Characteristics of primary care practices by proportion of patients unvaccinated against SARS-CoV-2: a cross-sectional cohort study.

BACKGROUND: Variations in primary care practices may explain some differences in health outcomes during the COVID-19 pandemic. We sought to evaluate the characteristics of primary care practices by the proportion of patients unvaccinated against SARS-CoV-2. METHODS: We conducted a population-based, cross-sectional cohort study using linked administrative data sets in Ontario, Canada. We calculated the percentage of patients unvaccinated against SARS-CoV-2 enrolled with each comprehensive-care family physician, ranked physicians according to the proportion of patients unvaccinated, and identified physicians in the top 10% (v. the other 90%). We compared characteristics of family physicians and their patients in these 2 groups using standardized differences. RESULTS: We analyzed 9060 family physicians with 10 837 909 enrolled patients. Family physicians with the largest proportion (top 10%) of unvaccinated patients (n = 906) were more likely to be male, to have trained outside of Canada, to be older, and to work in an enhanced fee-for-service model than those in the remaining 90%. Vaccine coverage (≥ 2 doses of SARS-CoV-2 vaccine) was 74% among patients of physicians with the largest proportion of unvaccinated patients, compared with 87% in the remaining patient population. Patients in the top 10% group tended to be younger and live in areas with higher levels of ethnic diversity and immigration and lower incomes. INTERPRETATION: Primary care practices with the largest proportion of patients unvaccinated against SARS-CoV-2 served marginalized communities and were less likely to use team-based care models. These findings can guide resource planning and help tailor interventions to integrate public health priorities within primary care practices.

Hepatitis C Attributable Healthcare Costs and Mortality among Immigrants: A Population-Based Matched Cohort Study.

Background: Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. Methods: We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. Results: We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6-3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: -25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Conclusions: Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.

Ongoing Gaps in the Hepatitis C Care Cascade during the Direct-Acting Antiviral Era in a Large Retrospective Cohort in Canada: A Population-Based Study.

To achieve hepatitis C virus (HCV) elimination, high uptake along the care cascade steps for all will be necessary. We mapped engagement with the care cascade overall and among priority groups in the post-direct-acting antivirals (DAAs) period and assessed if this changed relative to pre-DAAs. We created a population-based cohort of all reported HCV diagnoses in Quebec (1990-2018) and constructed the care cascade [antibody diagnosed, RNA tested, RNA positive, genotyped, treated, sustained virologic response (SVR)] in 2013 and 2018. Characteristics associated with RNA testing and treatment initiation were investigated using marginal logistic models via generalized estimating equations. Of the 31,439 individuals HCV-diagnosed in Quebec since 1990 and alive as of 2018, there was significant progress in engagement with the care cascade post- vs. pre-DAAs; 86% vs. 77% were RNA-tested, and 64% vs. 40% initiated treatment. As of 2018, a higher risk of not being RNA-tested or treated was observed among individuals born <1945 vs. >1965 [hazard ratio (HR); 95% CI; 1.35 (1.16-1.57)], those with material and social deprivation [1.21 (1.06-1.38)], and those with alcohol use disorder [1.21 (1.08-1.360]. Overall, non-immigrants had lower rates of RNA testing [0.76 (0.67-0.85)] and treatment initiation [0.63 (0.57-0.70)] than immigrants. As of 2018, PWID had a lower risk of not being RNA tested [0.67 (0.61-0.85)] but a similar risk of not being treated, compared to non-PWID. Engagement in the HCV care cascade have improved in the post-DAA era, but inequities remain. Vulnerable subgroups, including certain older immigrants, were less likely to have received RNA testing or treatment as of 2018 and would benefit from focused interventions to strengthen these steps.

Validation of case-ascertainment algorithms using health administrative data to identify people who inject drugs in Ontario, Canada.

OBJECTIVE: Health administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada. STUDY DESIGN AND SETTING: Data from cohorts of people with recent (past 12 month) injection drug use, including those participating in community-based research studies or seeking drug treatment were linked to health administrative data in Ontario from 1992-2020. We assessed the validity of algorithms to identify injection drug use over varying lookback periods (i.e., all years of data [1992 onwards] or within the past 1-5 years), including inpatient and outpatient physician billing claims for drug use, emergency department visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT). RESULTS: Algorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts, 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, emergency department visit or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity, 94.2% specificity) and recent IDU (using 3 years lookback: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment. CONCLUSION: Validated algorithms using health administrative data performed well in identifying people who inject drugs. Despite high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of injection drug use in the population in which they are applied.

A multiprovincial retrospective analysis of the incidence of myocarditis or pericarditis after mRNA vaccination compared to the incidence after SARS-CoV-2 infection.

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.

The safety of seasonal influenza vaccination among adults prescribed immune checkpoint inhibitors: A self-controlled case series study using administrative data.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of developing IRAEs among these patients given that vaccines are immunomodulatory. Previous vaccine safety studies on patients with cancer prescribed ICI therapy have demonstrated conflicting results. METHODS: Using health administrative data from Ontario, Canada among adults diagnosed with cancer who had been prescribed ICI therapy and who had received an influenza vaccine from 2012 to 2019, we conducted a self-controlled case series study. The pre-vaccination control period started 42-days post-ICI initiation until 14-days prior to vaccination, the risk period was 1-42 days post-vaccination, and the post-vaccination control period was after the risk period until ICI discontinuation or a maximum period of two years. Emergency department (ED) visit(s) and/or hospitalization for any cause after ICI initiation was used to identify severe IRAEs. We fitted a fixed-effects Poisson regression model accounting for seasonality and calendar time to estimate relative incidence of IRAEs between risk and control periods. RESULTS: We identified 1133 records of cancer patients who received influenza vaccination while prescribed ICI therapy. Most were aged ≥ 66 years (73 %), were male (63 %), had lung cancer (54 %), and had received ICI therapy with a programmed cell death protein 1(PD-1) inhibitor (91 %). A quarter (26 %) experienced an ED visit and/or hospitalization during the observation period. Rates of ED visits and/or hospitalizations in the risk vs. control periods were similar, with an incidence rate ratio of 1.04 (95 % CI: 0.75-1.45). Subgroup and sensitivity analyses yielded similar results. CONCLUSION: Seasonal influenza vaccination was not associated with an increased incidence of ED visit or hospitalization among adults with cancer treated with ICI therapy and our results support further evidence of vaccine safety.

Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

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) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 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.

Indirect impact of childhood 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian older adults: a Canadian Immunization Research Network (CIRN) retrospective observational study.

BACKGROUND: 13-valent pneumococcal conjugate vaccine (PCV13) has been part of publicly funded childhood immunisation programmes in Ontario and British Columbia (BC) since 2010. We assessed the indirect impact of infant PCV13 programmes on invasive pneumococcal disease (IPD) and all-cause pneumonia hospitalisation in older adults (aged ≥65 years) using a retrospective observational study. METHODS: We extracted monthly IPD and all-cause pneumonia cases from laboratory and health administrative databases between January 2005 and December 2018. Using a quasi-experimental difference-in-differences design, we calculated the ratio of risk ratios (RRRs) using incidence rates of IPD or all-cause pneumonia cases before (pre-PCV13 period) and after (PCV13 period) 2010 with rates of fractures as controls. RESULTS: The rates of all IPD or PCV serotype-specific IPD for older adults in both Ontario and BC did not change in 8 years after childhood PCV13 programme implementation. All-cause pneumonia increased in Ontario (RRR 1.38, 95% CI 1.11 to 1.71) but remained unchanged in BC. CONCLUSIONS: Indirect community protection of older adults from hospitalisation with pneumococcal disease stalled despite maturation of childhood PCV13 vaccination programmes in two Canadian provinces.

Protection of prior SARS-CoV-2 infection, COVID-19 boosters, and hybrid immunity against Omicron severe illness: A population-based cohort study of five million residents in Canada.

BACKGROUND: Evidence on protection of different patterns of infection- and vaccine-acquired immunity against Omicron-associated severe illness is useful in planning booster vaccination strategies. We examined protection of prior SARS-CoV-2 infection, a third or a fourth COVID-19 vaccine dose, and hybrid immunity against Omicron-associated severe illness. METHODS AND FINDINGS: This population-based cohort study followed five million individuals with at least one SARS-CoV-2 RT-PCR test before November 21, 2021 until an Omicron-associatedhospitalization or death. We used Cox regression models to estimate risks of Omicron-associated hospitalization and a composite severe outcome (hospitalized and death), among individuals with infection- and/or vaccination-acquired immunity. Individuals who were unvaccinated and had no history of a prior infection severed as the reference group. Both adjusted hazard ratios (HR) and corresponding protection (one minus adjusted HR), with 95% confidence intervals (CIs), were reported. Three doses provided 94% (95%CI 93-95) and 93% (95%CI 91-94) protection against Omicron-associated hospitalization at 2-3 and ≥3 months post-vaccination respectively, similar to the protection conferred by three doses and a prior infection (2-3 months: 99%, 95%CI 97-100; ≥3 months: 97%, 95%CI 92-99) and four doses (1 month: 87%, 95%CI 79-92; 1-2 months: 96%, 95%CI 92-98). In individuals ≥65 years old, protection of four doses increased to 95% (95%CI 91-98) at 1-2 months, significantly higher than that of three doses over the follow-up period. Similar results were observed with the composite severe outcome. CONCLUSION: At least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level.

Early influenza vaccine effectiveness estimates using routinely collected data, Alberta, Canada, 2023/24 season.

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.

Miscarriage after SARS-CoV-2 vaccination: A population-based cohort study.

OBJECTIVE: To evaluate the risk of miscarriage following SARS-CoV-2 vaccination, while accounting for the competing risk of induced abortion. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women aged 15-50 years with a confirmed pregnancy at ≤19 completed weeks' gestation. METHODS: Exposure to first SARS-CoV-2 vaccination, handled in a time-varying manner, was defined as (i) unvaccinated, (ii) remotely vaccinated >28 days before the estimated conception date or (iii) recently vaccinated ≤28 days before conception and up to 120 days after conception. MAIN OUTCOME MEASURES: The outcome was miscarriage, occurring between the estimated date of conception and up to 19 completed weeks of pregnancy. Fine-Grey hazard models, accounting for the competing risk of induced abortion, generated hazard ratios (aHR), adjusted for socio-demographic factors, comorbidities, and biweekly periods. RESULTS: Included were 246 259 pregnant women, of whom 34% received a first SARS-CoV-2 vaccination. Miscarriage occurred at a rate of 3.6 per 10 000 person-days among remotely vaccinated women and 3.2 per 10 000 person-days among those recently vaccinated, in contrast to a rate of 1.9 per 10 000 person-days among unvaccinated women, with corresponding aHR of 0.98 (95% confidence interval [CI] 0.91-1.07) and 1.00 (95% CI 0.93-1.08). CONCLUSIONS: SARS-CoV-2 vaccination was not associated with miscarriage while accounting for the competing risk of induced abortion. This study reiterates the importance of including pregnant women in new vaccine clinical trials and registries, and the rapid dissemination of vaccine safety data.

Effectiveness of mRNA COVID-19 Monovalent and Bivalent Vaccine Booster Doses Against Omicron Severe Outcomes Among Adults Aged ≥50 Years in Ontario, Canada: A Canadian Immunization Research Network Study.

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.

A Population-Based Test-Negative Matched Case-Control Analysis of SARS-CoV-2 Vaccine Effectiveness Among Pregnant People in Ontario, Canada.

OBJECTIVE: Pregnancy is a risk factor for severe SARS-CoV-2 infection, which can result in adverse pregnancy outcomes, thus making understanding vaccine effectiveness (VE) in this population important. This study aimed to assess the VE of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in pregnant people. METHODS: Population-based matched test-negative case-control study of pregnant people aged 18-49 years, of 12 or more weeks gestation in Ontario, Canada, symptomatic with possible SARS-CoV-2 infection, and having at least 1 positive (n = 1842) or negative (n = 8524) real-time polymerase chain reaction (RT-PCR) SARS-CoV-2 test between December 14, 2020, and December 31, 2021. The exposure was receipt of ≥1 dose of mRNA COVID-19 vaccine versus no vaccination. Exposure was further stratified by number and recency of doses. The primary outcome was a positive SARS-CoV-2 RT-PCR test. As a secondary outcome, VE for COVID-19-related hospitalization was assessed. RESULTS: In the primary outcome analysis, there were 1821 positive cases, matched to 1821 negative controls. The mean (SD) maternal age was 31 (5) years. When compared to those unvaccinated, receipt of ≥1 dose was associated with an estimated VE of 39% (95% CI 29%-48%) for symptomatic infection, and 85% (95% CI 72%-92%) for COVID-19 hospitalization. VE estimates demonstrated waning with increased time since last vaccination. CONCLUSIONS: mRNA COVID-19 vaccines provide protection against symptomatic COVID-19 illness and are highly effective at preventing severe illness in pregnant people. The observed effect of vaccine waning highlights the importance of booster doses to provide optimal protection for pregnant people.

Effectiveness of a Fourth COVID-19 mRNA Vaccine Dose Against the Omicron Variant in Solid Organ Transplant Recipients.

BACKGROUND: The effectiveness of booster doses of COVID-19 vaccines in solid organ transplant recipients is unclear. We conducted a population-based matched cohort study using linked administrative healthcare databases from Ontario, Canada to estimate the marginal vaccine effectiveness of a fourth versus third dose of the BNT162b2 and mRNA-1273 vaccines against clinically important outcomes (ie, hospitalization or death) and infection during the era of the Omicron variant. METHODS: We matched 3120 solid organ transplant recipients with a third COVID-19 vaccine dose (reference) to 3120 recipients with a fourth dose. Recipients were matched on the third dose date (±7 d). We used a multivariable Cox proportional hazards model to estimate the marginal vaccine effectiveness with outcomes occurring between December 21, 2021 and April 30, 2022. RESULTS: The cumulative incidence of COVID-19-related hospitalization or death was 2.8% (95% confidence interval [CI], 2.0-3.7) in the third dose group compared with 1.1% (95% CI, 0.59-1.8) in the fourth dose group after 84 d of follow-up (P < 0.001). The adjusted marginal vaccine effectiveness was 70% (95% CI, 47-83) against clinically important outcomes and 39% (95% CI, 21-52) against SARS-CoV-2 infection. CONCLUSIONS: Compared with a third dose, a fourth dose of the COVID-19 vaccine was associated with improved protection against hospitalization, death, and SARS-CoV-2 infection during the Omicron era. Results highlight the importance of a booster COVID-19 vaccine dose in solid organ transplant recipients.

Improving estimates of pertussis burden in Ontario, Canada 2010-2017 by combining validation and capture-recapture methodologies.

An underestimation of pertussis burden has impeded understanding of transmission and disallows effective policy and prevention to be prioritized and enacted. Capture-recapture analyses can improve burden estimates; however, uncertainty remains around incorporating health administrative data due to accuracy limitations. The aim of this study is to explore the impact of pertussis case definitions and data accuracy on capture-recapture estimates. We used a dataset from March 7, 2010 to December 31, 2017 comprised of pertussis case report, laboratory, and health administrative data. We compared Chao capture-recapture abundance estimates using prevalence, incidence, and adjusted false positive case definitions. The latter was developed by removing the proportion of false positive physician billing code-only case episodes after validation. We calculated sensitivity by dividing the number of observed cases by abundance. Abundance estimates demonstrated that a high proportion of cases were missed by all sources. Under the primary analysis, the highest sensitivity of 78.5% (95% CI 76.2-80.9%) for those less than one year of age was obtained using all sources after adjusting for false positives, which dropped to 43.1% (95% CI 42.4-43.8%) for those one year of age or older. Most code-only episodes were false positives (91.0%), leading to considerably lower abundance estimates and improvements in laboratory testing and case report sensitivity using this definition. Accuracy limitations can be accounted for in capture-recapture analyses using different case definitions and adjustment. The latter enhanced the validity of estimates, furthering the utility of capture-recapture methods to epidemiological research. Findings demonstrated that all sources consistently fail to detect pertussis cases. This is differential by age, suggesting ascertainment and testing bias. Results demonstrate the value of incorporating real time health administrative data into public health surveillance if accuracy limitations can be addressed.

What are effective vaccine distribution approaches for equity-deserving and high-risk populations during COVID-19? Exploring best practices and recommendations in Canada: protocol for a mixed-methods multiple case codesign study.

INTRODUCTION: The WHO has stated that vaccine hesitancy is a serious threat to overcoming COVID-19. Vaccine hesitancy among underserved and at-risk communities is an ongoing challenge in Canada. Public confidence in vaccine safety and effectiveness and the principles of equity need to be considered in vaccine distribution. In Canada, governments of each province or territory manage their own healthcare system, providing an opportunity to compare and contrast distribution strategies. The overarching objective of this study is to identify effective vaccine distribution approaches and advance knowledge on how to design and implement various strategies to meet the different needs of underserved communities. METHODS AND ANALYSIS: Multiple case studies in seven Canadian provinces will be conducted using a mixed-methods design. The study will be informed by Experience-Based CoDesign techniques and theoretically guided by the Socio-Ecological Model and the Vaccine Hesitancy Matrix frameworks. Phase 1 will involve a policy document review to systematically explore the vaccine distribution strategy over time in each jurisdiction. This will inform the second phase, which will involve (2a) semistructured, in-depth interviews with policymakers, public health officials, researchers, providers, groups representing patients, researchers and stakeholders and (2b) an analysis of population-based administrative health data of vaccine administration. Integration of qualitative and quantitative data will inform the identification of effective vaccine distribution approaches for various populations. Informed by this evidence, phase 3 of the study will involve conducting focus groups with multiple stakeholders to codesign recommendations for the design and implementation of effective vaccine delivery strategies for equity-deserving and at-risk populations. ETHICS AND DISSEMINATION: This study is approved by the University of Toronto's Health Sciences Research Ethics Board (#42643), University of British Columbia Behavioural Research Ethics Board (#H22-01750-A002), Research Ethics Board of the Nova Scotia Health Authority (#48272), Newfoundland and Labrador Health Research Ethics Board (#2022.126), Conjoint Health Research Ethics Board, University of Calgary (REB22-0207), and University of Manitoba Health Research Board (H2022-239). The outcome of this study will be to produce a series of recommendations for implementing future vaccine distribution approaches from the perspective of various stakeholders, including equity-deserving and at-risk populations.

Protection conferred by COVID-19 vaccination, prior SARS-CoV-2 infection, or hybrid immunity against Omicron-associated severe outcomes among community-dwelling adults.

INTRODUCTION: We assessed protection from COVID-19 vaccines and/or prior 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, PCR-tested adults aged ≥50 years in Ontario, Canada between January 2, 2022 and June 30, 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%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. CONCLUSION: 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.

Effectiveness of maternal influenza vaccination during pregnancy against laboratory-confirmed seasonal influenza among infants under 6 months of age in Ontario, Canada.

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 2010-2019 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, 1,783 (7.5%) were positive and 1,708 (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 (1st/2nd: 66%, 40%-80%; 3rd: 63%, 46%-74%), infant age at testing (0-<2 months: 63%, 46%-75%; 2-<6 months: 64%, 36%-79%), and gestational age at birth (≥37 weeks: 64%, 50%-75%; < 37 weeks: 61%, 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.

Newborn and Early Infant Outcomes Following Maternal COVID-19 Vaccination During Pregnancy.

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.