted in some cohorts being under-vaccinated and therefore potentially susceptible to infection., Methods: We used nationally representative specimens from the Biobank of Statistics Canada's Canadian Health Measures Survey (CHMS) as well as residual specimens from Ontario collected between 2009-2014 to estimate population immunity across age-groups and geography, and identify any groups at increased risk of varicella infection., Results: The weighted proportion of specimens with antibody levels above the threshold of protection was 93.6% (95% CI: 92.4, 95.0). Protection was lowest among those aged 3-5 years (54.3%; 95% CI: 47.3, 61.4), but increased with age. Individuals born outside Canada had more than twice the odds of varicella susceptibility than those born in Canada (aOR: 2.7; 95% CI: 1.4, 5.0; p = 0.004). There were no differences by sex or geography within Canada, and there were no statistically significant differences when Ontario CHMS sera were compared to Ontario residual sera, apart from in participants aged 12-19 year age-group, for whom the CHMS estimate (91.2%; 95% CI: 86.7, 95.7) was significantly higher (p = 0.03) than that from residual specimens (85.9%, 95% CI: 81.1, 90.8)., Discussion: Varicella immunity in Canada is changing. Children appear to have low population immunity, placing them at greater risk of infection and at increased risk of severe disease as they age. Our results underscore the importance of performing periodic serosurveys to monitor further population immunity changes as the proportion of vaccine-eligible birth-cohorts increases, and to continually assess the risk of outbreaks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wright et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We found that rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and reverse transcriptase (RT)-PCR-confirmed infection were approximately 50% higher in a population-based cohort of people with HIV compared with a matched cohort of people without HIV during the Omicron era (2 January 2022 to 31 March 2023) in Ontario, Canada, after controlling for age, sex, residential census tract, and country of birth. Rates of coronavirus disease 2019 (COVID-19)-related hospitalization and/or death were more than double. Differences persisted independent of vaccination, healthcare access, and COVID-19 diagnosis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited., Methods: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010 to 2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders., Results: Among 23 806 infants tested for influenza, 1783 (7.5%) were positive and 1708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI], 50%-74%). VE was similar by trimester of vaccination (first/second, 66% [95% CI, 40%-80%]; third, 63% [95% CI, 46%-74%]), infant age at testing (0 to <2 months, 63% [95% CI, 46%-75%]; 2 to <6 months, 64% [95% CI, 36%-79%]), and gestational age at birth (≥37 weeks, 64% [95% CI, 50%-75%]; < 37 weeks, 61% [95% CI, 4%-86%]). VE against influenza hospitalization was 67% (95% CI, 50%-78%)., Conclusions: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available., Competing Interests: Potential conflicts of interest . During the conduct of this work, D. B. F. worked for the University of Ottawa and had academic appointments at the Children's Hospital of Eastern Ontario Research Institute and ICES; she is currently employed by Pfizer. K. W. is a cofounder and Chief Scientific Officer of CANImmunize, Inc; he served on the Independent Data Monitoring Committee for Medicago; and is a member of the Moderna Global Advisory Core Consultancy Group. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Beyond clinical risk factors, little is known about the impact of social determinants on respiratory syncytial virus (RSV) burden. Our study aimed to estimate RSV-related hospitalization rates across sociodemographic and housing characteristics., Methods: We conducted a population-based study of all RSV-related hospitalizations in Ontario, Canada, between September 1, 2016, and August 31, 2019, using validated hospital discharge codes and census data. Crude and age-standardized annualized RSV incidence rates and rate ratios (RRs) were estimated for a range of individual-level demographics and neighborhood-level measures of marginalization and housing characteristics., Results: Overall, the annual RSV-related hospitalization rate was 27 per 100 000, with the highest rates observed in children age <12 months (1049 per 100 000) and 12-23 months (294 per 100 000) and adults age ≥85 years (155 per 100 000). Higher RSV-related hospitalization rates were associated with increasing marginalization quintile (Q) of material resources (RR, 1.4; Q5: 33 per 100 000 vs Q1: 24 per 100 000) and household instability (RR, 1.5; Q5: 31 per 100 000 vs Q1: 22 per 100 000)., Conclusions: The burden of RSV-related hospitalization was greatest in young children and older adults, with variation by sociodemographic and housing factors. Understanding the role of these social factors is crucial for informing equitable preventive program delivery., Competing Interests: Potential conflicts of interest. The authors do not have a commercial or other association that might pose a conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Respiratory syncytial virus (RSV) transmission was disrupted worldwide following the COVID-19 pandemic, and further study is required to better understand these changes., Objective: To compare observed and expected RSV hospital and intensive care unit (ICU) admission rates and characteristics of admitted children during the 2021-2022 and 2022-2023 seasons., Design, Setting, and Participants: A population-based cohort study of all children aged younger than 5 years in Ontario, Canada, July 1, 2017, through March 31, 2023, was conducted., Exposures: Individual and neighborhood-level sociodemographic and clinical characteristics were identified from administrative data, including age, palivizumab eligibility, complex medical conditions, rurality, and living in a marginalized neighborhood., Main Outcomes and Measures: The main outcome was RSV-associated hospitalization. Secondary outcomes included ICU admissions, mechanical ventilation, extracorporeal membrane oxygenation, and in-hospital death. Poisson generalized estimating equations were used to model weekly age- and sex-specific hospitalization rates and estimate expected rates in the postpandemic era; adjusted rate ratios (RRs) and 95% CIs are reported., Results: This cohort study included approximately 700 000 children per study year. Compared with prepandemic years (2017-2018, 2018-2019, and 2019-2020), the 2021-2022 RSV season peaked slightly earlier, but overall admission rates were comparable (289.1 vs 281.4-334.6 per 100 000, or approximately 2000 admissions). The 2022-2023 season peaked a month earlier and resulted in more than twice as many hospitalizations (770.0 per 100 000; n = 4977 admissions). The proportion of children admitted to an ICU in 2022-2023 (13.9%) was slightly higher than prepandemic (9.6%-11.4%); however, the population-based rate was triple the prepandemic levels (106.9 vs 27.6-36.6 per 100 000 children in Ontario). With the exception of palivizumab-eligible children, all sociodemographic and health status characteristics were associated with lower-than-expected RSV hospitalization rates in 2021-2022. In contrast, older age of patients was associated with higher-than-expected rates in 2022-2023 (ie, 24-59 months: RR, 1.90; 95% CI, 1.35-2.66)., Conclusions and Relevance: There were notable differences in RSV epidemiologic characteristics in Ontario following the COVID-19 pandemic. It is not yet clear whether and how long atypical RSV epidemics may persist. Clinicians and program planners should consider the potential for ongoing impacts to health care capacity and RSV immunization programs.

Background: New vaccine products were recently authorized for protection against invasive pneumococcal disease (IPD) in Canada. Our aim was to determine age- and serotype-specific trends in IPD incidence and severity in Canada's largest province, Ontario., Methods: We included all confirmed IPD cases reported in Ontario and defined the pre-pneumococcal 13-valent conjugate vaccine (PCV13) era (01/2007 to 12/2010), post-PCV13 era (01/2011 to 12/2019), and coronavirus disease 2019 (COVID-19) pandemic era (01/2020 to 12/2022). We estimated incidence, hospitalization, and case fatality rate (CFR) by age. We grouped IPD cases by vaccine-specific serotypes (PCV13; PCV15-non-PCV13; PCV20-non-PCV13; PCV20-non-PCV15; polysaccharide 23-valent vaccine-non-PCV20; and non-vaccine-preventable [NVP]). We then compared incidence rates by age and serotype group in the pre- and post-PCV13 eras by calculating rate ratios (RRs) and their 95% CIs., Results: Incidence and hospitalizations declined from the pre- to post-PCV13 era in children aged <5 years (RR, 0.7; 95% CI, 0.6-0.8; and RR, 0.8; 95% CI, 0.7-0.9, respectively), but the CFR increased (1.4% to 2.3%). Other age groups saw smaller declines or more stable incidence rates across the years; hospitalizations increased in adults aged 50-64 years (RR, 1.2; 95% CI, 1.1-1.4) and ≥65 years (RR, 1.1; 95% CI, 1.0-1.1). For all ages, IPD cases and hospitalizations attributable to PCV13 serotypes declined, and those attributable to PCV15-non-PCV13, PCV20-non-PCV13, and NVP serotypes increased. IPD incidence declined during the COVID-19 era., Conclusions: IPD incidence and hospitalizations due to PCV13 serotypes decreased after PCV13 introduction but increased for other serotypes. Continued surveillance is required to evaluate changes to pneumococcal vaccination programs and ongoing changes to the distribution of IPD-causing serotypes., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: We assessed protection from coronavirus disease 2019 (COVID-19) vaccines and/or prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection against Omicron-associated severe outcomes during successive sublineage-predominant periods., Methods: We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, polymerase chain reaction (PCR)-tested adults aged ≥50 years in Ontario, Canada, between 2 January 2022 and 30 June 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection., Results: We included 18 526 cases with Omicron-associated severe outcomes and 90 778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95% confidence interval [CI] 63%-72%; fourth-dose, 6-month: 80%, 95% CI 77%-83%) but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95% CI 48%-67%; 12-month: 49%, 95% CI 41%-56%; fourth-dose, 6-month: 62%, 95% CI 56%-68%, 12-months: 51%, 95% CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95% CI 36%-75%; fourth-dose, 6-month: 63%, 95% CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95% CI 79%-96%). Prior infection alone did not confer lasting protection., Conclusions: Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review., Competing Interests: Potential conflicts of interest. N. L. has previously received honoraria for consultancy work, speaking in educational programs, and/or travel support from: Shionogi Inc., Gilead Sciences Canada Inc., Janssen Inc., GlaxoSmithKline plc., Sanofi Pasteur Ltd., F. Hoffmann-La Roche Ltd., Genentech Inc., CIDARA Therapeutics Inc., Clarion Healthcare, bioStrategies, Technospert, Aligos; all unrelated to this work. K. W. is a shareholder and board member and Co-founder and Chief Scientific Officer of CANImmunize Inc. and has served on independent scientific advisory boards for Medicago (Independent Data Monitoring Committee) and Moderna (Global Advisory Core Consultancy Group). J. G. reports a position as a paid consultant scientific editor for GIDEON Informatics, Inc., which is unrelated to the current work. S. E. W. reports being a co-investigator on a grant related to public health surveillance of invasive pneumococcal disease (no involvement in administration of funds) for the Canadian Immunization Research Network and a co-investigator on a grant on immunization data in Canada (no involvement in administration of funds) for CIRN; travel support to attend the Future of Vaccinology conference in October 2023 as an invited speaker from McMaster University (Hamilton, ON) and a role as an unpaid volunteer member for Canada's National Advisory Committee on Immunization (NACI). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To compare myocarditis/pericarditis risk after COVID-19 mRNA vaccination versus SARS-CoV-2 infection, and to assess if myocarditis/pericarditis risk varies by vaccine dosing interval., Methods: In this retrospective cohort study, we used linked databases in Quebec, Ontario, and British Columbia between January 26, 2020, and September 9, 2021. We included individuals aged 12 or above who received an mRNA vaccine as the second dose or were SARS-CoV-2-positive by RT-PCR. The outcome was hospitalization/emergency department visit for myocarditis/pericarditis within 21 days of exposure. We calculated age- and sex-stratified incidence ratios (IRs) of myocarditis/pericarditis following mRNA vaccination versus SARS-CoV-2 infection. We also calculated myocarditis/pericarditis incidence by vaccine type, homologous/heterologous schedule, and dosing interval. We pooled province-specific estimates using meta-analysis., Results: Following 18,860,817 mRNA vaccinations and 860,335 SARS-CoV-2 infections, we observed 686 and 160 myocarditis/pericarditis cases, respectively. Myocarditis/pericarditis incidence was lower after vaccination than infection (IR [BNT162b2/SARS-CoV-2], 0.14; 95%CI, 0.07-0.29; IR [mRNA-1273/SARS-CoV-2], 0.28; 95%CI, 0.20-0.39). Within the vaccinated cohort, myocarditis/pericarditis incidence was lower with longer dosing intervals; IR (56 or more days/15-30 days) was 0.28 (95%CI, 0.19-0.41) for BNT162b2 and 0.26 (95%CI, 0.18-0.38) for mRNA-1273., Conclusion: Myocarditis/pericarditis risk was lower after mRNA vaccination than SARS-CoV-2 infection, and with longer intervals between primary vaccine doses., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Naveed Z. Janjua reports a relationship with 10.13039/100006483AbbVie Inc that includes: consulting or advisory and speaking and lecture fees. Naveed Z. Janjua reports a relationship with 10.13039/100005564Gilead Sciences that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024 Published by Elsevier Ltd.)

We estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged ≥50 years in Ontario, Canada. Monovalent and bivalent mRNA COVID-19 booster doses provided similar strong initial protection against severe outcomes. Uncertainty remains around waning of protection from these vaccines., Competing Interests: Potential conflicts of interest . K. W. is a shareholder and board member of CANImmunize Inc and has served on independent scientific advisory boards for Medicago and Moderna. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aOR per 28 days  = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aOR per 28 days  = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Objectives: The objectives of this study are to determine the prevalence of influenza vaccine uptake across Canadians aged 18 to 64 years with different sense of community belonging (SoCB) and whether SoCB is associated with uptake of the seasonal influenza vaccine., Methods: We combined the 2007 to 2014 cycles of the nationally representative Canadian Community Health Survey (N = 301,802). The main exposure, SoCB, was measured as "strong" vs "weak." The outcome of interest was receipt of the influenza vaccine within the preceding 12 months. We used robust Poisson regression to estimate prevalence ratios. Normalized weights were utilized to account for the unequal probability of sample selection., Results: The adjusted prevalence of uptake of seasonal influenza vaccines was modestly greater for individuals with a strong SoCB compared to those with a weak SoCB (PR, 1.12; 95% CI, 1.11, 1.13). Older individuals, females, those with post-secondary education, non-immigrants, those who are married, those with at least one chronic condition, and those residing in a jurisdiction where pharmacists are authorized to administer influenza vaccine and/or where influenza vaccine is universally funded for all residents were more likely to have received an influenza vaccine within the past year., Conclusion: Canadians with a strong SoCB had modestly higher uptake of seasonal influenza vaccines. While the association is modest, findings suggest that SoCB may be an important component to investigate further and to consider in efforts aimed to increase the uptake of seasonal influenza vaccines., (© 2023. The Author(s) under exclusive license to The Canadian Public Health Association.)

Timely and precise influenza vaccine effectiveness (VE) estimates are needed to guide public health messaging and impact vaccine uptake immediately. Using routinely collected laboratory, vaccination and health administrative data from Alberta, Canada, we estimated influenza VE against infection for the 2023/24 season on a near real-time basis, to late December, at 61% (95% CI: 58-64) against influenza A(H1N1), 49% (95% CI: 28-63) against influenza A(H3N2) and 75% (95% CI: 58-85) against influenza B.

Importance: The study team previously showed that maternal mRNA COVID-19 vaccination during pregnancy confers protection against SARS-CoV-2 infection and COVID-19-related hospital admission in newborns and young infants. In this study, the study team evaluated newborn and early infant safety outcomes following maternal messenger RNA (mRNA) COVID-19 vaccination during pregnancy, for which there is limited comparative epidemiological evidence., Objective: To determine if maternal mRNA COVID-19 vaccination during pregnancy is associated with adverse newborn and early infant outcomes., Design, Setting, and Participants: This population-based retrospective cohort study took place in Ontario, Canada, using multiple linked health administrative databases. Singleton live births with an expected delivery date between May 1, 2021, and September 2, 2022, were included. Data were analyzed from January 2023 through March 2023., Exposure: Maternal mRNA COVID-19 vaccination (1 or more doses) during pregnancy., Main Outcomes and Measures: Severe neonatal morbidity (SNM), neonatal death, neonatal intensive care unit (NICU) admission, neonatal readmission, and hospital admission up to 6 months of age. The study team calculated inverse probability of treatment weighted risk ratios (RRs) and fit weighted Cox proportional hazards regression models comparing outcomes in infants of mothers who received COVID-19 vaccination during pregnancy with those who received no COVID-19 vaccine doses before delivery., Results: In total, 142 006 infants (72 595 male [51%]; mean [SD] gestational age at birth, 38.7 [1.7] weeks) were included; 85 670 were exposed to 1 or more COVID-19 vaccine doses in utero (60%). Infants of vaccinated mothers had lower risks of SNM (vaccine exposed 7.3% vs vaccine unexposed 8.3%; adjusted RR [aRR], 0.86; 95% CI, 0.83-0.90), neonatal death (0.09% vs 0.16%; aRR, 0.47; 95% CI, 0.33-0.65), and NICU admission (11.4% vs 13.1%; aRR, 0.86; 95% CI, 0.83-0.89). There was no association between maternal vaccination during pregnancy and neonatal readmission (5.5% vs 5.1%; adjusted hazard ratio, 1.03; 95% CI, 0.98-1.09) or 6-month hospital admission (8.4% vs 8.1%; adjusted hazard ratio, 1.01; 95% CI, 0.96-1.05)., Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, maternal mRNA COVID-19 vaccination during pregnancy was associated with lower risks of SNM, neonatal death, and NICU admission. In addition, neonatal and 6-month readmissions were not increased in infants of mothers vaccinated during pregnancy.

During the rapid deployment of COVID-19 vaccines in 2021, safety concerns may have led some pregnant individuals to postpone vaccination until after giving birth. This study aimed to describe temporal patterns and factors associated with COVID-19 vaccine series initiation after recent pregnancy in Ontario, Canada. Using the provincial birth registry linked with the COVID-19 vaccine database, we identified all individuals who gave birth between January 1 and December 31, 2021, and had not yet been vaccinated by the end of pregnancy, and followed them to June 30, 2022 (follow-up ranged from 6 to 18 months). We used cumulative incidence curves to describe COVID-19 vaccine initiation after pregnancy and assessed associations with sociodemographic, pregnancy-related, and health behavioral factors using Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Among 137,198 individuals who gave birth in 2021, 87,376 (63.7%) remained unvaccinated at the end of pregnancy; of these, 65.0% initiated COVID-19 vaccination by June 30, 2022. Lower maternal age (<25 vs. 30-34 y aHR: 0.73, 95%CI: 0.70-0.77), smoking during pregnancy (vs. nonsmoking aHR: 0.68, 95%CI: 0.65-0.72), lower neighborhood income (lowest quintile vs. highest aHR: 0.79, 95%CI: 0.76-0.83), higher material deprivation (highest quintile vs. lowest aHR: 0.74, 95%CI: 0.70-0.79), and exclusive breastfeeding (vs. other feeding aHR: 0.81, 95%CI: 0.79-0.84) were associated with lower likelihood of vaccine initiation. Among unvaccinated individuals who gave birth in 2021, COVID-19 vaccine initiation after pregnancy reached 65% by June 30, 2022, suggesting persistent issues with vaccine hesitancy and/or access to vaccination in this population.

Background: Respiratory syncytial virus (RSV) contributes significantly to morbidity in children, placing substantial burdens on health systems, thus RSV vaccine development and program implementation are a public health priority. More data on burden are needed by policymakers to identify priority populations and formulate prevention strategies as vaccines are developed and licensed., Methods: Using health administrative data, we calculated incidence rates of RSV hospitalization in a population-based birth cohort of all children born over a six-year period (May 2009 to June 2015) in Ontario, Canada. Children were followed until their first RSV hospitalization, death, 5th birthday, or the end of the study period (June 2016). RSV hospitalizations were identified using a validated algorithm based on International Classification of Diseases, 10th Revision, and/or laboratory-confirmed outcomes. We calculated hospitalization rates by various characteristics of interest, including calendar month, age groups, sex, comorbidities, and gestational age., Results: The overall RSV hospitalization rate for children <5 years was 4.2 per 1000 person-years (PY) with a wide range across age groups (from 29.6 to 0.52 per 1000 PY in children aged 1 month and 36-59 months, respectively). Rates were higher in children born at a younger gestational age (23.2 per 1000 PY for those born at <28 weeks versus 3.9 per 1000 PY born at ≥37 weeks); this increased risk persisted as age increased. While the majority of children in our study had no comorbidities, rates were higher in children with comorbidities. For all age groups, rates were highest between December and March., Conclusions: Our results confirm the high burden of RSV hospitalization and highlight young infants are at additional risk, namely premature infants. These results can inform prevention efforts., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Background: Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk., Methods: Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status., Results: Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%-20%] and 17% [13%-21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10-1.21] and 1.15 [1.10-1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for β-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated β-blocker users., Conclusions: Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding., Competing Interests: Potential conflicts of interest. H. C., M. A. C., S. A. B., T. K., K. L. S., and J. C. K. report support from the Canadian Institutes of Health Research (CIHR; grant PJT 159516, paid to the institution). J. B. G. has received research grants from GSK and Hoffmann-LaRoche for antiviral resistance studies and from Pfizer to conduct microbiological surveillance of Streptococcus pneumoniae. J. B. G. also reports consulting fees from GIDEON Informatics, as a scientific editor, unrelated to the current work. A. J. M. reports research funds from GSK; grants or contracts from Sanofi, Merck, and Pfizer (paid to the institution); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Merck, Biogen, and Moderna; and participation on a data safety monitoring board or advisory board for Pfizer, GlaxoSmithKline, Moderna, Medicago, Janssen, AstraZeneca, Novavax, and Sanofi. D. C. R. reports participation on a data safety monitoring board or advisory board for GlaxoSmithKline (advisory board meeting on monoclonal antibodies for coronavirus disease 2019 [COVID-19]). M. S. reports grants or contracts from CIHR, Air Canada (staff and reagent costs for the COVID in International Travelers Study), the Ontario Research Fund (equipment costs for COVID-19 automation), and the Juravinski Research Fund (staff and equipment for COVID-19 diagnostic testing). G. Z. reports support from CIHR (paid to grant administered by J. C. K.) and grants from Genome Atlantic and PHAC. Roche and Abbott contribute unrestricted educational funding to the Eastern Health Regional Health Authority for employees, which include G. Z., to attend virtual meetings and, in specific restricted circumstances, travel to educational, technical, and research meetings. G. Z. is also the previous president of the National Molecular Users Group. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To assess risk of adverse pregnancy, fetal, and neonatal outcomes after a third dose (first booster dose) of covid-19 vaccine during pregnancy among individuals who had completed both doses of primary covid-19 vaccine series before pregnancy., Design: Population based, retrospective cohort study., Setting: Ontario, Canada, from 20 December 2021 to 31 August 2022., Participants: Individuals were included if they were pregnant with an expected date of delivery from 20 December 2021 (start date of third dose eligibility for everyone ≥18 years) to 31 August 2022, who had completed the two doses of primary covid-19 messenger RNA vaccine series before pregnancy, and became eligible for a third dose (≥six months since dose two) before the end of pregnancy., Main Outcome Measures: Pregnancy outcomes included hypertensive disorders of pregnancy, placental abruption, caesarean delivery, chorioamnionitis, and postpartum hemorrhage. Fetal and neonatal outcomes included stillbirth, preterm birth, admission to neonatal intensive care unit for >24 h, newborn 5 min Apgar score <7, and small-for-gestational age infant (<10th percentile). We estimated hazard ratios and 95% confidence intervals for study outcomes, treating dose three as a time varying exposure and adjusting for confounding using inverse probability weighting., Results: Among 32 689 births, 18 491 (56.6%) were born to individuals who received a third covid-19 dose during pregnancy. Compared with eligible individuals who did not receive a third dose during pregnancy, no increased risks were associated with receiving a third covid-19 vaccine dose during pregnancy for placental abruption (adjusted hazard ratio 0.84 (95% confidence interval 0.70 to 1.02)), chorioamnionitis (0.67 (0.49 to 0.90)), postpartum haemorrhage (1.01 (0.89 to 1.16)), caesarean delivery (0.90 (0.87 to 0.94)), stillbirth (0.56 (0.39 to 0.81)), preterm birth (0.91 (0.84 to 0.99)), neonatal intensive care unit admission (0.96 (0.90 to 1.03)), 5 min Apgar score<7 (0.96 (0.82 to 1.14)), or small-for-gestational age infant (0.86 (0.79 to 0.93))., Conclusion: Receipt of a third covid-19 vaccine dose during pregnancy was not associated with an increased risk of adverse pregnancy, fetal, or neonatal outcomes. These findings can help to inform evidence based decision making about the risks and benefits of covid-19 booster doses during pregnancy., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; KW is Chief Scientific Officer and a Director for CANImmunize Inc. He has served as a member of safety advisory boards for Medicago and Moderna., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: With the growing volume and complexity of laboratory repositories, it has become tedious to parse unstructured data into structured and tabulated formats for secondary uses such as decision support, quality assurance, and outcome analysis. However, advances in natural language processing (NLP) approaches have enabled efficient and automated extraction of clinically meaningful medical concepts from unstructured reports., Objective: In this study, we aimed to determine the feasibility of using the NLP model for information extraction as an alternative approach to a time-consuming and operationally resource-intensive handcrafted rule-based tool. Therefore, we sought to develop and evaluate a deep learning-based NLP model to derive knowledge and extract information from text-based laboratory reports sourced from a provincial laboratory repository system., Methods: The NLP model, a hierarchical multilabel classifier, was trained on a corpus of laboratory reports covering testing for 14 different respiratory viruses and viral subtypes. The corpus includes 87,500 unique laboratory reports annotated by 8 subject matter experts (SMEs). The classification task involved assigning the laboratory reports to labels at 2 levels: 24 fine-grained labels in level 1 and 6 coarse-grained labels in level 2. A "label" also refers to the status of a specific virus or strain being tested or detected (eg, influenza A is detected). The model's performance stability and variation were analyzed across all labels in the classification task. Additionally, the model's generalizability was evaluated internally and externally on various test sets., Results: Overall, the NLP model performed well on internal, out-of-time (pre-COVID-19), and external (different laboratories) test sets with microaveraged F 1 -scores >94% across all classes. Higher precision and recall scores with less variability were observed for the internal and pre-COVID-19 test sets. As expected, the model's performance varied across categories and virus types due to the imbalanced nature of the corpus and sample sizes per class. There were intrinsically fewer classes of viruses being detected than those tested; therefore, the model's performance (lowest F 1 -score of 57%) was noticeably lower in the detected cases., Conclusions: We demonstrated that deep learning-based NLP models are promising solutions for information extraction from text-based laboratory reports. These approaches enable scalable, timely, and practical access to high-quality and encoded laboratory data if integrated into laboratory information system repositories., (©Elham Dolatabadi, Branson Chen, Sarah A Buchan, Alex Marchand Austin, Mahmoud Azimaee, Allison McGeer, Samira Mubareka, Jeffrey C Kwong. Originally published in JMIR AI (https://ai.jmir.org), 06.06.2023.)

Background: Increased immune evasion by emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and occurrence of breakthrough infections raise questions about whether coronavirus disease 2019 vaccination status affects SARS-CoV-2 viral load among those infected. This study examined the relationship between cycle threshold (Ct) value, which is inversely associated with viral load, and vaccination status at the onset of the Omicron wave onset in Ontario, Canada., Methods: Using linked provincial databases, we compared median Ct values across vaccination status among polymerase chain reaction-confirmed Omicron variant SARS-CoV-2 cases (sublineages B.1.1.529, BA.1, and BA.1.1) between 6 and 30 December 2021. Cases were presumed to be Omicron based on S-gene target failure. We estimated the relationship between vaccination status and Ct values using multiple linear regression, adjusting for age group, sex, and symptom status., Results: Of the 27 029 presumed Omicron cases in Ontario, the majority were in individuals who had received a complete vaccine series (87.7%), followed by unvaccinated individuals (8.1%), and those who had received a booster dose (4.2%). The median Ct value for post-booster dose individuals (18.3 [interquartile range, 15.4-22.3]) was significantly higher than that for unvaccinated (17.9 [15.2-21.6]; P = .02) and post-vaccine series individuals (17.8 [15.3-21.5]; P = .005). Post-booster dose cases remained associated with a significantly higher median Ct value than cases in unvaccinated individuals ( P ≤ .001), after adjustment for covariates. Compared with values in persons aged 18-29 years, Ct values were significantly lower among most age groups >50 years., Conclusions: While slightly lower Ct values were observed among unvaccinated individuals infected with Omicron compared with post-booster dose cases, further research is required to determine whether a significant difference in secondary transmission exists between these groups., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The COVID-19 vaccination program implementation in Ontario, Canada has spanned multiple years and is ongoing. To meet the challenges of the program, Ontario developed and implemented a new electronic COVID-19 immunization registry, COVaxON, which captures individual-level data on all doses administered in the province enabling comprehensive coverage assessment. However, the need for ongoing COVID-19 vaccine coverage assessments over a multi-year vaccination program posed challenges necessitating methodological changes. This paper describes Ontario's COVID-19 immunization registry, the methods implemented over time to allow for the ongoing assessment of vaccine coverage by age, and the impact of those methodological changes. Throughout the course of the vaccination program, four different methodological approaches were used to calculate age-specific coverage estimates using vaccination data (numerator) obtained from COVaxON. Age-specific numerators were initially calculated using age at time of first dose (method A), but were updated to the age at coverage assessment (method B). Database enhancements allowed for the exclusion of deceased individuals from the numerator (method C). Population data (denominator) was updated to 2022 projections from the 2021 national census following their availability (method D). The impact was most evident in older age groups where vaccine uptake was high. For example, coverage estimates for individuals aged 70-79 years of age for at least one dose decreased from 104.9 % (method B) to 95.0 % (method D). Thus, methodological changes improved estimates such that none exceeded 100 %. Ontario's COVID-19 immunization registry has been transformational for vaccine program surveillance. The implementation of a single registry for COVID-19 vaccines was essential for comprehensive near real-time coverage assessment, and enabled new uses of the data to support additional components of vaccine program surveillance. The province is well positioned to build on what has been achieved as a result of the COVID-19 pandemic and expand the registry to other routine vaccination programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

We estimated the effectiveness of a fourth dose of messenger RNA coronavirus disease 2019 vaccine against Omicron infections and severe outcomes over time among long-term care residents in Ontario, Canada. Fourth doses provide additional protection against Omicron-related outcomes, but the protection wanes over time, with more waning seen against infection than severe outcomes., Competing Interests: Potential conflicts of interest. S. E. W. is a member of the National Advisory Committee on Immunization. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: An understanding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission in schools is important. It is often difficult, using epidemiological information alone, to determine whether cases associated with schools represent multiple introductions from the community or transmission within the school. We describe the use of whole genome sequencing (WGS) in multiple schools to investigate outbreaks of SARS-CoV-2 in the pre-Omicron period., Study Design: School outbreaks were identified for sequencing by local public health units based on multiple cases without known epidemiological links. Cases of SARS-CoV-2 from students and staff from 4 school outbreaks in Ontario underwent WGS and phylogenetic analysis. The epidemiological clinical cohort data and genomic cluster data are described to help further characterize these outbreaks., Results: A total of 132 positive SARS-CoV-2 cases among students and staff from 4 school outbreaks were identified with 65 (49%) of cases able to be sequenced with high-quality genomic data. The 4 school outbreaks consisted of 53, 37, 21 and 21 positive cases; within each outbreak there were between 8 and 28 different clinical cohorts identified. Among the sequenced cases, between 3 and 7 genetic clusters, defined as different strains, were identified in each outbreak. We found genetically different viruses within several clinical cohorts., Conclusions: WGS, together with public health investigation, is a useful tool to investigate SARS-CoV-2 transmission within schools. Its early use has the potential to better understand when transmission may have occurred, can aid in evaluating how well mitigation interventions are working and has the potential to reduce unnecessary school closures when multiple genetic clusters are identified., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: The risk of myocarditis or pericarditis after COVID-19 messenger RNA vaccines varies by age and sex, and there is some evidence to suggest increasing risk with shorter intervals between dose 1 and 2 (ie, interdose interval)., Objective: To estimate the incidence of reported myocarditis or pericarditis after BNT162b2 vaccine among adolescents and to describe the clinical information associated with these events., Design, Setting, and Participants: This was a population-based cohort study using passive vaccine safety surveillance data linked to the provincial COVID-19 vaccine registry. Included in the study were all adolescents aged 12 to 17 years in Ontario, Canada, who received 1 or more doses of BNT162b2 vaccine between December 14, 2020, and November 21, 2021, and reported an episode of myocarditis or pericarditis. Data were analyzed from December 15, 2021, to April 22, 2022., Exposure: Receipt of BNT162b2 (Comirnaty [Pfizer-BioNTech]) vaccine., Main Outcomes and Measure: Reported incidence of myocarditis or pericarditis meeting level 1 to 3 of the Brighton Collaboration case definition per 100 000 doses of BNT162b2 administered by age group (12-15 years vs 16-17 years), sex, dose number, and interdose interval. All clinical information associated with symptoms, health care usage, diagnostic test results, and treatment at the time of the acute event were summarized., Results: There were approximately 1.65 million doses of BNT162b2 administered and 77 reports of myocarditis or pericarditis among those aged 12 to 17 years, which met the inclusion criteria during the study period. Of the 77 adolescents (mean [SD] age, 15.0 [1.7] years; 63 male individuals [81.8%]), 51 (66.2%) developed myocarditis or pericarditis after dose 2 of BNT162b2. Overall, 74 individuals (96.1%) with an event were assessed in the emergency department, and 34 (44.2%) were hospitalized (median [IQR] length of stay, 1 [1-2] day). The majority of adolescents (57 [74.0%]) were treated with nonsteroidal anti-inflammatory drugs only, and 11 (14.3%) required no treatment. The highest reported incidence was observed among male adolescents aged 16 to 17 years after dose 2 (15.7 per 100 000; 95% CI, 9.7-23.9). Among those aged 16 to 17 years, the reporting rate was highest in those with a short (ie, ≤30 days) interdose interval (21.3 per 100 000; 95% CI, 11.0-37.2)., Conclusions and Relevance: Results of this cohort study suggest that there was variation in the reported incidence of myocarditis or pericarditis after BNT162b2 vaccine among adolescent age groups. However, the risk of these events after vaccination remains very rare and should be considered in relation to the benefits of COVID-19 vaccination.

Competing Interests: We declare no competing interests.

Objectives: This study aimed to provide real-world evidence on coronavirus disease 2019 vaccine effectiveness (VE) against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years., Methods: We used the test-negative study design and linked provincial databases to estimate BNT162b2 vaccine effectiveness against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years between January 2 and August 27, 2022 in Ontario. We used multivariable logistic regression to estimate VE by time since the latest dose, compared with unvaccinated children, and we evaluated VE by dosing interval., Results: We included 6284 test-positive cases and 8389 test-negative controls. VE against symptomatic infection declined from 24% (95% confidence interval [CI], 8% to 36%) 14 to 29 days after a first dose and 66% (95% CI, 60% to 71%) 7 to 29 days after 2 doses. VE was higher for children with dosing intervals of ≥56 days (57% [95% CI, 51% to 62%]) than 15 to 27 days (12% [95% CI, -11% to 30%]) and 28 to 41 days (38% [95% CI, 28% to 47%]), but appeared to wane over time for all dosing interval groups. VE against severe outcomes was 94% (95% CI, 57% to 99%) 7 to 29 days after 2 doses and declined to 57% (95%CI, -20% to 85%) after ≥120 days., Conclusions: In children aged 5 to 11 years, 2 doses of BNT162b2 provide moderate protection against symptomatic Omicron infection within 4 months of vaccination and good protection against severe outcomes. Protection wanes more rapidly for infection than severe outcomes. Overall, longer dosing intervals confer higher protection against symptomatic infection, however protection decreases and becomes similar to shorter dosing interval starting 90 days after vaccination.

Background: Vaccines against SARS-CoV-2 have been shown to reduce risk of infection as well as severe disease among those with breakthrough infection in adults. The latter effect is particularly important as immune evasion by Omicron variants appears to have made vaccines less effective at preventing infection. Therefore, we aimed to quantify the protection conferred by mRNA vaccination against hospitalization due to SARS-CoV-2 in adolescent and pediatric populations., Methods: We retrospectively created a cohort of reported SARS-CoV-2 case records from Ontario's Public Health Case and Contact Management Solution among those aged 4 to 17 linked to vaccination records from the COVaxON database on January 19, 2022. We used multivariable logistic regression to estimate the association between vaccination and hospitalization among SARS-CoV-2 cases prior to and during the emergence of Omicron., Results: We included 62 hospitalized and 27,674 non-hospitalized SARS-CoV-2 cases, with disease onset from May 28, 2021 to December 4, 2021 (Pre-Omicron) and from December 23, 2021 to January 9, 2022 (Omicron). Among adolescents, two mRNA vaccine doses were associated with an 85% (aOR = 0.15; 95% CI: [0.04, 0.53]; p<0.01) lower likelihood of hospitalization among SARS-CoV-2 cases caused by Omicron. Among children, one mRNA vaccine dose was associated with a 79% (aOR = 0.21; 95% CI: [0.03, 0.77]; p<0.05) lower likelihood of hospitalization among SARS-CoV-2 cases caused by Omicron. The calculation of E-values, which quantifies how strong an unmeasured confounder would need to be to nullify our findings, suggest that these effects are unlikely to be explained by unmeasured confounding., Conclusions: Despite immune evasion by SARS-CoV-2 variants, vaccination continues to be associated with a lower likelihood of hospitalization among adolescent and pediatric Omicron (B.1.1.529) SARS-CoV-2 cases, even when the vaccines do not prevent infection. Continued efforts are needed to increase vaccine uptake among adolescent and pediatric populations., Competing Interests: DNF has served on advisory boards related to influenza and SARS-CoV-2 vaccines for Seqirus, Pfizer, AstraZeneca, and Sanofi-Pasteur Vaccines, and has served as a legal expert on issues related to COVID-19 epidemiology for the Elementary Teachers Federation of Ontario and the Registered Nurses Association of Ontario. ART was employed by the Public Health Agency of Canada when the research was conducted. The work does not represent the views of the Public Health Agency of Canada. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Simmons et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We estimated the effectiveness of booster doses of monovalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults in Ontario, Canada. We used a test-negative design to estimate vaccine effectiveness (VE) against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years from January 2 to October 1, 2022, stratified by age and time since vaccination. We also compared VE during BA.1/BA.2 and BA.4/BA.5 sublineage predominance. We included 11,160 cases and 62,880 tests for test-negative controls. Depending on the age group, compared to unvaccinated adults, VE was 91-98% 7-59 days after a third dose, waned to 76-87% after ≥240 days, was restored to 92-97% 7-59 days after a fourth dose, and waned to 86-89% after ≥120 days. VE was lower and declined faster during BA.4/BA.5 versus BA.1/BA.2 predominance, particularly after ≥120 days. Here we show that booster doses of monovalent mRNA COVID-19 vaccines restored strong protection against severe outcomes for at least 3 months after vaccination. Across the entire study period, protection declined slightly over time, but waned more during BA.4/BA.5 predominance., (© 2023. Crown.)

Background: Population-based COVID-19 vaccine coverage estimates among pregnant individuals are limited. We assessed temporal patterns in vaccine coverage (≥1 dose before or during pregnancy) and evaluated factors associated with vaccine series initiation (receiving dose 1 during pregnancy) in Ontario, Canada., Methods: We linked the provincial birth registry with COVID-19 vaccination records from December 14, 2020 to December 31, 2021 and assessed coverage rates among all pregnant individuals by month, age, and neighborhood sociodemographic characteristics. Among individuals who gave birth since April 2021-when pregnant people were prioritized for vaccination-we assessed associations between sociodemographic, behavioral, and pregnancy-related factors with vaccine series initiation using multivariable regression to estimate adjusted risk ratios (aRR) and risk differences (aRD) with 95% confidence intervals (CI)., Results: Among 221,190 pregnant individuals, vaccine coverage increased to 71.2% by December 2021. Gaps in coverage across categories of age and sociodemographic characteristics decreased over time, but did not disappear. Lower vaccine series initiation was associated with lower age (<25 vs. 30-34 years: aRR 0.53, 95%CI 0.51-0.56), smoking (vs. non-smoking: 0.64, 0.61-0.67), no first trimester prenatal care visit (vs. visit: 0.80, 0.77-0.84), and residing in neighborhoods with the lowest income (vs. highest: 0.69, 0.67-0.71). Vaccine series initiation was marginally higher among individuals with pre-existing medical conditions (vs. no conditions: 1.07, 1.04-1.10)., Conclusions: COVID-19 vaccine coverage among pregnant individuals remained lower than in the general population, and there was lower vaccine initiation by multiple characteristics., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K. Wilson is CEO of CANImmunize Inc, which hosts a national digital immunization record, and is a member of the independent data safety board for the Medicago COVID-19 vaccine trial; there were no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A major goal of coronavirus disease 2019 (COVID-19) vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of messenger RNA (mRNA) and ChAdOx1 COVID-19 vaccines against severe outcomes in 4 Canadian provinces between December 2020 and September 2021., Methods: We conducted this multiprovincial, retrospective, test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random-effects models., Results: We included 2 508 296 tested participants, with 31 776 COVID-19 hospitalizations and 5842 deaths. Vaccine effectiveness was 83% after a first dose and 98% after a second dose against both hospitalization and death (separately). Against severe outcomes, effectiveness was 87% (95% confidence interval [CI], 71%-94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95% CI, 96%-99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95% CI, 75%-94%) ≥56 days after a first dose, increasing to 97% (95% CI, 91%-99%) ≥56 days after a second dose. Lower 1-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules and against Alpha, Gamma, and Delta variants., Conclusions: Two doses of mRNA or ChAdOx1 vaccine provide excellent protection against severe outcomes., Competing Interests: Potential conflicts of interest. C. H. R. has received an unrestricted research grant from Pfizer for an unrelated study. S. M. M. received unrestricted research grants from GlaxoSmithKline (GSK), Merck, Pfizer, Roche-Assurex, and Sanofi Pasteur for unrelated studies and is/was a member of advisory boards for GSK, Merck, Sanofi Pasteur, and Seqirus and reports consulting fees from these companies. M. K. received contracts to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–infected blood donors from Abcellera and to evaluate SARS-CoV-2 serology tests from Siemens; both unrelated to this study. G. D. S. received a grant from Pfizer for a meningococcal antibody seroprevalence study not related to this study with payments to his institution. M. T. reports grants or contracts from the Canadian Institutes of Health Research and the Ontario Ministry of Health unrelated to this work and consulting fees from the Canadian Agency for Drugs and Technologies in Health and Green Shield Canada. N. Z. J. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie and participation on a data and safety monitoring board or advisory board for AbbVie. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© Queen's Printer for Ontario, 2022.)

Objective: To estimate the effectiveness of maternal mRNA covid-19 vaccination during pregnancy against delta and omicron severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and hospital admission in infants., Design: Test negative design study., Setting: Community and hospital testing in Ontario, Canada., Participants: Infants younger than six months of age, born between 7 May 2021 and 31 March 2022, who were tested for SARS-CoV-2 between 7 May 2021 and 5 September 2022., Intervention: Maternal mRNA covid-19 vaccination during pregnancy., Main Outcome Measures: Laboratory confirmed delta or omicron infection or hospital admission of the infant. Multivariable logistic regression estimated vaccine effectiveness, with adjustments for clinical and sociodemographic characteristics associated with vaccination and infection., Results: 8809 infants met eligibility criteria, including 99 delta cases (4365 controls) and 1501 omicron cases (4847 controls). Infant vaccine effectiveness from two maternal doses was 95% (95% confidence interval 88% to 98%) against delta infection and 97% (73% to 100%) against infant hospital admission due to delta and 45% (37% to 53%) against omicron infection and 53% (39% to 64%) against hospital admission due to omicron. Vaccine effectiveness for three doses was 73% (61% to 80%) against omicron infection and 80% (64% to 89%) against hospital admission due to omicron. Vaccine effectiveness for two doses against infant omicron infection was highest with the second dose in the third trimester (53% (42% to 62%)) compared with the first (47% (31% to 59%)) or second (37% (24% to 47%)) trimesters. Vaccine effectiveness for two doses against infant omicron infection decreased from 57% (44% to 66%) between birth and eight weeks to 40% (21% to 54%) after 16 weeks of age., Conclusions: Maternal covid-19 vaccination with a second dose during pregnancy was highly effective against delta and moderately effective against omicron infection and hospital admission in infants during the first six months of life. A third vaccine dose bolstered protection against omicron. Effectiveness for two doses was highest with maternal vaccination in the third trimester, and effectiveness decreased in infants beyond eight weeks of age., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Public Health Agency of Canada, the Canadian Institutes of Health Research, and the Ontario Ministry of Health and the Ministry of Long term Care for the submitted work; KW is chief executive officer of CANImmunize and serves on the data safety board for the Medicago covid-19 vaccine trial., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pregnant women are recommended to receive coronavirus disease 2019 (COVID-19) vaccines; however, relative effectiveness of vaccination by pregnancy status is unclear., Methods: We compared the relative effectiveness of messenger RNA (mRNA) COVID-19 vaccines according to whether women received both doses while pregnant (n = 7412), 1 dose while pregnant (n = 3538), both doses while postpartum (n = 1856), or both doses while neither pregnant nor postpartum (n = 6687). We estimated risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection starting 14 days after the second dose using Cox regression, reporting hazard ratios (HRs) and 95% confidence intervals (CIs). Second, we examined relative effectiveness of a third (booster) dose while pregnant compared to outside pregnancy. The major circulating variant during the study period was the Delta variant., Results: Fifty-four percent of women received 2 doses of the BNT162b2 vaccine, 16% received 2 doses of the mRNA-1273 vaccine, while 30% received 1 dose of both vaccines. Compared to women who received both doses while neither pregnant nor postpartum, the adjusted HR for a positive SARS-CoV-2 polymerase chain reaction test was similar if the woman received both doses while pregnant (1.04 [95% CI, .94-1.17]), 1 dose while pregnant and 1 dose before or after pregnancy (1.03 [95% CI, .93-1.14]), or both doses while postpartum (0.99 [95% CI, .92-1.07]). The findings were similar for BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax), and during Delta- and Omicron-dominant periods. We observed no differences in the relative effectiveness of the booster dose according to pregnancy status., Conclusions: We observed similar effectiveness of mRNA vaccines against SARS-CoV-2 infection among women regardless of pregnancy status at the time of vaccination., Competing Interests: Potential conflicts of interest. S. B., D. B. F., and J. C. K. report co-investigator grants for COVID-19 vaccine monitoring in pregnancy in Ontario, Canada, from the COVID-19 Immunity Task Force, Public Health Agency of Canada. E. O. C. reports grants or contracts from the Norwegian Research Council. D. B. F. reports travel support to present on COVID-19 vaccine safety during pregnancy at the World Vaccine Congress, Washington, D.C., April 2022, and a Liaison Member of Canada's National Advisory Committee on Immunization. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: People with HIV were underrepresented in coronavirus disease 2019 (COVID-19) vaccine clinical trials. We estimated vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for the BNT162b2, mRNA-1273, and ChAdOx1 vaccines among a population-based cohort of people with HIV in Ontario, Canada., Design: Test-negative design., Methods: We identified people with HIV aged ≥19 years who were tested for SARS-CoV-2 by RT-PCR between December 14, 2020 (first availability of COVID-19 vaccines) and November 21, 2021 (pre-Omicron circulation). Outcomes included any infection, symptomatic infection, and COVID-19-related hospitalization/death. We compared the odds of vaccination between test-positive cases and test-negative controls using multivariable logistic regression with adjustment for age, sex, region, calendar time, SARS-CoV-2 test histories, influenza vaccination, comorbidities, and neighborhood-level socio-economic status. VE was derived as (1 - adjusted odds ratio) × 100%., Results: Among 21 023 adults living with HIV, there were 801 (8.3%) test-positive cases and 8,879 (91.7%) test-negative controls. 20.1% cases and 47.8% of controls received ≥1 COVID-19 vaccine dose; among two-dose recipients, 93.4% received ≥1 mRNA dose. Two-dose VE ≥7 days before specimen collection was 82% (95% confidence interval [CI] = 74-87%) against any infection, 94% (95% CI = 82-98%) against symptomatic infection, and 97% (95% CI = 85-100%) against hospitalization/death. Against any infection, VE declined from 86% (95% CI = 77-92%) within 7-59 days after the second dose to 66% (95% CI = -15-90%) after ≥180 days; we did not observe evidence of waning protection for other outcomes., Conclusion: Two doses of COVID-19 vaccine offered substantial protection against symptomatic illness and hospitalization/death in people with HIV prior to the emergence of the Omicron variant. Our findings do not support a broad conclusion that COVID-19 VE is lower among people with HIV in populations that, for the most part, are attending HIV care, taking antiretroviral medication, and are virally suppressed., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: We aimed to estimate associations between COVID-19 incidence and mortality with neighbourhood-level immigration, race, housing, and socio-economic characteristics., Methods: We conducted a population-based study of 28,808 COVID-19 cases in the provincial reportable infectious disease surveillance systems (Public Health Case and Contact Management System) which includes all known COVID-19 infections and deaths from Ontario, Canada reported between January 23, 2020 and July 28, 2020. Residents of congregate settings, Indigenous communities living on reserves or small neighbourhoods with populations <1,000 were excluded. Comparing neighbourhoods in the 90th to the 10th percentiles of socio-demographic characteristics, we estimated the associations between 18 neighbourhood-level measures of immigration, race, housing and socio-economic characteristics and COVID-19 incidence and mortality using Poisson generalized linear mixed models., Results: Neighbourhoods with the highest proportion of immigrants (relative risk (RR): 4.0, 95%CI:3.5-4.5) and visible minority residents (RR: 3.3, 95%CI:2.9-3.7) showed the strongest association with COVID-19 incidence in adjusted models. Among individual race groups, COVID-19 incidence was highest among neighbourhoods with the high proportions of Black (RR: 2.4, 95%CI:2.2-2.6), South Asian (RR: 1.9, 95%CI:1.8-2.1), Latin American (RR: 1.8, 95%CI:1.6-2.0) and Middle Eastern (RR: 1.2, 95%CI:1.1-1.3) residents. Neighbourhoods with the highest average household size (RR: 1.9, 95%CI:1.7-2.1), proportion of multigenerational families (RR: 1.8, 95%CI:1.7-2.0) and unsuitably crowded housing (RR: 2.1, 95%CI:2.0-2.3) were associated with COVID-19 incidence. Neighbourhoods with the highest proportion of residents with less than high school education (RR: 1.6, 95%CI:1.4-1.8), low income (RR: 1.4, 95%CI:1.2-1.5) and unaffordable housing (RR: 1.6, 95%CI:1.4-1.8) were associated with COVID-19 incidence. Similar inequities were observed across neighbourhood-level sociodemographic characteristics and COVID-19 mortality., Conclusions: Neighbourhood-level inequities in COVID-19 incidence and mortality were observed in Ontario, with excess burden experienced in neighbourhoods with a higher proportion of immigrants, racialized populations, large households and low socio-economic status., Competing Interests: The authors have declared that no competing interests exist.

Background: Influenza vaccination is recommended in Canada for older adults and those with underlying health conditions due to their increased risk of severe outcomes. Further research is needed to identify who within these groups is not receiving influenza vaccine to identify opportunities to increase coverage., Objectives: We aimed to 1) estimate influenza non-vaccination prevalence and 2) assess factors associated with non-vaccination among Canadian adults aged ≥65 and adults aged 46-64 with ≥1 chronic medical condition (CMC) due to their high risk of severe influenza outcomes., Methods: We conducted a secondary analysis of cross-sectional data collected from 2015-2018 among participants of the Canadian Longitudinal Study on Aging. For both groups of interest, we estimated non-vaccination prevalence and used logistic regression models to identify factors associated with non-vaccination. We report adjusted odds ratios and 95% confidence intervals for the investigated variables., Results: Overall, 29.5% (95% CI: 28.9%, 30.1%) of the 23,226 participants aged ≥65 years and 50.4% (95% CI: 49.4%, 51.3%) of the 11,250 participants aged 46-64 years with ≥1 CMC reported not receiving an influenza vaccination in the past 12 months. For both groups, lack of recent contact with a family doctor and current smoking were independently associated with non-vaccination., Discussion: Influenza vaccination helps prevent severe influenza outcomes. Yet, half of adults aged 46-64 years with ≥1 CMC and more than one-quarter of all adults aged ≥65 years did not receive a recommended influenza vaccine in the year prior to the survey. Innovation in vaccination campaigns for routinely recommended vaccines, especially among those without annual family doctor visits, may improve coverage., Conclusion: Influenza vaccination coverage among Canadian adults aged 46-64 years with ≥1 CMC and adults aged ≥65 years remains suboptimal. Vaccination campaigns targeting those at high risk of severe outcomes without routine physician engagement should be evaluated to improve uptake., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MKA reports grant funding from Sanofi, GSK, Pfizer, the Public Health Agency of Canada and the Canadian Frailty Network, and payments for past advisory activities from Sanofi, Pfizer and Sequirus. All other authors report no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Competing Interests: Competing interests: Beate Sander reports receiving funding from the Ministry of Colleges and Universities as Principal Investigator of a COVID-19 Rapid Research Fund. Until March 2022, Dr. Sander served as co-chair of the Ontario COVID-19 Modelling Consensus Table. Sarah Buchan reports being the co-investigator on grants to support COVID-19 epidemiology and immunization-related research funded by the Canadian Institutes of Health Research (CIHR) and the Public Health Agency of Canada (PHAC). Jeffrey Kwong reports receiving grants to support COVID-19 epidemiology and immunization-related research funded by CIHR and PHAC. Dr. Kwong has also received a University of Toronto Department of Family and Community Medicine Clinician-Scientist Award. Sharmistha Mishra reports receiving grants to support COVID-19 epidemiology and modelling research funded by CIHR. Dr. Mishra is also a member of the Ontario COVID-19 Modelling Consensus Table and is funded by a Tier 2 Canada Research Chair in Mathematical Modelling and Program Science. Laura Rosella is funded by a Canada Research Chair in Population Health Analytics and the Stephen Family Chair in Community Health, Trillium Health Partners Foundation. No other competing interests were declared.

Background: Waning protection from 2 doses of coronavirus disease 2019 (COVID-19) vaccines led to third dose availability in multiple countries even before the emergence of the Omicron variant., Methods: We used the test-negative study design to estimate vaccine effectiveness (VE) against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, any symptomatic infection, and severe outcomes (COVID-19-related hospitalizations or death) by time since second dose of any combination of BNT162b2, mRNA-1273, and ChAdOx1 between January 11, and November 21, 2021, for subgroups based on patient and vaccine characteristics., Results: We included 261 360 test-positive cases (of any SARS-CoV-2 lineage) and 2 783 699 individuals as test-negative controls. VE of 2 mRNA vaccine doses decreased from 90% (95% CI, 90%-90%) 7-59 days after the second dose to 75% (95% CI, 72%-78%) after ≥240 days against infection, decreased from 94% (95% CI, 84%-95%) to 87% (95% CI, 85%-89%) against symptomatic infection, and remained stable (98% [95% CI, 97%-98%] to 98% [95% CI, 96%-99%]) against severe outcomes. Similar trends were seen with heterologous ChAdOx1 and mRNA vaccine schedules. VE estimates for dosing intervals <35 days were lower than for longer intervals (eg, VE of 2 mRNA vaccines against symptomatic infection at 120-179 days was 86% [95% CI, 85%-88%] for dosing intervals <35 days, 92% [95% CI, 91%-93%] for 35-55 days, and 91% [95% CI, 90%-92%] for ≥56 days), but when stratified by age group and subperiod, there were no differences between dosing intervals., Conclusions: Before the emergence of Omicron, VE of any 2-dose primary series, including heterologous schedules and varying dosing intervals, decreased over time against any infection and symptomatic infection but remained high against severe outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: The incidence of SARS-CoV-2 infection, including among individuals who have received 2 doses of COVID-19 vaccine, increased substantially following the emergence of the Omicron variant in Ontario, Canada. Understanding the estimated effectiveness of 2 or 3 doses of COVID-19 vaccine against outcomes associated with Omicron and Delta infections may aid decision-making at the individual and population levels., Objective: To estimate vaccine effectiveness (VE) against symptomatic infections due to the Omicron and Delta variants and severe outcomes (hospitalization or death) associated with these infections., Design, Setting, and Participants: This test-negative case-control study used linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination, and health administration in Ontario, Canada. Participants were individuals aged 18 years or older who had COVID-19 symptoms or severe outcomes (hospitalization or death) and were tested for SARS-CoV-2 between December 6 and 26, 2021., Exposures: Receipt of 2 or 3 doses of the COVID-19 vaccine and time since last dose., Main Outcomes and Measures: The main outcomes were symptomatic Omicron or Delta infection and severe outcomes (hospitalization or death) associated with infection. Multivariable logistic regression was used to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose compared with no vaccination. Estimated VE was calculated using the formula VE = (1 - [adjusted odds ratio]) × 100%., Results: Of 134 435 total participants, 16 087 were Omicron-positive cases (mean [SD] age, 36.0 [14.1] years; 8249 [51.3%] female), 4261 were Delta-positive cases (mean [SD] age, 44.2 [16.8] years; 2199 [51.6%] female), and 114 087 were test-negative controls (mean [SD] age, 42.0 [16.5] years; 67 884 [59.5%] female). Estimated VE against symptomatic Delta infection decreased from 89% (95% CI, 86%-92%) 7 to 59 days after a second dose to 80% (95% CI, 74%-84%) after 240 or more days but increased to 97% (95% CI, 96%-98%) 7 or more days after a third dose. Estimated VE against symptomatic Omicron infection was 36% (95% CI, 24%-45%) 7 to 59 days after a second dose and 1% (95% CI, -8% to 10%) after 180 days or longer, but 7 or more days after a third dose, it increased to 61% (95% CI, 56%-65%). Estimated VE against severe outcomes was high 7 or more days after a third dose for both Delta (99%; 95% CI, 98%-99%) and Omicron (95%; 95% CI, 87%-98%)., Conclusions and Relevance: In this study, in contrast to high estimated VE against symptomatic Delta infection and severe outcomes after 2 doses of COVID-19 vaccine, estimated VE was modest and short term against symptomatic Omicron infection but better maintained against severe outcomes. A third dose was associated with improved estimated VE against symptomatic infection and with high estimated VE against severe outcomes for both variants. Preventing infection due to Omicron and potential future variants may require tools beyond the currently available vaccines.

Objective: To assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy., Design: Population based retrospective cohort study., Setting: Ontario, Canada, 1 May to 31 December 2021., Participants: All liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g., Main Outcome Measures: Using Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (<32 weeks), small for gestational age at birth (<10th centile), and stillbirth. Vaccination against covid-19 was treated as a time varying exposure in the outcome specific risk window, and propensity score weighting was used to adjust hazard ratios for potential confounding., Results: Among 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy-42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinated v 6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7% v 4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59% v 0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1% v 9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25% v 0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy., Conclusion: The findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Public Health Agency of Canada through the Vaccine Surveillance Reference Group and the COVID-19 Immunity Task Force; SEH and LO were partly funded by the Norwegian Research Council. KW is chief executive officer of CANImmunize, which hosts a national digital immunisation record, and is a member of the independent data safety board for the Medicago covid-19 vaccine trial. There are no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA covid-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the omicron variant., Design: Test negative design., Setting: Long term care facilities in Ontario, Canada, 30 December 2021 to 27 April 2022., Participants: After exclusions, 61 344 residents aged 60 years or older across 626 long term care facilities in Ontario, Canada who were tested for SARS-CoV-2 were included., Main Outcome Measures: Laboratory confirmed omicron SARS-CoV-2 infection (any and symptomatic) by reverse transcription polymerase chain reaction (RT-PCR), and hospital admission or death. Multivariable logistic regression was used to estimate marginal effectiveness (four versus three doses) and vaccine effectiveness (two, three, or four doses versus no doses) while adjusting for personal characteristics, comorbidities, week of test, and previous positive SARS-CoV-2 test result more than 90 days previously., Results: 13 654 residents who tested positive for omicron SARS-CoV-2 infection and 205 862 test negative controls were included. The marginal effectiveness of a fourth dose (95% of vaccine recipients received mRNA-1273 as the fourth dose) seven days or more after vaccination versus a third dose received 84 or more days previously was 19% (95% confidence interval 12% to 26%) against infection, 31% (20% to 41%) against symptomatic infection, and 40% (24% to 52%) against severe outcomes. Vaccine effectiveness in vaccine recipients (compared with unvaccinated) increased with each additional dose, and for a fourth dose was 49% (95% confidence interval 43% to 54%) against infection, 69% (61% to 76%) against symptomatic infection, and 86% (81% to 90%) against severe outcomes., Conclusions: The findings suggest that compared with a third dose of mRNA covid-19 vaccine, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes among long term care residents during an omicron dominant period. A fourth vaccine dose was associated with strong protection against severe outcomes in vaccinated residents compared with unvaccinated residents, although the duration of protection remains unknown., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Applied Health Research Questions Portfolio at ICES, which is funded by the Ontario Ministry of Health, for the submitted work, and no financial relationships with any organisations that might have an interest in the submitted work in the previous three years. SEW is a member of Canada’s National Advisory Committee on Immunization (NACI) and APC is a member of the Congregate Care Setting Working Group of the Ontario Science Table., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The objective of our study was to estimate the rate of workplace outbreak-associated cases of COVID-19 by industry in labour market participants aged 15-69 years who reported working the majority of hours outside the home in Ontario, Canada., Methods: We conducted a population-based cross-sectional study of COVID-19 workplace outbreaks and associated cases reported in Ontario between 1 April 2020 and 31 March 2021. All outbreaks were manually classified into two-digit North American Industry Classification System codes. We obtained monthly denominator estimates from the Statistics Canada Labour Force Survey to estimate the incidence of outbreak-associated cases per 100 000 000 hours among individuals who reported the majority of hours were worked outside the home. We performed this analysis across industries and in three distinct time periods., Results: Overall, 12% of cases were attributed to workplace outbreaks among working-age adults across our study period. While incidence varied across the time periods, the five industries with the highest incidence rates across our study period were agriculture, healthcare and social assistance, food manufacturing, educational services, and transportation and warehousing., Conclusions: Certain industries have consistently increased the incidence of COVID-19 over the course of the pandemic. These results may assist in ongoing efforts to reduce transmission of COVID-19 by prioritising resources, as well as industry-specific guidance, vaccination and public health messaging., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Respiratory syncytial virus (RSV) is a major cause of acute respiratory infection (ARI), with high morbidity and mortality worldwide. RSV costing and burden estimates can highlight the potential benefits of future vaccination programs and are essential for economic evaluations., Objective: We aimed to determine RSV healthcare costs across age groups and the overall disease burden of medically attended RSV in Canada., Methods: We conducted a retrospective case-control study to estimate the attributable healthcare costs per RSV case in Alberta. We used two case definitions to capture diversity in case severity: laboratory-confirmed RSV and ARI attributable to RSV. Matching occurred on five criteria: (1) age, (2) urban/rural status, (3) sex, (4) prematurity and (5) Charlson Comorbidity Index score. We calculated the age-specific burden of medically attended RSV in Canada from 2010 to 2019 by multiplying the weekly age-specific incidence of medically attended ARI with the RSV positivity rate., Results: Costs per laboratory-confirmed RSV case were (in Canadian dollars [CAD], year 2020 values) $CAD12,713 and 40,028 in the first 30 and 365 days following diagnosis, respectively, whereas a case of ARI potentially attributable to RSV cost $CAD316 and 915, in 30 and 365 days, respectively. Older (aged ≥ 65 years) and younger (aged < 90 days) age groups had the highest case costs. The average medically attended RSV incidence rate across nine seasons was 1743 cases per 100,000 people per year., Conclusions: RSV is a common and expensive infection at the extremes of life, and the development of immunization programs targeting older and younger ages may be important for the reduction of RSV burden and cost., (© 2022. The Author(s).)

Importance: Increased rates of myocarditis or pericarditis following receipt of COVID-19 mRNA vaccines have been observed. However, few available data are associated with differences in rates of myocarditis or pericarditis specific to vaccine products, which may have important implications for vaccination programs., Objective: To estimate rates of reported myocarditis or pericarditis following receipt of a COVID-19 mRNA vaccine by product, age, sex, dose number, and interdose interval., Design, Setting, and Participants: This population-based cohort study was conducted in Ontario, Canada (population: 14.7 million) from December 2020 to September 2021 and used data from Ontario's COVID-19 vaccine registry and passive vaccine-safety surveillance system. All individuals in Ontario, Canada, who received at least 1 dose of COVID-19 mRNA vaccine between December 14, 2020, and September 4, 2021, and had a reported episode of myocarditis or pericarditis following receipt of the COVID-19 vaccine during this period were included. We obtained information on all vaccine doses administered in the province to calculate reported rates of myocarditis or pericarditis., Exposures: Receipt of a COVID-19 mRNA vaccine (mRNA-1273 [Moderna Spikevax] or BNT162b2 [Pfizer-BioNTech Comirnaty])., Main Outcomes and Measures: All reports of myocarditis or pericarditis meeting levels 1 to 3 of the Brighton Collaboration case definitions were included. Rates and 95% CIs of reported cases of myocarditis or pericarditis per 1 000 000 mRNA vaccine doses administered were calculated by age, sex, dose number, vaccine product, and interdose interval., Results: Among 19 740 741 doses of mRNA vaccines administered, there were 297 reports of myocarditis or pericarditis meeting the inclusion criteria; 228 (76.8%) occurred in male individuals, and the median age of individuals with a reported event was 24 years (range, 12-81 years). Of the reported cases, 207 (69.7%) occurred following the second dose of the COVID-19 mRNA vaccine. When restricted to individuals who received their second dose during the period of enhanced passive surveillance (on or after June 1, 2021), the highest rate of myocarditis or pericarditis was observed in male individuals aged 18 to 24 years following mRNA-1273 as the second dose (299.5 cases per 1 000 000 doses; 95% CI, 171.2-486.4 cases per 1 000 000 doses); the rate following BNT162b2 as the second dose was 59.2 cases per 1 000 000 doses (95% CI, 19.2-138.1 cases per 1 000 000 doses). Overall rates for both vaccine products were significantly higher when the interdose interval was 30 or fewer days (BNT162b2: 52.1 cases per 1 000 000 doses [95% CI, 31.8-80.5 cases per 1 000 000 doses]; mRNA-1273: 83.9 cases per 1 000 000 doses [95% CI, 47.0-138.4 cases per 1 000 000 doses]) compared with 56 or more days (BNT162b2: 9.6 cases per 1 000 000 doses [95% CI, 6.5-13.6 cases per 1 000 000 doses]; mRNA-1273: 16.2 cases per 1 000 000 doses [95% CI, 10.2-24.6 cases per 1 000 000 doses])., Conclusions and Relevance: The findings of this population-based cohort study of Ontario adolescents and adults with myocarditis or pericarditis following mRNA COVID-19 vaccination suggest that vaccine products and interdose intervals, in addition to age and sex, may be associated with the risk of myocarditis or pericarditis after receipt of these vaccines. Vaccination program strategies, such as age-based product considerations and longer interdose intervals, may reduce the risk of myocarditis or pericarditis following receipt of mRNA vaccines.