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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.

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.

ObjectiveWe 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.MethodsWe used a test-negative design to estimate vaccine effectiveness (VE), with unvaccinated adults as the comparator, against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years between June 19, 2022 and January 28, 2023 stratified by time since vaccination. We explored VE by vaccine product (Moderna Spikevax®monovalent; Pfizer-BioNTech Comirnaty®monovalent; Moderna Spikevax®BA.1 bivalent; Pfizer-BioNTech Comirnaty®BA.4/BA.5 bivalent).ResultsWe included 3,755 Omicron cases and 14,338 test-negative controls. For the Moderna and Pfizer-BioNTech monovalent vaccines, VE 7-29 days after vaccination was 85% (95% confidence interval [CI], 72-92%) and 88% (95%CI, 82-92%), respectively, and was 82% (95%CI, 76-87%) and 82% (95%CI, 77-86%) 90-119 days after vaccination. For the Moderna BA.1 bivalent vaccine, VE was 86% (95%CI, 82-90%) 7-29 days after vaccination and was 76% (95%CI, 66-83%) 90-119 days after vaccination. For the Pfizer-BioNTech BA.4/BA.5 bivalent vaccine, VE 7-29 days after vaccination was 83% (95%CI, 77-88%) and was 81% (95%CI 72-87%) 60-89 days after vaccination.ConclusionsBooster doses of monovalent and bivalent mRNA COVID-19 vaccines provided similar, strong initial protection against severe outcomes in community-dwelling adults aged ≥50 years in Ontario. Nonetheless, uncertainty remains around waning protection of these vaccines.

BackgroundBackground incidence rates are critical in pharmacovigilance to facilitate identification of vaccine safety signals. We estimated background incidence rates of nine adverse events of special interest related to COVID-19 vaccines in Ontario, Canada.MethodsWe conducted a population-based retrospective observational study using linked health administrative databases for hospitalizations and emergency department visits among Ontario residents. We estimated incidence rates of Bell’s palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barré syndrome, and transverse myelitis during five pre-pandemic years (2015– 2019) and 2020.ResultsThe average annual population was 14 million across all age groups with 51% female. The pre-pandemic mean annual rates per 100,000 population during 2015–2019 were 43.9 for idiopathic thrombocytopenia, 27.8 for Bell’s palsy, 25.0 for febrile convulsions, 22.8 for acute disseminated encephalomyelitis, 11.3 for myocarditis/pericarditis, 8.6 for pericarditis, 2.9 for myocarditis, 1.9 for Guillain-Barré syndrome, 1.7 for transverse myelitis, and 1.6 for Kawasaki disease. Females had higher rates of acute disseminated encephalomyelitis and transverse myelitis while males had higher rates of myocarditis, pericarditis, and Guillain-Barré syndrome. Bell’s palsy, acute disseminated encephalomyelitis, and Guillain-Barré syndrome increased with age. The mean rates of myocarditis and/or pericarditis increased with age up to 79 years; males had higher rates than females: from 12–59 years for myocarditis and ≥12 years for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age.ConclusionsOur estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Background Vaccinating children (≤17 years old) is important for controlling the COVID-19 pandemic. As parents are primary decision makers for their children, we aimed to assess parents’ perceptions and intentions regarding COVID-19 vaccination for their children, including for some underserved populations (e.g., newcomers, Indigenous peoples, and visible minority groups). Methods We conducted a cross-sectional national survey of Canadian parents in December 2020, just as COVID-19 vaccines were approved for adults, to assess intention to vaccinate their children (aged 0–17 years) against COVID-19, perceptions of COVID-19 disease and vaccines, previous uptake of influenza and routine vaccines, and sociodemographic characteristics. Binomial logistic regression was used to assess the association between parents' lack of COVID-19 vaccination intention for their children and various independent variables. Results Sixty-three percent of parents (1074/1702) intended to vaccinate their children against COVID-19. Those employed part-time (compared to full-time) had lower intention to vaccinate their children (aOR = 1.73, 95% CI: 1.06–2.84), while those who spoke languages other than English, French, or Indigenous languages were less likely to have low intention (aOR = 0.55, 95% CI: 0.32–0.92). Low vaccination intention was also associated with children not receiving influenza vaccine pre-pandemic (aOR = 1.51, 95% CI: 1.04–2.21), parents having low intention to vaccinate themselves against COVID-19 (aOR = 9.22, 95% CI: 6.43–13.34), believing COVID-19 vaccination is unnecessary (aOR = 2.59, 95% CI: 1.72–3.91) or unsafe (aOR = 4.21, 95% CI: 2.96–5.99), and opposing COVID-19 vaccine use in children without prior testing (aOR = 3.09, 95% CI: 1.87–5.24). Interpretation Parents’ COVID-19 vaccination intentions for their children are better predicted by previous decisions regarding influenza vaccination than routine childhood vaccines, and other perceptions of COVID-19 vaccine-related factors. Public communication should highlight the safety and necessity of COVID-19 vaccination in children to support a return to normal activities. Further research should assess actual COVID-19 vaccination uptake in children, particularly for underserved populations.

We estimated the effectiveness of a fourth dose of mRNA COVID-19 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.

BackgroundAs of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine ≥84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant. Seven months have passed since fourth doses were implemented, allowing for the examination of fourth dose protection over time.MethodsWe used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged ≥60 years who were tested for SARS-CoV-2 between December 30, 2021 and August 3, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death).ResultsWe included 21,275 Omicron cases and 273,466 test-negative controls. The marginal effectiveness of a fourth dose ConclusionsOur findings suggest that fourth doses of mRNA COVID-19 vaccines provide additional protection against Omicron-related outcomes in LTC residents, but the protection wanes over time, with more waning seen against infection than severe outcomes.

ImportanceThe 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresReceipt of 2 or 3 doses of the COVID-19 vaccine and time since last dose.Main Outcomes and MeasuresThe 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%.ResultsOf 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 RelevanceIn 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.

ImportanceThe 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).ObjectiveTo 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 ParticipantsThis 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.ExposureReceipt of BNT162b2 (Comirnaty [Pfizer-BioNTech]) vaccine.Main Outcomes and MeasureReported 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.ResultsThere 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 RelevanceResults 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.

POINTS CLES Une personne indienne de 69 ans en visite au Canada est venue consulter a l’hopital pour une detresse respiratoire aigue 48 heures apres son arrivee au pays. Elle a signale qu’au moment de son depart de l’Inde, elle avait des maux de gorge, la voix enrouee et une toux se

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.

Background In Ontario, Canada, little is currently known about the extent to which un-immunized children may cluster geographically. Our objectives were to: describe the geographic distribution of fully un-immunized children; identify geographic clusters (hotspots) of un-immunized children; and to characterize the contribution of spatial effects and covariates on hotspots, where found. Methods Our analytic cohort consisted of Ontario students aged 7–17 years in the 2016–2017 school year. We defined students as un-immunized if they had zero doses of any vaccine and a non-medical exemption recorded in Ontario’s registry. We calculated unadjusted proportions of un-immunized students by Census Subdivision (CSD) and then used a sequential approach to identify hotspots starting first with hotspot identification at the CSD level and then probed identified hotspots further by Dissemination Area (DA) and including covariates. Hotspots were identified using the Besag-York-Mollie Bayesian spatial model and were defined as areas with >95% probability of having two times the proportion of un-immunized students, relative to the province overall. Results We identified 15,208 (0.94%) un-immunized children within our cohort consisting of more than 1.61 million students. Unadjusted proportions of un-immunized students varied greatly by geography, ranging from 0% to 21.5% by CSD. We identified 16 hotspot CSDs which clustered in five distinct areas, all of which were located in southern Ontario. The contribution of covariates and spatial effects on the risk of having un-immunized students varied greatly across hotspot areas. Conclusions Although the provincial proportion (0.94%) of un-immunized students is small, geographical clustering of such students is evident in Ontario and in some areas presents an important risk for future outbreaks. Further qualitative work within these hotspot areas would be a helpful next step to better characterize the factors associated with vaccine refusal in these communities.

KEY POINTS A 69-year-old visitor to Canada from India presented to hospital with acute respiratory distress 48 hours after arrival. The patient reported sore throat, hoarse voice and dry cough, which had developed on departure from India and progressed over 48 hours to shortness of breath, fever and

BackgroundAs of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine ≥84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant.MethodsWe used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged ≥60 years who were tested for SARS-CoV-2 between December 30, 2021 and April 27, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death).ResultsWe included 13,654 Omicron cases and 205,862 test-negative controls. The marginal effectiveness of a fourth dose (with 95% of fourth dose vaccine recipients receiving mRNA-1273) ≥7 days after vaccination versus a third dose received ≥84 days prior was 19% (95% Confidence Interval [CI], 12-26%) against infection, 31% (95%CI, 20-41%) against symptomatic infection, and 40% (95%CI, 24-52%) against severe outcomes. VE (compared to an unvaccinated group) increased with each additional dose, and for a fourth dose was 49% (95%CI, 43-54%), 69% (95%CI, 61-76%), and 86% (95%CI, 81-90%), against infection, symptomatic infection, and severe outcomes, respectively.ConclusionsOur findings suggest that compared to a third dose received ≥84 days ago, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes caused by Omicron among long-term care residents. Compared to unvaccinated individuals, fourth doses provide strong protection against severe outcomes, but the duration of protection remains unknown.

IntroductionData on vaccine effectiveness (VE) against Omicron in adolescents are limited. We estimated 2-dose and 3-dose VE against Omicron and Delta in adolescents aged 12-17 years in Ontario, Canada.MethodsWe conducted a test-negative design study among SARS-CoV-2-tested adolescents aged 12-17 years between November 22, 2021 (date of first Omicron detection) and March 6, 2022; we assessed Delta outcomes prior to January 2, 2022. We used multivariable logistic regression to compare the odds of vaccination in cases to symptomatic test-negative controls and calculated VE as 1-adjusted odds ratio.ResultsVE was lower against symptomatic Omicron infection than against Delta and decreased more rapidly over time, from 51% (95%CI, 38-61%) in the 7-59 days following a second dose to 29% (95%CI, 17-38%) after 180 days, compared to 97% (95%CI, 94-99%) and 90% (95%CI, 79-95%) for the same intervals against symptomatic Delta infection. Overall, 2-dose VE against severe outcomes caused by Omicron was 85% (95%CI, 74-91%) ≥7 days following a second dose and estimates were similar over time. VE against symptomatic Omicron infection was 62% (95%CI, 49-72%) ≥7 days following a third dose.DiscussionTwo-dose VE against symptomatic Omicron infection wanes over time in adolescents. While lower than observed against Delta, protection against severe outcomes appears to be maintained over time. A third dose substantially improves protection against Omicron infection, but 3-dose VE is only moderate at approximately 60% in the early period following vaccination and the duration of this protection is unknown.

Objectives Describe Ontario's school-based human papillomavirus (HPV) vaccination program from the perspective of local public health units (PHUs). Methods In 2018, Vaccine Preventable Diseases (VPD) managers at each of Ontario's 35 PHUs were invited to participate in an online survey regarding the organization and delivery of their HPV vaccination program. Questions were asked on the school-based program, training and support of vaccine providers, communication and promotion, assessing coverage rates and perceptions of the program's strengths and challenges. Descriptive statistics were generated for close-ended items. A thematic content analysis was performed for open-ended items. Results Eighteen PHUs (54%, n = 19/35) responded. All responding PHUs provided the HPV vaccine in publicly funded schools but only 6 reported being permitted to provide HPV vaccine in private schools. Fact sheets, Q&As or other written information locally developed by the PHUs were the main tools used to communicate with parents (n = 17), students (n = 13), school personnel (n = 13) and school board officials (n = 9). The most frequently reported barriers were: limited program resources, negative perceptions held by parents and/or school staff regarding the HPV vaccine, logistical issues (e.g., getting the consents forms returned, collaboration with schools for vaccine delivery) and the fact that HPV vaccination is not mandatory under Ontario legislation. Conclusion Local public health units that implement HPV vaccine programs in schools identified logistical barriers, public perceptions about the HPV vaccine and the voluntary nature of the program as the main barriers.

Introduction In Ontario, Canada, parents have the responsibility to report their child’s routine infant and childhood vaccines to the provincial immunization registry (the Digital Health Immunization Repository; DHIR) without healthcare provider validation. Despite its use in routine immunization coverage monitoring, no study has previously examined the completeness of immunization data within the DHIR. Methods We assessed the completeness of DHIR immunizations, as compared to immunizations within the Electronic Medical Records—Primary Care (EMRPC) database, also known as EMRALD, a network of family physician electronic medical records (EMRs). We linked client records from the DHIR and EMRPC to a centralized population file. To create the study cohort, we examined children born during 2005–2008 and further defined the cohort based on those rostered to an EMRPC physician, visit criteria to ensure ongoing care by an EMRPC provider, and school attendance in Ontario at age 7. We calculated up-to-date (UTD) immunization coverage at age 7 for individual vaccines and overall using data from the DHIR and EMRPC separately, and compared the estimates. Results The analytic cohort to assess DHIR data completeness included 2,657 children. Overall UTD coverage (all vaccines assessed) was 82.0% in the DHIR and 67.6% in EMRPC. UTD coverage was higher in the DHIR for all vaccines assessed individually, with the exception of meningococcal C conjugate vaccine (difference = 0.3%). After excluding two EMRPC sites with irregularities in immunization data, the difference in overall UTD coverage between systems decreased from 14.4% to 6.6% Interpretation These results validate the use of DHIR for coverage assessment but also suggest that bidirectional exchange of immunization information has the potential to increase immunization data completeness in both systems.

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 (

BackgroundThere is a paucity of data on the burden of the full spectrum of community-acquired pneumonia (CAP) and acute otitis media (AOM) from outpatient and inpatient settings across the age spectrum.MethodsWe conducted a population-based retrospective study in Ontario and British Columbia (BC), Canada, to estimate the incidence rate of CAP and AOM in children and adults over a 14-year period using health administrative databases. CAP and AOM cases were identified from outpatient physician consultation and hospitalisation data in both provinces, and from emergency department visit data in Ontario.ResultsDuring 2005–2018, Ontario had 3 607 124 CAP, 172 290 bacterial CAP, 7814 pneumococcal pneumonia, and 8 026 971 AOM cases. The incidence rate of CAP declined from 3077/100 000 in 2005 to 2604/100 000 in 2010 before increasing to 2843/100 000 in 2018; bacterial CAP incidence rate also declined from 178/100 000 in 2005 to 112/100 000 in 2010 before increasing to 149/100 000 in 2018. The incidence rate of AOM decreased from 4192/100 000 in 2005 to 3178/100 000 in 2018. BC had 970 455 CAP, 317 913 bacterial CAP, 35 287 pneumococcal pneumonia and 2 022 871 AOM cases. The incidence rate of CAP in BC decreased from 2214/100 000 in 2005 to 1964/100 000 in 2010 before increasing to 2176/100 000 in 2018; bacterial CAP incidence rate increased from 442/100 000 in 2005 to 981/100 000 in 2018. The incidence rate of AOM decreased from 3684/100 000 in 2005 to 2398/100 000 in 2018. The incidence rate of bacterial CAP increased with age in older adults (≥65 years) with the highest burden in the oldest cohort aged ≥85 years both before and after 13-valent pneumococcal conjugate vaccine (PCV13) programme in both provinces. Hospitalised pneumococcal pneumonia decreased slightly but non-hospitalised pneumococcal pneumonia increased in BC during PCV13 period. No consistent direct benefit of PCV13 on CAP was observed in the paediatric population.ConclusionsThere is a substantial burden of CAP and AOM in Ontario and BC. Indirect benefits from childhood PCV vaccination and polysaccharide vaccination of older adults have not substantially decreased the burden of pneumococcal pneumonia in older adults.

BackgroundThe incidence of SARS-CoV-2 infection, including among those who have received 2 doses of COVID-19 vaccines, increased substantially following the emergence of Omicron in Ontario, Canada.MethodsApplying the test-negative study design to linked provincial databases, we estimated vaccine effectiveness (VE) against symptomatic infection and severe outcomes (hospitalization or death) caused by Omicron or Delta between December 6 and 26, 2021. We used multivariable logistic regression to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose, compared to unvaccinated individuals.ResultsWe included 16,087 Omicron-positive cases, 4,261 Delta-positive cases, and 114,087 test-negative controls. VE against symptomatic Delta infection declined from 89% (95%CI, 86-92%) 7-59 days after a second dose to 80% (95%CI, 74-84%) after ≥240 days, but increased to 97% (95%CI, 96-98%) ≥7 days after a third dose. VE against symptomatic Omicron infection was only 36% (95%CI, 24-45%) 7-59 days after a second dose and provided no protection after ≥180 days, but increased to 61% (95%CI, 56-65%) ≥7 days after a third dose. VE against severe outcomes was very high following a third dose for both Delta and Omicron (99% [95%CI, 98-99%] and 95% [95%CI, 87-98%], respectively).ConclusionsIn contrast to high levels of protection against both symptomatic infection and severe outcomes caused by Delta, our results suggest that 2 doses of COVID-19 vaccines only offer modest and short-term protection against symptomatic Omicron infection. A third dose improves protection against symptomatic infection and provides excellent protection against severe outcomes for both variants.

SUMMARYMany species throughout the animal kingdom naturally regenerate complex body parts following amputation. Most research in appendage regeneration has focused on identifying mechanisms that influence cell behaviors in the remaining stump tissue, immediately adjacent to the injury site. Roles for activation steps that occur outside of the injury site remain largely unexplored, yet they may be critical for successful regeneration. Here, we discovered a role for adrenaline in stimulating a body-wide stem cell activation response to amputation that drives limb regeneration. Notably, this systemic response is mediated by engagement of the peripheral nervous system (PNS) and adrenergic signaling at both the injury site and in distant, uninjured tissues. This work challenges the predominant conceptual framework considering the injury site alone in the regenerative response, arguing instead for body-wide stem cell activation as a priming step upon which molecular cues at the injury site then build tissue.

Post-licensure adverse events following immunization (AEFI) surveillance is conducted to monitor vaccine safety, such as identifying batch/brand issues and rare reactions, which consequently improves community confidence. The integration of technology has been proposed to improve AEFI surveillance, however, there is an absence of description regarding which digital solutions are successfully being used and their unique characteristics.The objectives of this scoping review were to 1) map the research landscape on digital systems used for active, participant-centred, AEFI surveillance and 2) describe their core components.We conducted a scoping review informed by the PRISMA Extension for Scoping Reviews (PRSIMA-ScR) guideline. OVID-Medline, Embase Classic + Embase, and Medrxiv were searched by a medical librarian from January 1, 2000 to January 28th, 2021. Two independent reviewers determined which studies met inclusion based on pre-specified eligibility criteria. Data extraction was conducted using pre-made tables with specific variables by one investigator and verified by a second.Twenty-seven publications met inclusion, the majority of which came from Australia (n = 15) and Canada (n = 6). The most studied active, participant-centred, digital AEFI surveillance systems were SmartVax (n = 8) (Australia), Vaxtracker (n = 7) (Australia), and Canadian National Vaccine Safety (CANVAS) Network (Canada) (n = 6). The two most common methods of communicating with vaccinees reported were short-message-service (SMS) (n = 15) and e-mail (n = 14), with online questionnaires being the primary method of data collection (n = 20).Active, participant-centred, digital AEFI surveillance is an area actively being researched as depicted by the literature landscape mapped by this scoping reviewWe hypothesize that the AEFI surveillance approach herein described could become a primary method of collecting self-reported subjective symptoms and reactogenicity from vaccinees, complementing existing systems. Future evaluation of identified digital solutions is necessary to bring about improvements to current vaccine surveillance systems to meet contemporary and future public health needs.

ImportanceIncreased rates of myocarditis/pericarditis following COVID-19 mRNA vaccines have been observed. However, little data are available related to product-specific differences, which have important programmatic impacts.ObjectiveThe objective of this study was to estimate reporting rates of myocarditis/pericarditis following COVID-19 mRNA vaccine by product, age, sex, and dose number, as well inter-dose interval.DesignWe conducted a population-based cohort study using passive vaccine safety surveillance data. All individuals in Ontario, Canada who received at least one dose of COVID-19 mRNA vaccine between December 14, 2020 and September 4, 2021 were included.SettingThis study was conducted in Ontario, Canada (population: 14.7 million) using the provincial COVID-19 vaccine registry and provincial adverse events following immunization database.ParticipantsWe included all individuals with a reported episode of myocarditis/pericarditis following COVID-19 vaccine in the study period. We obtained information on all doses administered in the province to calculate reporting rates.ExposureReceipt of COVID-19 mRNA vaccine (mRNA-1273 [Moderna Spikevax] or BNT162b2 [Pfizer-BioNTech Comirnaty]).Main Outcome(s) and Measure(s)Reported rate of myocarditis/pericarditis meeting level 1-3 of the Brighton Collaboration case definitions.ResultsThere were 19,740,741 doses of mRNA vaccines administered and 297 reports of myocarditis/pericarditis meeting our inclusion criteria. Among these, 69.7% occurred following the second dose of COVID-19 mRNA vaccine and 76.8% occurred in males. The median age of individuals with a reported event was 24 years. The highest reporting rate of myocarditis/pericarditis was observed in males aged 18-24 years following mRNA-1273 as the second dose; the rate in this age group was 5.1 (95% CI 1.9-15.5) times higher than the rate following BNT162b2 as the second dose. Overall reporting rates were higher when the inter-dose interval was shorter (i.e., ≤30 days) for both vaccine products. Among individuals who received mRNA-1273 for the second dose, rates were higher for those who had a heterologous as opposed to homologous vaccine schedule.Conclusions and RelevanceOur results suggest that vaccine product, inter-dose interval and vaccine schedule combinations may play a role in the risk of myocarditis/pericarditis, in addition to age and sex. Certain programmatic strategies could reduce the risk of myocarditis/pericarditis following mRNA vaccines.

To investigate COVID-19 vaccine uptake and intent among pregnant people in Canada, and determine associated factors.We conducted a national cross-sectional survey among pregnant people from May 28 through June 7, 2021 (n = 193). Respondents completed a questionnaire to determine COVID-19 vaccine acceptance (defined as either received or intend to receive a COVID-19 vaccine during pregnancy), factors associated with vaccine acceptance, and rationale for accepting/not accepting the vaccine.Of 193 respondents, 57.5% (n = 111) reported COVID-19 vaccine acceptance. Among those who did not accept the vaccine, concern over vaccine safety was the most commonly cited reason (90.1%, n = 73), and 81.7% (n = 67) disagreed with receiving a vaccine that had not been tested in pregnant people. Confidence in COVID-19 vaccine safety (aOR 16.72, 95% CI: 7.22, 42.39), Indigenous self-identification (aOR 11.59, 95% CI: 1.77, 117.18), and employment in an occupation at high risk for COVID-19 exposure excluding healthcare (aOR 4.76, 95% CI: 1.32, 18.60) were associated with vaccine acceptance. Perceived personal risk of COVID-19 disease was not associated with vaccine acceptance in the multivariate model.Vaccine safety is a primary concern for this population. Safety information should be communicated to this population as it emerges, along with clear messaging on the benefits of vaccination, as disease risk is either poorly understood or poorly valued in this population.RéSUMé: OBJECTIF: Examiner l’intention de se faire vacciner contre la COVID-19 et l’adoption du vaccin anti-COVID-19 chez les personnes enceintes au Canada, et déterminer les facteurs associés. MéTHODE: Du 28 mai au 7 juin 2021, nous avons mené un sondage transversal national auprès de personnes enceintes (n = 193). Les répondantes ont rempli un questionnaire pour nous permettre de déterminer l’acceptation du vaccin contre la COVID-19 (définie comme le fait d’avoir reçu ou l’intention de recevoir un vaccin anti-COVID-19 durant la grossesse), les facteurs associés à l’acceptation du vaccin et les motifs d’acceptation ou de refus du vaccin. RéSULTATS: Sur les 193 répondantes, 57,5 % (n = 111) ont dit accepter le vaccin contre la COVID-19. Chez celles qui n’acceptaient pas le vaccin, l’inquiétude face à son innocuité était la raison la plus souvent citée (90,1 %, n = 73), et 81,7 % (n = 67) n’acceptaient pas de recevoir un vaccin qui n’avait pas été testé sur des personnes enceintes. La confiance en l’innocuité du vaccin anti-COVID-19 (RCa 16,72, IC de 95 % : 7,22, 42,39), l’auto-identification en tant que personne autochtone (RCa 11,59, IC de 95 % : 1,77, 117,18) et l’emploi dans une profession à risque élevé d’exposition à la COVID-19, sauf les soins de santé (RCa 4,76, IC de 95 % : 1,32, 18,60) étaient associés à l’acceptation du vaccin. Le risque personnel perçu de tomber malade de la COVID-19 n’était pas associé à l’acceptation du vaccin dans notre modèle multivarié. CONCLUSION: L’innocuité du vaccin est une préoccupation majeure dans cette population. Des informations sur l’innocuité devraient être communiquées aux personnes enceintes au fur et à mesure qu’elles sont connues, ainsi que des messages clairs sur les avantages de la vaccination, car le risque de maladie est soit mal compris, soit déconsidéré dans cette population.

Haemophilus influenzae can cause serious invasive disease. We report the epidemiology and antimicrobial susceptibility of invasive H. influenzae in Ontario, Canada, from 2014 to 2018 from laboratory-based data. Blood was the most common specimen source (89.5%). Consistent with widespread vaccination against serotype b (Hib), the incidence of Hib in Ontario remained low (0.04 cases per 100,000 population). H. influenzae disease primarily afflicted those

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).

Background Invasive pneumococcal disease (IPD) burden, evaluated in Canada using reported confirmed cases in surveillance systems, is likely underestimated due to underreporting. We estimated the burden of IPD in Ontario and British Columbia (BC) by combining surveillance data with health administrative databases. Methods We established a cohort of 27,525 individuals in Ontario and BC. Laboratory-confirmed IPD cases were identified from Ontario’s integrated Public Health Information System and the BC Centre for Disease Control Public Health Laboratory. Possible IPD cases were identified from hospitalization data in both provinces, and from emergency department visit data in Ontario. We estimated the age and sex adjusted annual incidence of IPD and pneumococcal conjugate/polysaccharide vaccine (PCV/PPV) serotype-specific IPD using Poisson regression models. Results In Ontario, 20,205 overall IPD cases, including 15,299 laboratory-confirmed cases, were identified with relatively stable age- and sex-adjusted annual incidence rates ranging from 13.7/100,000 (2005) to 13.6/100,000 (2018). In BC, 7,320 overall IPD cases, including 5,932 laboratory-confirmed cases were identified; annual incidence rates increased from 10.9/100,000 (2002) to 13.2/100,000 (2018). Older adults aged ≥ 85 years had the highest incidence rates. During 2007–2018 the incidence of PCV7 serotypes and additional PCV13 serotypes decreased while the incidence of unique PPV23 and non-vaccine serotypes increased in both provinces. Conclusions IPD continues to cause a substantial public health burden in Canada despite publicly funded pneumococcal vaccination programs, resulting in part from an increase in unique PPV23 and non-vaccine serotypes.

SARS-CoV-2 variants of concern (VOC) are more transmissible and may have the potential for increased disease severity and decreased vaccine effectiveness. We estimated the effectiveness of BNT162b2 (Pfizer-BioNTech Comirnaty), mRNA-1273 (Moderna Spikevax) and ChAdOx1 (AstraZeneca Vaxzevria) vaccines against symptomatic SARS-CoV-2 infection and COVID-19 hospitalization or death caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) VOC in Ontario, Canada, using a test-negative design study. We identified 682,071 symptomatic community-dwelling individuals who were tested for SARS-CoV-2, and 15,269 individuals with a COVID-19 hospitalization or death. Effectiveness against symptomatic infection ≥7 d after two doses was 89-92% against Alpha, 87% against Beta, 88% against Gamma, 82-89% against Beta/Gamma and 87-95% against Delta across vaccine products. The corresponding estimates ≥14 d after one dose were lower. Effectiveness estimates against hospitalization or death were similar to or higher than against symptomatic infection. Effectiveness against symptomatic infection was generally lower for older adults (≥60 years) than for younger adults (60 years) for most of the VOC-vaccine combinations. Our findings suggest that jurisdictions facing vaccine supply constraints may benefit from delaying the second dose in younger individuals to more rapidly achieve greater overall population protection; however, older adults would likely benefit most from minimizing the delay in receiving the second dose to achieve adequate protection against VOC.

In 2017 Ontario experienced the largest mumps outbreak in the province in 8 years, at a time when multiple outbreaks were occurring across North America. Of 259 reported cases, 143 occurred in Toronto, primarily among young adults. Routine genotyping of the small hydrophobic gene indicated that the outbreak was due to mumps virus genotype G. We performed a retrospective study of whole genome sequencing of 26 mumps virus isolates from early in the outbreak, using a tiling amplicon method. Results indicated that two of the cases were genetically divergent, with the remaining 24 cases belonging to two major clades and one minor clade. Phylogeographic analysis confirmed circulation of virus from each clade between Toronto and other regions in Ontario. Comparison with other genotype G strains from North America suggested that the presence of co-circulating major clades may have been due to separate importation events from outbreaks in the United States. A transmission network analysis performed with the software program TransPhylo was compared with previously collected epidemiological data. The transmission tree correlated with known epidemiological links between nine patients and identified new potential clusters with no known epidemiological links.

Canada eliminated measles in 1998. We conducted a sero-epidemiology study to estimate population immunity to measles in the province of Ontario, Canada and to identify groups at higher risk of outbreaks. We used a previously developed modified enzyme immunoassay to test 1,199 residual sera from patients aged 1–39 years. We re-tested negative and equivocal sera using a plaque reduction neutralization assay. We interpreted our results in the context of Ontario’s immunization program and vaccine coverage data. Of 1,199 sera, 1035 (86.3%, 95% confidence interval (CI) 84.4, 88.2) were above the measles threshold for protection, 70 (5.8%, 95% CI 4.5, 7.2) were equivocal and 94 (7.8%, 95% CI 6.3, 9.4) were negative. The proportion of positive sera was highest for those 1–5 years, with 180/199 (90.5%, 95% CI 86.4, 94.5) positive sera, and lowest for those age 12–19 years, at 158/199 (79.4%, 95% CI 73.8, 85.0). Adjusted for age, females were more likely than males to have antibody titers above the threshold of protection (odds ratio = 1.60, 95% CI 1.14, 2.24). Most of the study cohort were eligible for two measles vaccine doses, and vaccine uptake in Ontario is >90% for school-aged cohorts. We observed a higher than expected proportion of sera with antibody levels below the threshold of protection, suggesting that immunity in some Ontario age-groups may be waning, despite high vaccine coverage. Alternatively, the traditional measles correlates of protection may not be an appropriate measure of population protection in measles-eliminated settings.

ObjectiveTo assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy.DesignPopulation based retrospective cohort study.SettingOntario, Canada, 1 May to 31 December 2021.ParticipantsAll liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g.Main outcome measuresUsing Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (ResultsAmong 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy—42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinatedv6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7%v4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59%v0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1%v9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25%v0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy.ConclusionThe findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth.

ObjectivesTo estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA covid-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the omicron variant.DesignTest negative design.SettingLong term care facilities in Ontario, Canada, 30 December 2021 to 27 April 2022.ParticipantsAfter exclusions, 61 344 residents aged 60 years or older across 626 long term care facilities in Ontario, Canada who were tested for SARS-CoV-2 were included.Main outcome measuresLaboratory confirmed omicron SARS-CoV-2 infection (any and symptomatic) by reverse transcription polymerase chain reaction (RT-PCR), and hospital admission or death. Multivariable logistic regression was used to estimate marginal effectiveness (four versus three doses) and vaccine effectiveness (two, three, or four doses versus no doses) while adjusting for personal characteristics, comorbidities, week of test, and previous positive SARS-CoV-2 test result more than 90 days previously.Results13 654 residents who tested positive for omicron SARS-CoV-2 infection and 205 862 test negative controls were included. The marginal effectiveness of a fourth dose (95% of vaccine recipients received mRNA-1273 as the fourth dose) seven days or more after vaccination versus a third dose received 84 or more days previously was 19% (95% confidence interval 12% to 26%) against infection, 31% (20% to 41%) against symptomatic infection, and 40% (24% to 52%) against severe outcomes. Vaccine effectiveness in vaccine recipients (compared with unvaccinated) increased with each additional dose, and for a fourth dose was 49% (95% confidence interval 43% to 54%) against infection, 69% (61% to 76%) against symptomatic infection, and 86% (81% to 90%) against severe outcomes.ConclusionsThe findings suggest that compared with a third dose of mRNA covid-19 vaccine, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes among long term care residents during an omicron dominant period. A fourth vaccine dose was associated with strong protection against severe outcomes in vaccinated residents compared with unvaccinated residents, although the duration of protection remains unknown.