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AbstractObjectiveTo estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death).DesignTest negative design study.SettingOntario, Canada between 14 December 2020 and 19 April 2021.Participants324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2.InterventionsBNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine.Main outcome measuresLaboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes.ResultsOf 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation.ConclusionsTwo doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

Tuberculosis is one of the leading causes of death worldwide. Twenty-two high burden countries contributed to the majority of worldwide tuberculosis cases in 2015. Health care workers are at high risk of acquiring tuberculosis through occupational exposure. To estimate the prevalence of latent tuberculosis infection (LTBI) among health care workers in high burden countries. Databases including MEDLINE (Ovid), EMBASE (Ovid), CINAHL (Ovid) and ISI Web of Science (Thompson-Reuters), and grey literature were searched for English language records on relevant medical subject headings (MeSH) terms of LTBI and health care providers. Literature was systematically reviewed using EPPI-Reviewer4 software. Prevalence and incidence of LTBI and 95% confidence intervals (CI) were reported. Pooled prevalence of LTBI and 95% CI were calculated using random-effects meta-analysis models and heterogeneity was assessed using I2 statistics. Sub-group analysis was conducted to assess the cause of heterogeneity. A total of 990 records were identified. Of those, 18 studies from only 7 high burden countries representing 10,078 subjects were included. Tuberculin skin test results were available for 9,545 participants. The pooled prevalence of LTBI was 47% (95% CI 34% to 60%, I2 = 99.6%). In subgroup analyses according to the country of the study, the pooled prevalence of LTBI was lowest in Brazil (37%) and highest in South Africa (64%). The pooled prevalence of LTBI among medical and nursing students was 26% (95% CI 6% to 46%, I2 = 99.3%) while the prevalence among all types of health care workers was 57% (95% CI 44% to 70%, I2 = 99.1%). Incidence of LTBI was available for health care workers in four countries. The cumulative incidence ranged from 2.8% in Brazilian medical students to 38% among all types of health care workers in South Africa. The findings of this study suggest that there is a high burden of LTBI among health care workers in high burden countries. Adequate infection control measures are warranted to prevent and control transmission in health care settings.

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. Analysis of the effectiveness of three vaccines to protect against symptomatic SARS-CoV-2 infection and severe outcomes caused by Alpha, Beta, Gamma and Delta variants in Ontario, Canada, suggests that a single dose provides considerable protection, two doses provide even higher protection, and effectiveness against hospitalization or death is similar to or higher than against symptomatic infection.

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.

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

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. This study investigates the protection provided by mRNA COVID-19 vaccine booster doses against Omicron-associated severe disease in adults aged 50 and older. The authors use data from Ontario, Canada, and find that booster doses provide strong protection but that it declined during the period of BA.4/BA.5 predominance.

Background. Although influenza is a vaccine-preventable disease that annually causes substantial disease burden, data on virus activity in tropical countries are limited. We analyzed publicly available influenza data to better understand the global circulation of influenza viruses. Method. We reviewed open-source, laboratory-confirmed influenza surveillance data. For each country, we abstracted data on the percentage of samples testing positive for influenza each epidemiologic week from the annual number of samples testing positive for influenza. The start of influenza season was defined as the first week when the proportion of samples that tested positive remained above the annual mean. We assessed the relationship between percentage of samples testing positive and mean monthly temperature with use of regression models. Findings. We identified data on laboratory-confirmed influenza virus infection from 85 countries. More than one influenza epidemic period per year was more common in tropical countries (41%) than in temperate countries (15%). Year-round activity (ie, influenza virus identified each week having ≥10 specimens submitted) occurred in 3 (7%) of 43 temperate, 1 (17%) of 6 subtropical, and 11 (37%) of 30 tropical countries with available data (P = .006). Percentage positivity was associated with low temperature (P = .001). Interpretation. Annual influenza epidemics occur in consistent temporal patterns depending on climate.

Background There is low uptake of the pneumococcal vaccination in eligible older adults, even in high-income countries that offer routine and universal vaccination programs. Objective To systematically characterize interventions aimed at improving pneumococcal vaccine uptake in older adults. Design We conducted a scoping review following PRISMA-SCr guidelines of five interdisciplinary databases: Medline-Ovid, Embase, CINAHL, PsychInfo, and Cochrane Library. Databases were searched from January 2015 until April 2020. The interventions were summarized into three pillars according to the European Union Conceptional Framework for Action: information campaigns, prioritization of vaccination schemes, and primary care interventions. Results Our scoping review included 39 studies that summarized interventions related to pneumococcal vaccine uptake for older adults, encompassing 2,481,887 study participants (945 healthcare providers and 2,480,942 older adults) across seven countries. Examples of interventions that were associated with increased pneumococcal vaccination rate included periodic health examinations, reminders and decision-making tools built into electronic medical records, inpatient vaccination protocols, preventative health checklists, and multimodal educational interventions. When comparing the three pillars, prioiritization of vaccination schemes had the highest evidence for improved rates of vaccination ( n  = 14 studies), followed by primary care interventions ( n  = 8 studies), then information campaigns ( n  = 5 studies). Conclusion Several promising interventions were associated with improved outcomes related to vaccine uptake, although controlled study designs are needed to determine which interventions are most effective.

BackgroundEarly evidence on COVID-19 vaccine efficacy came from randomised trials. Many important questions subsequently about vaccine effectiveness (VE) have been addressed using real-world studies (RWS) and have informed most vaccination policies globally. As the questions about VE have evolved during the pandemic so have data, study design, and analytical choices. This scoping review aims to characterise this evolution and provide insights for future pandemic planning—specifically, what kinds of questions are asked at different stages of a pandemic, and what data infrastructure and methods are used?Methods and analysisWe will identify relevant studies in the Johns Hopkins Bloomberg School of Public Health VIEW-hub database, which curates both published and preprint VE RWS identified from PubMed, Embase, Scopus, Web of Science, the WHO COVID Database, MMWR, Eurosurveillance, medRxiv, bioRxiv, SSRN, Europe PMC, Research Square, Knowledge Hub, and Google. We will include RWS of COVID-19 VE that reported COVID-19-specific or all-cause mortality (coded as ‘death’ in the ‘effectiveness studies’ data set).Information on study characteristics; study context; data sources; design and analytic methods that address confounding will be extracted by single reviewer and checked for accuracy and discussed in a small group setting by methodological and analytic experts. A timeline mapping approach will be used to capture the evolution of this body of literature.By describing the evolution of RWS of VE through the COVID-19 pandemic, we will help identify options for VE studies and inform policy makers on the minimal data and analytic infrastructure needed to support rapid RWS of VE in future pandemics and of healthcare strategies more broadly.Ethics and disseminationAs data is in the public domain, ethical approval is not required. Findings of this study will be disseminated through peer-reviewed publications, conference presentations, and working-papers to policy makers.Registrationhttps://doi.org/10.17605/OSF.IO/ZHDKR