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BackgroundShared and divergent predictors of clinical severity across respiratory viruses may support clinical and community responses in the context of a novel respiratory pathogen. MethodsWe conducted a retrospective cohort study to identify predictors of 30-day all-cause mortality following hospitalization with influenza (N=45,749; 2011-09 to 2019-05), respiratory syncytial virus (RSV; N=24,345; 2011-09 to 2019-04), or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; N=8,988; 2020-03 to 2020-12; pre-vaccine) using population-based health administrative data from Ontario, Canada. Multivariable modified Poisson regression was used to assess associations between potential predictors and mortality. We compared the direction, magnitude, and confidence intervals of risk ratios to identify shared and divergent predictors of mortality. Results3,186 (7.0%), 697 (2.9%) and 1,880 (20.9%) patients died within 30 days of hospital admission with influenza, RSV, and SARS-CoV-2, respectively. Shared predictors of increased mortality included: older age, male sex, residence in a long-term care home, and chronic kidney disease. Positive associations between age and mortality were largest for patients with SARS-CoV-2. Few comorbidities were associated with mortality among patients with SARS-CoV-2 as compared to those with influenza or RSV. ConclusionsOur findings may help identify patients at greatest risk of illness secondary to a respiratory virus, anticipate hospital resource needs, and prioritize local prevention and therapeutic strategies to communities with higher prevalence of risk factors.
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ImportanceSocial determinants of health (SDOH) play an important role in COVID-19 outcomes. More research is needed to quantify this relationship and understand the underlying mechanisms. ObjectivesTo examine differential patterns in COVID-19-related mortality by area-level SDOH accounting for confounders; and to compare these patterns to those for non-COVID-19 mortality, and COVID-19 case fatality (COVID-19-related death among those diagnosed). Design, setting, and participantsPopulation-based retrospective cohort study including all community living individuals aged 20 years or older residing in Ontario, Canada, as of March 1, 2020 who were followed through to March 2, 2021. ExposureSDOH variables derived from the 2016 Canada Census at the dissemination area-level including: median household income; educational attainment; proportion of essential workers, racialized groups, recent immigrants, apartment buildings, and high-density housing; and average household size. Main outcomes and measuresCOVID-19-related death was defined as death within 30 days following, or 7 days prior to a positive SARS-CoV-2 test. Cause-specific hazard models were employed to examine the associations between SDOH and COVID-19-related mortality, treating non-COVID-19 mortality as a competing risk. ResultsOf 11,810,255 individuals included, 3,880 (0.03%) died related to COVID-19 and 88,107 (0.75%) died without a positive test. After accounting for demographics, baseline health, and other SDOH, the following SDOH were associated with increased hazard of COVID-19-related death (hazard ratios [95% confidence intervals]) comparing the most to least vulnerable group): lower income (1.30[1.09-1.54]), lower educational attainment (1.27[1.10-1.47]), higher proportion essential workers (1.28[1.10-1.50]), higher proportion racialized groups (1.42[1.16-1.73]), higher proportion apartment buildings (1.25[1.11-1.41]), and larger vs. medium household size (1.30[1.13-1.48]). In comparison, areas with higher proportion racialized groups were associated with a lower hazard of non-COVID-19 mortality (0.88[0.85-0.92]). With the exception of income, SDOH were not independently associated with COVID-19 case fatality. Conclusions and relevanceArea-level social and structural inequalities determine COVID-19-related mortality after accounting for individual demographic and clinical factors. COVID-19 has reversed the pattern of lower non-COVID-19 mortality by racialized groups. Pandemic responses should include prioritized and community-tailored intervention strategies to address SDOH that mechanistically underpin disproportionate acquisition and transmission risks and shape barriers to the reach of, and access to prevention interventions. Key pointsO_ST_ABSQuestionC_ST_ABSAre area-level social determinants of health factors independently associated with coronavirus disease 2019 (COVID-19)-related mortality after accounting for demographics and clinical factors? FindingsIn this population-based cohort study including 11.8 million adults residing in Ontario, Canada and 3,880 COVID-19-related death occurred between Mar 1, 2020 and Mar 2, 2021, we found that areas characterized by lower SES (including lower income, lower educational attainment, and higher proportion essential workers), greater ethnic diversity, more apartment buildings, and larger vs. medium household size were associated with increased hazard of COVID-19-related mortality compared to their counterparts, even after accounting for individual-level demographics, baseline health, and other area-level SDOH. MeaningPandemic responses should include prioritized and community-tailored intervention strategies to address SDOH that mechanistically underpin inequalities in acquisition and transmission risks, and in the reach of, and access to prevention interventions.
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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 Bells palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barre 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 Bells 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-Barre 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-Barre syndrome. Bells palsy, acute disseminated encephalomyelitis, and Guillain-Barre 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.
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SARS-CoV-2 variants of concern (VOC) are more transmissible and 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) VOCs in Ontario, Canada using a test-negative design study. Effectiveness against symptomatic infection [≥]7 days 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 days after one dose were lower. Effectiveness estimates against hospitalization or death were similar to, or higher than, against symptomatic infection. Effectiveness against symptomatic infection is generally lower for older adults ([≥]60 years) compared to younger adults (<60 years) for most of the VOC-vaccine combinations.
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ObjectivesTo estimate the effectiveness of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. DesignWe applied a test-negative design study to linked laboratory, vaccination, and health administrative databases, and used multivariable logistic regression adjusting for demographic and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness (VE) against symptomatic infection and severe outcomes. SettingOntario, Canada between 14 December 2020 and 19 April 2021. ParticipantsCommunity-dwelling adults aged [≥]16 years who had COVID-19 symptoms and were tested for SARS-CoV-2. InterventionsPfizer-BioNTechs BNT162b2 or Modernas mRNA-1273 vaccine. Main outcome measuresLaboratory-confirmed SARS-CoV-2 by RT-PCR; hospitalization/death associated with SARS-CoV-2 infection. ResultsAmong 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received [≥]1 vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. VE against symptomatic infection [≥]14 days after receiving only 1 dose was 60% (95%CI, 57 to 64%), increasing from 48% (95%CI, 41 to 54%) at 14-20 days after the first dose to 71% (95%CI, 63 to 78%) at 35-41 days. VE [≥]7 days after 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, VE [≥]14 days after 1 dose was 70% (95%CI, 60 to 77%), increasing from 62% (95%CI, 44 to 75%) at 14-20 days to 91% (95%CI, 73 to 97%) at [≥]35 days, whereas VE [≥]7 days after 2 doses was 98% (95%CI, 88 to 100%). For adults aged [≥]70 years, VE estimates were lower for intervals shortly after receiving 1 dose, but were comparable to younger adults for all intervals after 28 days. After 2 doses, we observed high VE against E484K-positive variants. ConclusionsTwo doses of mRNA COVID-19 vaccines are highly effective against symptomatic infection and severe outcomes. Single-dose effectiveness is lower, particularly for older adults shortly after the first dose.
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BackgroundInequities in the burden of COVID-19 observed across Canada suggest heterogeneity within community transmission. ObjectivesTo quantify the magnitude of heterogeneity in the wider community (outside of long-term care homes) in Toronto, Canada and assess how the magnitude in concentration evolved over time (January 21 to November 21, 2020). DesignRetrospective, population-based observational study using surveillance data from Ontarios Case and Contact Management system. SettingToronto, Canada. ParticipantsLaboratory-confirmed cases of COVID-19 (N=33,992). MeasurementsWe generated epidemic curves by SDOH and crude Lorenz curves by neighbourhoods to visualize inequities in the distribution of COVID-19 cases by social determinants of health (SDOH) and estimated the crude Gini coefficient. We examined the correlation between SDOH using Pearson correlation coefficients. ResultsThe Gini coefficient of cumulative cases by population size was 0.41 (95% CI: 0.36-0.47) and were estimated for: household income (0.20, 95%CI: 0.14-0.28); visible minority (0.21, 95%CI: 0.16-0.28); recent immigration (0.12, 95%CI: 0.09-0.16); suitable housing (0.21, 95%CI: 0.14-0.30); multi-generational households (0.19, 95%CI: 0.15-0.23); and essential workers (0.28, 95% CI: 0.23-0.34). Most SDOH were highly correlated. Locally acquired cases were concentrated in higher income neighbourhoods in the early phase of the epidemic, and then concentrated in lower income neighbourhoods. Mirroring the trajectory of epidemic curves by income, the Lorenz curve shifted over time from below to above the line of equality with a similar pattern across SDOH. LimitationsStudy relied on area-based measures of the SDOH and individual case counts of COVID-19. We cannot infer concentration of cases by specific occupational exposures given limitation to broad occupational categories. ConclusionCOVID-19 is increasingly concentrated by SDOH given socioeconomic inequities and structural racism. Primary Funding SourceCanadian Institutes of Health Research.
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ObjectiveThe objective of this study was to estimate background rates of selected thromboembolic and coagulation disorders in Ontario, Canada. DesignPopulation-based retrospective observational study using linked health administrative databases. Records of hospitalizations and emergency department visits were searched to identify cases using diagnostic codes from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Canada (ICD-10-CA). ParticipantsAll Ontario residents. Primary outcome measuresIncidence rates of stroke, deep vein thrombosis, pulmonary embolism, idiopathic thrombocytopenia, disseminated intravascular coagulation, and cerebral venous thrombosis during five pre-pandemic years (2015-2019, annually, averaged, and monthly average) and 2020. ResultsThe average annual population was 14 million with 51% female. The mean annual rates during 2015-2019 were 127.1/100,000 population (95% confidence interval [CI], 126.2, 127.9) for ischemic stroke, 22.0/100,000 (95%CI, 21.6, 22.3) for intracerebral haemorrhage, 9.4 (95%CI, 9.2, 9.7) for subarachnoid haemorrhage, 86.8/100,000 (95%CI, 86.1, 87.5) for deep vein thrombosis, 63.7/100,000 (95%CI, 63.1, 64.3) for pulmonary embolism, 6.1/100,000 (95%CI, 5.9, 6.3) for idiopathic thrombocytopenia, 1.6/100,000 (95%CI, 1.5, 1.7) for disseminated intravascular coagulation, and 1.5/100,000 (95%CI, 1.4, 1.6) for cerebral venous thrombosis. Rates were lower in 2020 than during the pre-pandemic years for ischemic stroke, deep vein thrombosis, and idiopathic thrombocytopenia. Rates were generally consistent over time, except for pulmonary embolism, which increased from 57.1 to 68.5 per 100,000 between 2015 and 2019. Rates were higher for females than males for subarachnoid haemorrhage, pulmonary embolism, and cerebral venous thrombosis, and vice versa for ischemic stroke and intracerebral haemorrhage. Rates increased with age for most of these conditions, but idiopathic thrombocytopenia demonstrated a bimodal distribution with incidence peaks at 0-19 years and [≥]60 years. ConclusionsOur estimated background rates help to contextualize observed events of these potential adverse events of special interest and to detect potential safety signals related to COVID-19 vaccines. Strengths and limitations of this study[tpltrtarr] Recent background rates of selected thromboembolic and coagulation disorders that are potential adverse events special interest related to COVID-19 vaccine are estimated. [tpltrtarr]Background rates during five pre-pandemic (2015-2019) years and 2020 will provide context for these events to identify vaccine safety signals. [tpltrtarr]We used recorded diagnostic codes in administrative data without information on clinical and/or diagnostic confirmation, and the validity of these data are imperfect, which may result in under or overestimation.
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BackgroundNursing 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. MethodsWe observed outcomes among NH residents 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. ResultsFrom 2010-2019, 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<0.05). ConclusionWe 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.
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BackgroundOptimizing the public health response to reduce coronavirus disease 2019 (COVID-19) burden necessitates characterizing population-level heterogeneity of COVID-19 risks. However, heterogeneity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing may introduce biased estimates depending on analytic design. MethodsWe explored the potential for collider bias and characterized individual, environmental, and social determinants of testing and diagnosis using cross-sectional analyses among 14.7 million community-dwelling people in Ontario, Canada. Among those diagnosed, we used separate analytic designs to compare predictors of: 1) individuals testing positive versus negative; 2) symptomatic individuals only testing positive versus testing negative; and 3) individuals testing positive versus individuals not testing positive (i.e., testing negative or not being tested). Analyses included tests conducted between March 1 and June 20, 2020. ResultsOf a total of 14,695,579 individuals, 758,691 were tested for SARS-CoV-2, of whom 25,030 (3.3%) tested positive. The further the odds of testing from the null, the more variability observed in the odds of diagnosis across analytic design, particularly among individual factors. There was less variability in testing by social determinants across analytic designs. Residing in areas with highest household density (adjusted odds ratio [aOR]: 1.86; 95%CI: 1.75-1.98), highest proportion of essential workers (aOR: 1.58; 95%CI: 1.48-1.69), lowest educational attainment (aOR: 1.33; 95%CI: 1.26-1.41), and highest proportion of recent immigrants (aOR: 1.10; 95%CI: 1.05-1.15) were consistently related to increased odds of SARS-CoV-2 diagnosis regardless of analytic design. InterpretationWhere testing is limited, risk factors may be better estimated using population comparators rather than test-negative comparators. Optimizing COVID-19 responses necessitates investment and sufficient coverage of structural interventions tailored to heterogeneity in social determinants of risk, including household crowding, occupation, and structural racism.
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BackgroundWe compared the risk of, testing for, and death following COVID-19 infection across three settings (long-term care homes (LTCH), shelters, the rest of the population) in the Greater Toronto Area (GTA), Canada. MethodsWe sourced person-level data from COVID-19 surveillance and reporting systems in Ontario, and examined settings with population-specific denominators (LTCH residents, shelters, and the rest of the population). We calculated cumulatively, the diagnosed cases per capita, proportion tested for COVID-19, daily and cumulative positivity, and case fatality proportion. We estimated the age- and sex-adjusted relative rate ratios for test positivity and case fatality using quasi-Poisson regression. ResultsBetween 01/23/2020-05/25/2020, we observed a shift in the proportion of cases: from travel-related and into LTCH and shelters. Cumulatively, compared to the rest of the population, the number of diagnosed cases per 100,000 was 59-fold and 18-fold higher among LTCH and shelter residents, respectively. By 05/25/2020, 77.2% of LTCH residents compared to 2.4% of the rest of the population had been tested. After adjusting for age and sex, LTCH residents were 2.5 times (95% confidence interval (CI): 2.3-2.8) more likely to test positive. Case fatality was 26.3% (915/3485), 0.7% (3/402), and 3.6% (506/14133) among LTCH residents, shelter population, and others in the GTA, respectively. After adjusting for age and sex, case fatality was 1.4-fold (95%CI: 1.1-1.9) higher among LTCH residents than the rest of the population. InterpretationHeterogeneity across micro-epidemics among specific populations in specific settings may reflect underlying heterogeneity in transmission risks, necessitating setting-specific COVID-19 prevention and mitigation strategies.