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.

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.

Effectiveness and Duration of Protection of a Fourth Dose of Coronavirus Disease 2019 Messenger RNA Vaccine Among Long-term Care Residents in Ontario, Canada.

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.

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.

Leukemia: What Primary Care Physicians Need to Know.

Leukemia is caused by an abnormal proliferation of hematopoietic stem cells in the bone marrow. The four general subtypes are acute lymphoblastic, acute myelogenous, chronic lymphocytic, and chronic myelogenous. Acute lymphoblastic leukemia primarily occurs in children, whereas the other subtypes are more common in adults. Risk factors include certain chemical and ionizing radiation exposures and genetic disorders. Common symptoms include fever, fatigue, weight loss, joint pain, and easy bruising or bleeding. Diagnosis is confirmed with bone marrow biopsy or peripheral blood smear. Hematology-oncology referral is recommended in patients with suspected leukemia. Chemotherapy, radiation, targeted molecular therapy, monoclonal antibodies, or hematopoietic stem cell transplantation are common treatments. Complications from treatment include serious infections from immunosuppression, tumor lysis syndrome, cardiovascular events, and hepatotoxicity. Long-term sequelae in leukemia survivors include secondary malignancies, cardiovascular disease, and musculoskeletal and endocrine disorders. Five-year survival rates are highest in younger patients and those diagnosed with chronic myelogenous or chronic lymphocytic leukemia.

Association of COVID-19 Vaccination in Pregnancy With Adverse Peripartum Outcomes.

Importance: There is limited comparative epidemiological evidence on outcomes associated with COVID-19 vaccination during pregnancy; monitoring pregnancy outcomes in large populations is required. Objective: To evaluate peripartum outcomes following COVID-19 vaccination during pregnancy. Design, Setting, and Participants: Population-based retrospective cohort study in Ontario, Canada, using a birth registry linked with the provincial COVID-19 immunization database. All births between December 14, 2020, and September 30, 2021, were included. Exposures: COVID-19 vaccination during pregnancy, COVID-19 vaccination after pregnancy, and no vaccination. Main Outcomes and Measures: Postpartum hemorrhage, chorioamnionitis, cesarean delivery (overall and emergency cesarean delivery), admission to neonatal intensive care unit (NICU), and low newborn 5-minute Apgar score (<7). Linear and robust Poisson regression was used to generate adjusted risk differences (aRDs) and risk ratios (aRRs), respectively, comparing cumulative incidence of outcomes in those who received COVID-19 vaccination during pregnancy with those vaccinated after pregnancy and those with no record of COVID-19 vaccination at any point. Inverse probability of treatment weights were used to adjust for confounding. Results: Among 97 590 individuals (mean [SD] age, 31.9 [4.9] years), 22 660 (23%) received at least 1 dose of COVID-19 vaccine during pregnancy (63.6% received dose 1 in the third trimester; 99.8% received an mRNA vaccine). Comparing those vaccinated during vs after pregnancy (n = 44 815), there were no significantly increased risks of postpartum hemorrhage (incidence: 3.0% vs 3.0%; aRD, -0.28 per 100 individuals [95% CI, -0.59 to 0.03]; aRR, 0.91 [95% CI, 0.82-1.02]), chorioamnionitis (0.5% vs 0.5%; aRD, -0.04 per 100 individuals [95% CI, -0.17 to 0.09]; aRR, 0.92 [95% CI, 0.70-1.21]), cesarean delivery (30.8% vs 32.2%; aRD, -2.73 per 100 individuals [95% CI, -3.59 to -1.88]; aRR, 0.92 [95% CI, 0.89-0.95]), NICU admission (11.0% vs 13.3%; aRD, -1.89 per 100 newborns [95% CI, -2.49 to -1.30]; aRR, 0.85 [95% CI, 0.80-0.90]), or low Apgar score (1.8% vs 2.0%; aRD, -0.31 per 100 newborns [95% CI, -0.56 to -0.06]; aRR, 0.84 [95% CI, 0.73-0.97]). Findings were qualitatively similar when compared with individuals who did not receive COVID-19 vaccination at any point (n = 30 115). Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination, was not significantly associated with increased risk of adverse peripartum outcomes. Study interpretation should consider that the vaccinations received during pregnancy were primarily mRNA vaccines administered in the second and third trimester.

Characteristics Associated With Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Ontario, Canada: A Cohort Study.

BACKGROUND: Within-household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been identified as one of the main sources of spread of coronavirus disease 2019 (COVID-19) after lockdown restrictions and self-isolation guidelines are implemented. Secondary attack rates among household contacts are estimated to be 5-10 times higher than among non-household contacts, but it is unclear which individuals are more prone to transmit infection within their households. METHODS: Using address matching, a cohort was assembled of all individuals with laboratory-confirmed COVID-19 residing in private households in Ontario, Canada. Descriptive analyses were performed to compare characteristics of cases in households that experienced secondary transmission versus those that did not. Logistic regression models were fit to determine index case characteristics and neighborhood characteristics associated with transmission. RESULTS: Between January and July 2020, there were 26 714 individuals with COVID-19 residing in 21 226 households. Longer testing delays (≥5 vs 0 days; odds ratio [OR], 3.02; 95% confidence interval [CI], 2.53-3.60) and male gender (OR, 1.28; 95% CI, 1.18-1.38) were associated with greater odds of household secondary transmission, while being a healthcare worker (OR, .56; 95% CI, .50-.62) was associated with lower odds of transmission. Neighborhoods with larger average family size and a higher proportion of households with multiple persons per room were also associated with greater odds of transmission. CONCLUSIONS: It is important for individuals to get tested for SARS-CoV-2 infection as soon as symptoms appear, and to isolate away from household contacts; this is particularly important in neighborhoods with large family sizes and/or crowded households.

Incidence of Hospitalizations and Emergency Department Visits for Herpes Zoster in Immunocompromised and Immunocompetent Adults in Ontario, Canada, 2002-2016.

BACKGROUND: Immunocompromised adults are at .increased risk of herpes zoster (HZ) infection and related complications. We aimed to assess the incidence of hospital-attended HZ (ie, seen in hospital or emergency department) in immunocompromised populations and compare it to immunocompetent populations. METHODS: We calculated incidence rates (IRs) of hospital-attended HZ in Ontario, Canada, between 1 April 2002 and 31 August 2016 in adults ≥18 years of age categorized as immunocompromised or immunocompetent. We repeated these analyses by type of immunocompromising condition and provided incidence rate ratios (IRRs) comparing to immunocompetent adults. We also calculated IRs and IRRs of HZ complications by immunocompromised status. RESULTS: There were 135 206 incident cases of hospital-attended HZ during the study period. Immunocompromised adults accounted for 13% of these cases despite representing 3% of the population. The risk of hospital-attended HZ was higher for immunocompromised adults compared with immunocompetent adults (IRR, 2.9 [95% confidence interval {CI}, 2.9-3.0]) and ranged across type of immunocompromising conditions, from 2.6 (95% CI, 2.6-2.7) in those with a solid tumor malignancy to 12.3 (95% CI, 11.3-13.2) in those who had undergone hematopoietic stem cell transplant. The risk of any HZ complication was higher in immunocompromised adults (IRR, 3.6 [95% CI, 3.5-3.7]) and highest for disseminated zoster (IRR, 32.8 [95% CI, 27.8-38.6]). CONCLUSIONS: The risk of hospital-attended HZ and related complications was higher in immunocompromised populations compared with immunocompetent populations. Our findings underscore the high-risk nature of this population and the potential benefits that may be realized through HZ vaccination.

Global travel patterns and risk of measles in Ontario and Quebec, Canada: 2007-2011.

BACKGROUND: In 2011 the largest measles outbreak in North America in a decade occurred in Quebec, Canada with over 700 cases. In contrast, measles activity in neighbouring province Ontario remained low (8 cases). Our objective was to determine the extent to which the difference could be explained by differing travel patterns. METHODS: We explored the relationship between measles cases over 2007-2011, by importation classification, in Quebec and Ontario in relation to global travel patterns to each province using an ecological approach. Global measles exposure was estimated by multiplying the monthly traveler volume for each country of origin into Quebec or Ontario by the yearly measles incidence rate for the corresponding country. Visual inspection of temporal figures and calculation of Pearson correlation coefficients were performed. RESULTS: Global measles exposure was similar in Ontario and Quebec. In Quebec, there was a nearly perfectly linear relationship between annual measles cases and its global measles exposure index over 2007-2011 (r = 0.99, p = 0.001). In contrast, there was a non-significant association in Ontario. The 2011 rise in Quebec's index was largely driven by a dramatic increase in measles activity in France the same year. CONCLUSIONS: Global measles activity was associated with measles epidemiology in Quebec. Global measles exposure risk is higher in Ontario than Quebec. Differences in measles epidemiology between Ontario and Quebec from 2007-2011 are not explained by greater exposure in Quebec. A combination of alternative factors may be responsible, including differences in population susceptibility.

Invasive Pneumococcal Disease Epidemiology and Serotype Replacement After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Ontario, Canada, 2007-2022.

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.

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.

Pharmacokinetics of mavacoxib in New Zealand White rabbits (Oryctolagus cuniculus).

OBJECTIVES: To characterize the pharmacokinetics of a single oral dose (6 mg/kg) of mavacoxib in New Zealand White rabbits (Oryctolagus cuniculus) and to characterize any clinicopathologic effects with this medication and dose. ANIMALS: Six healthy, 4-month-old New Zealand White rabbits (3 male, 3 female). PROCEDURES: Before drug administration, clinicopathologic samples were collected for baseline data (CBC, serum biochemical analyses, and urinalysis including urine protein-to-creatinine ratio). All 6 rabbits received a single oral dose (6 mg/kg) of mavacoxib. Clinicopathologic samples were collected at set time intervals to compare with the baseline. Plasma mavacoxib concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using non-compartmental methods. RESULTS: After a single oral dose, the maximum plasma concentration (Cmax; mean, range) was 854 (713-1040) ng/mL, the time to Cmax (tmax) was 0.36 (0.17-0.50) days, the area under the curve from 0 to the last measured time point (AUC0-last) was 2000 (1765-2307) days*ng/mL, the terminal half-life (t1/2) was 1.63 (1.30-2.26) days, and the terminal rate constant (λz) was 0.42 (0.31-0.53) days. All results for CBCs, serum biochemical analyses, urinalyses, and urine protein-to-creatinine ratios remained within published normal reference intervals. CLINICAL RELEVANCE: This study determined that plasma concentrations reached target levels of 400 ng/mL for 48 hours in 3/6 rabbits at 6 mg/kg PO. In the remaining 3/6 rabbits, the plasma concentrations were 343-389 ng/mL at 48 hours, which is below the target concentration. Further research is needed to make a dosing recommendation, including a pharmacodynamic study and investigating pharmacokinetics at different doses and multiple doses.

Methodological changes implemented over time to support accurate and timely COVID-19 vaccine coverage estimates: Ontario, Canada.

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.

Myocarditis or Pericarditis Events After BNT162b2 Vaccination in Individuals Aged 12 to 17 Years in Ontario, Canada.

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.

COVID-19 Vaccine Effectiveness Against Omicron Infection and Hospitalization.

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.

Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes.

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.