Search

Background A major goal of coronavirus disease 2019 (COVID-19) vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of messenger RNA (mRNA) and ChAdOx1 COVID-19 vaccines against severe outcomes in 4 Canadian provinces between December 2020 and September 2021. Methods We conducted this multiprovincial, retrospective, test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random-effects models. Results We included 2 508 296 tested participants, with 31 776 COVID-19 hospitalizations and 5842 deaths. Vaccine effectiveness was 83% after a first dose and 98% after a second dose against both hospitalization and death (separately). Against severe outcomes, effectiveness was 87% (95% confidence interval [CI], 71%–94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95% CI, 96%–99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95% CI, 75%–94%) ≥56 days after a first dose, increasing to 97% (95% CI, 91%–99%) ≥56 days after a second dose. Lower 1-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules and against Alpha, Gamma, and Delta variants. Conclusions Two doses of mRNA or ChAdOx1 vaccine provide excellent protection against severe outcomes.

Background Increased immune evasion by emerging SARS-CoV-2 variants and occurrence of breakthrough infections raise questions about whether COVID-19 vaccination status impacts SARS-CoV-2 viral load among those infected. This study examined the relationship between cycle threshold (Ct) value, which is inversely associated with viral load, and vaccination status at the Omicron wave onset in Ontario, Canada. Methods Using linked provincial databases, we compared median Ct values across vaccination status among PCR-confirmed Omicron variant SARS-CoV-2 cases (sub-lineages B.1.1.529, BA.1 and BA.1.1) between December 6 and 30, 2021. Cases were presumed to be Omicron based on S-gene target failure (SGTF). We estimated the relationship between vaccination status and Ct values using multiple linear regression, adjusting for age group, sex and symptom status. Results Of the 27,029 presumed Omicron cases in Ontario, the majority were among post-vaccination series completed cases (87.7%), followed by unvaccinated (8.1%), and post-booster dose cases (4.2%). Median Ct value for post-booster dose (18.3, Interquartile range (IQR): 15.4-22.3) was significantly higher than that for unvaccinated (17.9, IQR: 15.2-21.6, p = 0.018) and post-series completion cases (17.8, IQR: 15.3-21.5, p = 0.005). Post-booster dose cases remained associated with a significantly higher median Ct value than unvaccinated cases (p= Conclusions While slightly lower Ct values were observed among unvaccinated individuals infected with Omicron compared to post-booster dose cases, further research is required to determine if a significant difference in secondary transmission exists between these groups.

Respiratory syncytial virus (RSV) is a major cause of acute respiratory infection (ARI), with high morbidity and mortality worldwide. RSV costing and burden estimates can highlight the potential benefits of future vaccination programs and are essential for economic evaluations.We aimed to determine RSV healthcare costs across age groups and the overall disease burden of medically attended RSV in Canada.We conducted a retrospective case-control study to estimate the attributable healthcare costs per RSV case in Alberta. We used two case definitions to capture diversity in case severity: laboratory-confirmed RSV and ARI attributable to RSV. Matching occurred on five criteria: (1) age, (2) urban/rural status, (3) sex, (4) prematurity and (5) Charlson Comorbidity Index score. We calculated the age-specific burden of medically attended RSV in Canada from 2010 to 2019 by multiplying the weekly age-specific incidence of medically attended ARI with the RSV positivity rate.Costs per laboratory-confirmed RSV case were (in Canadian dollars [CAD], year 2020 values) $CAD12,713 and 40,028 in the first 30 and 365 days following diagnosis, respectively, whereas a case of ARI potentially attributable to RSV cost $CAD316 and 915, in 30 and 365 days, respectively. Older (aged ≥ 65 years) and younger (aged 90 days) age groups had the highest case costs. The average medically attended RSV incidence rate across nine seasons was 1743 cases per 100,000 people per year.RSV is a common and expensive infection at the extremes of life, and the development of immunization programs targeting older and younger ages may be important for the reduction of RSV burden and cost.

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.

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.

COG-UK is supported by funding from the MRC part of UK Research & Innovation, the National Institute of Health Research (Grant code MC_PC_19027), and Genome Research Limited, operating as the Welcome Sanger Institute. Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine. Publisher PDF

List of genes represented in the heatmap

Purpose: PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DC). DC signals can be bypassed by CD27 agonists, and we therefore investigated if the effectiveness of anti–PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb).Experimental Design: The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models. Global transcriptional profiling and flow cytometry analysis were used to delineate mechanisms underpinning the observed synergy.Results: PD-1/PD-L1 blockade and agonist anti-CD27 mAb synergize for increased CD8+ T-cell expansion and effector function, exemplified by enhanced IFNγ, TNFα, granzyme B, and T-bet. Transcriptome analysis of CD8+ T cells revealed that combination therapy triggered a convergent program largely driven by IL2 and Myc. However, division of labor was also apparent such that anti–PD-1/L1 activates a cytotoxicity–gene expression program whereas anti-CD27 preferentially augments proliferation. In tumor models, either dependent on endogenous CD8+ T cells or adoptive transfer of transgenic T cells, anti-CD27 mAb synergized with PD-1/L1 blockade for antitumor immunity. Finally, we show that a clinically relevant anti-human CD27 mAb, varlilumab, similarly synergizes with PD-L1 blockade for protection against lymphoma in human–CD27 transgenic mice.Conclusions: Our findings suggest that suboptimal T-cell invigoration in cancer patients undergoing treatment with PD-1 checkpoint blockers will be improved by dual PD-1 blockade and CD27 agonism and provide mechanistic insight into how these approaches cooperate for CD8+ T-cell activation. Clin Cancer Res; 24(10); 2383–94. ©2018 AACR.

Figure S1: Agonist anti-CD27 is superior to other anti-TNFRSF mAbs for CD8+ T-cell expansion in vivo; Figure S2: Agonist anti-CD27 and PD-1/L1 blockade combine to promote expansion of OT-I T cells in response to high and low affinity peptides; Figure S3: Purity of pmel1 CD8+ T cells prior to microarray analysis; Figure S4: Agonist anti-CD27 and PD-1 blockade synergize for improved adoptive T-cell therapy; Figure S5: Agonist anti-CD27 and anti-PD-L1 synergize to impair tumor growth and improve local CD8+ T-cell accumulation in a vaccination model.

Background Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk. Methods Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010–2011 to 2018–2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status. Results Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%–20%] and 17% [13%–21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10–1.21] and 1.15 [1.10–1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for β-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated β-blocker users. Conclusions Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding.

BackgroundTo inform planning for further booster doses of COVID-19 vaccines, we estimated the effectiveness of monovalent mRNA vaccines against Omicron-associated severe outcomes in adults over time.MethodsWe used a test-negative design and multivariable logistic regression to estimate vaccine effectiveness (VE; 2, 3, or 4 doses compared to unvaccinated individuals) and marginal effectiveness (3 or 4 doses compared to 2 doses) against Omicron-associated hospitalization or death among community-dwelling adults aged ≥50 years who were tested for SARS-CoV-2 between January 2, 2022 and October 1, 2022 in Ontario, Canada, stratified by age group and time since vaccination. We also compared VE during periods of Omicron BA.1/BA.2 and BA.4/BA.5 sublineage predominance.ResultsWe included 11,160 cases of Omicron-associated severe outcomes and 62,880 test-negative symptomatic controls. Depending on the age group, compared to unvaccinated individuals, 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. Trends in marginal effectiveness were consistent with VE estimates. VE was lower during the BA.4/BA.5-predominant period compared to the BA.1/BA.2-predominant period based on the same intervals since vaccination.ConclusionOur findings suggest that 1 or 2 booster doses of monovalent mRNA COVID-19 vaccines initially restored very strong protection against Omicron-associated severe outcomes in all age groups, but VE subsequently declined over time with some age-related differences, and particularly so during a period of BA.4/BA.5 predominance.

BACKGROUND With the growing volume and complexity of laboratory repositories, it has become tedious to parse unstructured data into structured and tabulated formats for secondary uses such as decision support, quality assurance, and outcome analysis. However, advances in Natural Language Processing (NLP) approaches have enabled efficient and automated extraction of clinically meaningful medical concepts from unstructured reports. OBJECTIVE In this study, we aim to determine the feasibility of using the NLP model for information extraction as an alternative approach to a time-consuming and operationally resource-intensive handcrafted rule-based tool. Therefore, we seek to develop and evaluate a deep learning-based NLP model to derive knowledge and extract information from text-based laboratory reports sourced from a provincial laboratory repository system. METHODS The NLP model, a hierarchical multi-label classifier, is trained on a corpus of laboratory reports covering testing for 14 different respiratory viruses and viral subtypes. The corpus includes 85k unique laboratory reports annotated by eight Subject Matter Experts (SME). The classification task involves assigning the laboratory reports to labels at two levels: 24 fine-grained labels in level 1 and 6 coarse-grained labels in level 2. A “label” also refers to a status of a specific virus or strain being tested or Detected (e.g., influenza A is detected). The model’s performance stability and variation were analyzed across all labels in the classification task. Moreover, the model's generalizability was also evaluated internally and externally on various test sets. RESULTS Overall, the NLP model performed well on internal, out-of-time (pre-COVID-19), and external (different laboratories) test sets with micro-averaged F1 scores >94% across all classes. Higher Precision and Recall scores with less variability were observed for the internal and pre-COVID-19 test sets. As expected, the model's performance varied across categories and virus types due to the imbalanced nature of the corpus and sample sizes per class. There were intrinsically fewer classes of viruses being detected than those tested; therefore, the model's performance (lowest F1-score of 57%) was noticeably lower in the detected cases. CONCLUSIONS We demonstrated that deep learning-based NLP models are promising solutions for information extraction from text-based laboratory reports. These approaches enable scalable, timely, and practical access to high-quality and encoded laboratory data if integrated into laboratory information system repositories CLINICALTRIAL

BackgroundWith the growing volume and complexity of laboratory repositories, it has become tedious to parse unstructured data into structured and tabulated formats for secondary uses such as decision support, quality assurance, and outcome analysis. However, advances in Natural Language Processing (NLP) approaches have enabled efficient and automated extraction of clinically meaningful medical concepts from unstructured reports.ObjectiveIn this study, we aimed to determine the feasibility of using the NLP model for information extraction as an alternative approach to a time-consuming and operationally resource-intensive handcrafted rule-based tool. Therefore, we sought to develop and evaluate a deep learning-based NLP model to derive knowledge and extract information from text-based laboratory reports sourced from a provincial laboratory repository system.MethodsThe NLP model, a hierarchical multi-label classifier, was trained on a corpus of laboratory reports covering testing for 14 different respiratory viruses and viral subtypes. The corpus included 85kunique laboratory reports annotated by eight Subject Matter Experts (SME). The model’s performance stability and variation were analyzed across fine-grained and coarse-grained classes. Moreover, the model’s generalizability was also evaluated internally and externally on various test sets.ResultsThe NLP model was trained several times with random initialization on the development corpus, and the results of the top ten best-performing models are presented in this paper. Overall, the NLP model performed well on internal, out-of-time (pre-COVID-19), and external (different laboratories) test sets with micro-averaged F1 scores >94% across all classes. Higher Precision and Recall scores with less variability were observed for the internal and pre-COVID-19 test sets. As expected, the model’s performance varied across categories and virus types due to the imbalanced nature of the corpus and sample sizes per class. There were intrinsically fewer classes of viruses beingdetectedthan thosetested; therefore, the model’s performance (lowest F1-score of 57%) was noticeably lower in the “detected” cases.ConclusionsWe demonstrated that deep learning-based NLP models are promising solutions for information extraction from text-based laboratory reports. These approaches enable scalable, timely, and practical access to high-quality and encoded laboratory data if integrated into laboratory information system repositories.

Background Nursing home (NH) residents are prioritized for COVID-19 vaccination. We report monthly mortality, hospitalizations, and emergency department (ED) visit incidence rates (IRs) during 2010–2020 to provide context for COVID-19 vaccine safety assessments. Methods We observed outcomes among all NH residents in Ontario using administrative databases. IRs were calculated by month, sex, and age group. Comparisons between months were assessed using one-sample t-tests; comparisons by age and sex were assessed using chi-squared tests. Results From 2010 to 2019, there were 83,453 (SD: 652.4) NH residents per month, with an average of 2.3 (SD: 0.28) deaths, 3.1 (SD: 0.16) hospitalizations, and 3.6 (SD: 0.17) ED visits per 100 residents per month. From March to December 2020, mortality IRs were increased, but hospitalization and ED visit IRs were reduced (p Conclusion We identified consistent monthly mortality, hospitalization, and ED visit IRs during 2010–2019. Marked differences in these rates were observed during 2020, coinciding with the COVID-19 pandemic.

People with HIV were underrepresented in coronavirus disease 2019 (COVID-19) vaccine clinical trials. We estimated vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for the BNT162b2, mRNA-1273, and ChAdOx1 vaccines among a population-based cohort of people with HIV in Ontario, Canada.Test-negative design.We identified people with HIV aged ≥19 years who were tested for SARS-CoV-2 by RT-PCR between December 14, 2020 (first availability of COVID-19 vaccines) and November 21, 2021 (pre-Omicron circulation). Outcomes included any infection, symptomatic infection, and COVID-19-related hospitalization/death. We compared the odds of vaccination between test-positive cases and test-negative controls using multivariable logistic regression with adjustment for age, sex, region, calendar time, SARS-CoV-2 test histories, influenza vaccination, comorbidities, and neighborhood-level socio-economic status. VE was derived as (1 - adjusted odds ratio) × 100%.Among 21 023 adults living with HIV, there were 801 (8.3%) test-positive cases and 8,879 (91.7%) test-negative controls. 20.1% cases and 47.8% of controls received ≥1 COVID-19 vaccine dose; among two-dose recipients, 93.4% received ≥1 mRNA dose. Two-dose VE ≥7 days before specimen collection was 82% (95% confidence interval [CI] = 74-87%) against any infection, 94% (95% CI = 82-98%) against symptomatic infection, and 97% (95% CI = 85-100%) against hospitalization/death. Against any infection, VE declined from 86% (95% CI = 77-92%) within 7-59 days after the second dose to 66% (95% CI = -15-90%) after ≥180 days; we did not observe evidence of waning protection for other outcomes.Two doses of COVID-19 vaccine offered substantial protection against symptomatic illness and hospitalization/death in people with HIV prior to the emergence of the Omicron variant. Our findings do not support a broad conclusion that COVID-19 VE is lower among people with HIV in populations that, for the most part, are attending HIV care, taking antiretroviral medication, and are virally suppressed.

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.

RESUME CONTEXTE: Les interventions non pharmacologiques demeurent le principal moyen de maitriser le coronavirus du syndrome respiratoire aigu severe 2 (SRAS-CoV-2) d’ici a ce que la couverture vaccinale soit suffisante pour donner lieu a une immunite collective. Nous avons utilise des donnees de mobilite anonymisees de telephones intelligents afin de quantifier le niveau de mobilite requis pour maitriser le SRAS-CoV-2 (c.-a-d., seuil de mobilite), et la difference par rapport au niveau de mobilite observe (c.-a-d., ecart de mobilite). METHODES: Nous avons procede a une analyse de series chronologiques sur l’incidence hebdomadaire du SRAS-CoV-2 au Canada entre le 15 mars 2020 et le 6 mars 2021. Le parametre mesure etait le taux de croissance hebdomadaire, defini comme le rapport entre les cas d’une semaine donnee et ceux de la semaine precedente. Nous avons mesure les effets du temps moyen passe hors domicile au cours des 3 semaines precedentes a l’aide d’un modele de regression log-normal, en tenant compte de la province, de la semaine et de la temperature moyenne. Nous avons calcule le seuil de mobilite et l’ecart de mobilite pour le SRAS-CoV-2. RESULTATS: Au cours des 51 semaines de l’etude, en tout, 888 751 personnes ont contracte le SRAS-CoV-2. Chaque augmentation de 10 % de l’ecart de mobilite a ete associee a une augmentation de 25 % du taux de croissance des cas hebdomadaires de SRAS-CoV-2 (rapport 1,25, intervalle de confiance a 95 % 1,20–1,29). Comparativement a la mobilite prepandemique de reference de 100 %, le seuil de mobilite a ete plus eleve au cours de l’ete (69 %, ecart interquartile [EI] 67 %–70 %), et a chute a 54 % pendant l’hiver 2021 (EI 52 %–55 %); un ecart de mobilite a ete observe au Canada entre juillet 2020 et la derniere semaine de decembre 2020. INTERPRETATION: La mobilite permet de predire avec fiabilite et constance la croissance des cas hebdomadaires et il faut maintenir des niveaux faibles de mobilite pour maitriser le SRAS-CoV-2 jusqu’a la fin du printemps 2021. Les donnees de mobilite anonymisees des telephones intelligents peuvent servir a guider le relâchement ou le resserrement des mesures de distanciation physique provinciales et regionales.

BACKGROUND: Nonpharmaceutical interventions remain the primary means of controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) until vaccination coverage is sufficient to achieve herd immunity. We used anonymized smartphone mobility measures to quantify the mobility level needed to control SARS-CoV-2 (i.e., mobility threshold), and the difference relative to the observed mobility level (i.e., mobility gap). METHODS: We conducted a time-series study of the weekly incidence of SARS-CoV-2 in Canada from Mar. 15, 2020, to Mar. 6, 2021. The outcome was weekly growth rate, defined as the ratio of cases in a given week versus the previous week. We evaluated the effects of average time spent outside the home in the previous 3 weeks using a log-normal regression model, accounting for province, week and mean temperature. We calculated the SARS-CoV-2 mobility threshold and gap. RESULTS: Across the 51-week study period, a total of 888 751 people were infected with SARS-CoV-2. Each 10% increase in the mobility gap was associated with a 25% increase in the SARS-CoV-2 weekly case growth rate (ratio 1.25, 95% confidence interval 1.20–1.29). Compared to the prepandemic baseline mobility of 100%, the mobility threshold was highest in the summer (69%; interquartile range [IQR] 67%–70%), and dropped to 54% in winter 2021 (IQR 52%–55%); a mobility gap was present in Canada from July 2020 until the last week of December 2020. INTERPRETATION: Mobility strongly and consistently predicts weekly case growth, and low levels of mobility are needed to control SARS-CoV-2 through spring 2021. Mobility measures from anonymized smartphone data can be used to guide provincial and regional loosening and tightening of physical distancing measures.

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.

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.

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.

BackgroundA major goal of COVID-19 vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against severe outcomes in four Canadian provinces between December 2020 and September 2021.MethodsWe conducted this multiprovincial retrospective test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random effects models.ResultsWe included 2,508,296 tested subjects, with 31,776 COVID-19 hospitalizations and 5,842 deaths. Vaccine effectiveness was 83% after a first dose, and 98% after a second dose, against both hospitalization and death (separately). Against severe outcomes (hospitalization or death), effectiveness was 87% (95%CI: 71%–94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95%CI: 96%–99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95%CI: 75%–94%) ≥56 days after a first dose, increasing to 97% (95%CI: 91%–99%) ≥56 days after a second dose. Lower one-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules, and against Alpha, Gamma, and Delta variants.ConclusionsTwo doses of mRNA or ChAdOx1 vaccines provide excellent protection against severe outcomes of hospitalization and death.

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.

Background For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventive and/or therapeutic activity. Epidemiologic studies could complement laboratory-focused efforts to identify possible therapeutic agents. Methods We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older individuals (≥65 years) in long-term care homes (LTCHs) and the community, between 15 January 2020 and 31 December 2020, across the province of Ontario, Canada. Results A total of 26 121 cases and 2 369 020 controls from LTCHs and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared to be significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted odds ratio [OR], 0.91; standard P Conclusions Using this epidemiologic approach, which can be applied to current and future pandemics, we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in coronavirus disease 2019 (COVID-19) and may warrant further validation. Some of these agents (eg, fluoxetine) have already been identified for their therapeutic potential.

Background: Vaccines against SARS-CoV-2 have been shown to reduce risk of infection, as well as severe disease among those with breakthrough infection, in adults. The latter effect is particularly important as Immune evasion by Omicron variants appears to have made vaccines less effective for prevention of infection. There is currently little available information on the protection conferred by vaccination against severe illness due to SARS-CoV-2 in children. Methods: To minimize confounding by changing vaccination practices and dominant circulating viral variants, we performed an age- and time-matched nested case-control design. Reported SARS-CoV-2 case records in Ontario children and adolescents aged 4 to 17 were linked to vaccination records. We used multivariable logistic regression to estimate the effectiveness of one and two vaccine doses against hospitalization. Results: We identified 130 hospitalized SARS-CoV-2 cases and 1,300 non-hospitalized, age- and time-matched controls, with disease onset between May 28, 2021 and January 9, 2022. One vaccine dose was shown to be 34% effective against hospitalization among SARS-CoV-2 cases (aOR = 0.66 [95% CI: 0.34, 1.21]). In contrast, two doses were 56% (aOR = 0.44 [95% CI: 0.23, 0.83]) effective at preventing hospitalization among SARS-CoV-2 cases. Exploratory instrumental variable analyses, and calculation of E-values, suggested that these effects are unlikely to be explained by unmeasured confounding. Conclusions: Even with immune evasion by SARS-CoV-2 variants, two vaccine doses continue to provide protection against hospitalization among adolescent and pediatric SARS-CoV-2 cases, even when the vaccines do not prevent infection.

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 (

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.

As of January 22, 2020, "disease caused by a novel coronavirus" became a reportable disease of public health significance in Ontario. Public health units were provided with guidance on the entry of patients tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing 2019 coronavirus disease (COVID-19), into the provincial public health information system. Between January 22 and February 22, 2020, there were 359 individuals who had a negative test result recorded and three confirmed cases of COVID-19. Of those who tested negative, 51% were female and 71% were under 50 years of age. The most common symptoms reported were cough (55%), fever (37%) and sore throat (35%). The majority were tested within three days of symptom onset, but over one-quarter tested more than seven days after symptom onset. Over the first month of reportability, reported travel history shifted from China to an increasing proportion with travel outside of China.