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.

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 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.

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.

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.

Pregnancy, fetal, and neonatal outcomes after a first booster dose of covid-19 vaccine during pregnancy in Ontario, Canada: population based, retrospective cohort study.

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.

Temporal trends and determinants of COVID-19 vaccine series initiation after recent 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.

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.

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.

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.

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.

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.

Temporal trends and determinants of COVID-19 vaccine coverage and series initiation during pregnancy in Ontario, Canada, December 2020 to December 2021: A population-based retrospective cohort study.

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.

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.

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.

"We need to protect each other": COVID-19 vaccination intentions and concerns among Racialized minority and Indigenous Peoples in Canada.

People may choose to receive vaccines in response to pressures that outweigh any concerns that they have. We explored Racialized minority and Indigenous Peoples' motivations for, perceptions of choice in, and concerns about, COVID-19 vaccination. We used a sequential explanatory mixed methods approach, including a national survey administered around the time vaccines were first authorized (Dec 2020) followed by qualitative interviews when vaccines were becoming more readily available to adults (May-June 2021). We analyzed survey data using descriptive statistics and interviews using critical feminist methodologies. Survey respondents self-identified as a Racialized minority (n = 1488) or Indigenous (n = 342), of which 71.4% and 64.6%, respectively, intended to receive a COVID-19 vaccine. Quantitative results indicated perceptions of COVID-19 disease were associated with vaccination intention. For instance, intention was associated with agreement that COVID-19 disease is severe, risk of becoming sick is great, COVID-19 vaccination is necessary, and vaccines available in Canada will be safe (p < 0.001). COVID-19 vaccines were in short supply in Canada when we subsequently completed qualitative interviews with a subset of Racialized minority (n = 17) and Indigenous (n = 10) survey respondents. We coded interview transcripts around three emergent themes relating to governmentality and cultural approaches to intersectional risk theories: feelings of collective responsibility, choice as privilege, and remaining uncertainties about COVID-19 vaccines. For example, some mentioned the responsibility and privilege to receive a vaccine earlier than those living outside of Canada. Some felt constraints on their freedom to choose to receive or refuse a vaccine from intersecting oppressions or their health status. Although all participants intended to get vaccinated, many mentioned uncertainties about the safety and effectiveness of COVID-19 vaccination. Survey respondents and interview participants demonstrated nuanced associations of vaccine acceptance and hesitancy shaped by perspectives of vaccine-related risks, symbolic associations of vaccines with hope, and intersecting social privileges and inequities (including racialization).

Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes.

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.

Effectiveness of COVID-19 Vaccines Over Time Prior to Omicron Emergence in Ontario, Canada: Test-Negative Design Study.

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.