Social inequalities in COVID-19 deaths by area-level income: patterns over time and the mediating role of vaccination in a population of 11.2 million people in Ontario, Canada (preprint)

ImportanceSocial inequalities in COVID-19 deaths were evident early in the pandemic. Less is known about how vaccination may have influenced inequalities in COVID-19 deaths. ObjectivesTo examine patterns in COVID-19 deaths by area-level income over time and to examine the impact of vaccination on inequality patterns in COVID-19 deaths. Design, setting, and participantsPopulation-based retrospective cohort study including community-living individuals aged [≥]18 years residing in Ontario, Canada, as of March 1, 2020 who were followed through to January 30, 2022 (five pandemic waves). ExposureArea-level income derived from the 2016 Census at the level of dissemination area categorized into quintiles. Vaccination defined as receiving [≥] 1 dose of Johnson-Johnson vaccine or [≥] 2 doses of other vaccines. Main outcome measuresCOVID-19 death defined as death within 30 days following, or 7 days prior to a positive SARS-CoV-2 PCR test. Cause-specific hazard models were used to examine the relationship between income and COVID-19 deaths in each wave. We used regression-based causal mediation analyses to examine the impact of vaccination in the relationship between income and COVID-19 deaths during waves four and five. ResultsOf 11,248,572 adults, 7044 (0.063%) experienced a COVID-19 death. After accounting for demographics, baseline health, and area-level social determinants of health, inequalities in COVID-19 deaths by income persisted over time (adjusted hazard ratios (aHR) [95% confidence intervals] comparing lowest-income vs. highest-income quintiles were 1.37[0.98-1.92] for wave one, 1.21[0.99-1.48] for wave two, 1.55[1.22-1.96] for wave three, and 1.57[1.15-2.15] for waves four and five). Of 11,122,816 adults alive by the start of wave four, 7,534,259(67.7%) were vaccinated, with lower odds of vaccination in the lowest-income compared to highest-income quintiles (0.71[0.70-0.71]). This inequality in vaccination accounted for 57.9%[21.9%-94.0%] of inequalities in COVID-19 deaths between individuals in the lowest-income vs. highest-income quintiles. ConclusionsInequalities by income persisted in COVID-19 deaths over time. Efforts are needed to address both vaccination gaps and residual heightened risks associated with lower income to improve health equity in COVID-19 outcomes. Summary boxO_ST_ABSSection 1: What is already known on this topicC_ST_ABSO_LIEmerging data suggest social inequalities in COVID-19 deaths might have persisted over time, but existing studies were limited by their ecological design and/or inability to account for potential confounders. C_LIO_LIVaccination has contributed to reducing COVID-19 deaths but there were social inequalities in vaccination coverage. C_LIO_LIThe impact of inequalities in vaccination on inequalities in COVID-19 deaths has not yet been well-studied. C_LI Section 2: What this study addsO_LIAcross five pandemic waves (2020-2021) in Ontario, Canada, COVID-19 deaths remained higher in individuals living in lower-income neighbourhoods, even after accounting for individual-level demographics and baseline health, and other area-level social determinants of health. C_LIO_LIDuring later waves (following the vaccination roll-out), over half (57.9%) of the inequalities in COVID-19 deaths between individuals living in the lowest and highest income neighbourhoods could be attributed to differential vaccination coverage by income. This means that if vaccine equality was achieved, inequalities in deaths would persist but be reduced. C_LIO_LIAddressing vaccination gaps, as well as addressing the residual heightened risks of COVID-19 associated with lower income could improve health equity in COVID-19 outcomes. C_LI

Predictors of all-cause mortality among patients hospitalized with influenza, respiratory syncytial virus, or SARS-CoV-2 (preprint)

Background: Identification of shared and divergent predictors of clinical severity across respiratory viruses may support clinical decision-making and resource planning in the context of a novel or re-emergent respiratory pathogen. Methods: We 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 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. Results: 3,186 (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. Common 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. Conclusions: Our findings may help identify patients at highest risk of illness secondary to a respiratory virus, anticipate hospital resource needs, and prioritize local preventions and therapeutics to communities with high prevalence of risk factors.

Area-level social and structural inequalities determine mortality related to COVID-19 diagnosis in Ontario, Canada: a population-based explanatory modeling study of 11.8 million people (preprint)

Importance: Social 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. Objectives: To 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 participants: Population-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. Exposure: SDOH 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 measures: COVID-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. Results: Of 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 relevance: Area-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.

Background incidence rates of adverse events of special interest related to COVID-19 vaccines in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance (preprint)

Background: Background 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. Methods: We 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. Results: The 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 and older for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age. Conclusions: Our estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Epidemiology of myocarditis and pericarditis following mRNA vaccines in Ontario, Canada: by vaccine product, schedule and interval (preprint)

Importance Increased 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. Objective The 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. Design We 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. Setting This study was conducted in Ontario, Canada (population: 14.7 million) using the provincial COVID-19 vaccine registry and provincial adverse events following immunization database. Participants We 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. Exposure Receipt 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. Results There 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 Relevance Our 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.

Stringency of Containment and Closures on the Growth of SARS-CoV-2 in Canada prior to Accelerated Vaccine Roll-Out (preprint)

Background: Many studies have examined the effectiveness of non-pharmaceutical interventions (NPIs) on SARS-CoV-2 transmission worldwide. However, less attention has been devoted to understanding the limits of NPIs across the course of the pandemic and along a continuum of their stringency. In this study, we explore the relationship between the growth of SARS-CoV-2 cases and a stringency index across Canada prior to accelerated vaccine roll-out.Methods: We conducted an ecological time-series study of daily SARS-CoV-2 case growth in Canada from February 2020 to February 2021. Our outcome was a back-projected version of the daily growth ratio in a stringency period (i.e., a 10-point range of the stringency index) relative to the last day of the previous period. We examined the trends in case growth using a linear mixed effects model accounting for stringency period, province, and mobility in public domains.Results: Case growth declined, rapidly, by 37–50% and began plateauing within the first two weeks of the first wave, irrespective of the starting values of the stringency index. Across individual stringency periods, there was a lag of 11·3 days, on average, to observe the largest cumulative decline in relative growth. The largest decreasing trends from our mixed effects model occurred over the first stringency period in each province, at a mean index value of 25·2 out of 100.Conclusions: There was a negative correlation between NPI stringency and growth of SARS-CoV-2 that attenuated throughout the course of Canada’s epidemic. We suggest that individual- and network-level risk factors need to guide the use of NPIs in future epidemics.

Effectiveness of COVID-19 vaccines against variants of concern, Canada (preprint)

Objectives: To estimate the effectiveness of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and ChAdOx1 (AstraZeneca) vaccines against symptomatic SARS-CoV-2 infection and severe outcomes (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) variants of concern (VOCs) during December 2020 to May 2021. Methods: We conducted a test-negative design study using linked population-wide vaccination, laboratory testing, and health administrative databases in Ontario, Canada. Results: Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination ([≥]14 days after dose 1) was higher for mRNA-1273 than BNT162b2 and ChAdOx1. Full vaccination ([≥]7 days after dose 2) increased vaccine effectiveness for BNT162b2 and mRNA-1273 against Alpha. Protection against symptomatic infection caused by Beta/Gamma was lower with partial vaccination for ChAdOx1 than mRNA-1273. Against Delta, vaccine effectiveness after partial vaccination tended to be lower than against Alpha for BNT162b2 and mRNA-1273, but was similar to Alpha for ChAdOx1. Full vaccination with BNT162b2 increased protection against Delta to levels comparable to Alpha and Beta/Gamma. Vaccine effectiveness against hospitalization or death caused by all studied VOCs was generally higher than for symptomatic infection after partial vaccination with all three vaccines. Conclusions: Our findings suggest that even a single dose of these 3 vaccine products provide good to excellent protection against symptomatic infection and severe outcomes caused by the 4 currently circulating variants of concern, and that 2 doses are likely to provide even higher protection.

Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes in Ontario, Canada (preprint)

Objectives: To estimate the effectiveness of one and two doses of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. Design: Using a test-negative design study and linked laboratory, vaccination, and health administrative databases, we estimated adjusted vaccine effectiveness (aVE) against symptomatic infection and severe outcomes (hospitalization or death) using multivariable logistic regression. Setting: Ontario, Canada between 14 December 2020 and 19 April 2021. Participants: Community-dwelling adults aged [≥]16 years who were tested for SARS-CoV-2 and had COVID-19 symptoms. Interventions: Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273 vaccine. Main outcome measures: Laboratory-confirmed SARS-CoV-2 identified by RT-PCR; hospitalization or death associated with SARS-CoV-2 infection. Results: Among 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received 1 or more vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. aVE against symptomatic infection 14 days or more 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. aVE 7 days or more after receiving 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, aVE 14 days or more after receiving 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 or more, whereas aVE 7 days or more after receiving 2 doses was 98% (95%CI, 88 to 100%). For adults aged 70 years and older, aVE estimates were lower after receiving 1 dose, but were comparable to younger adults after 28 days. After 2 doses, we observed high aVE against E484K-positive variants. Conclusions: Two doses of BNT162b2 and mRNA-1273 vaccines are highly effective against both symptomatic infection and severe outcomes. Effectiveness is lower after only a single dose, particularly for older adults shortly after the first dose.

Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines Against Symptomatic SARS-CoV-2 Infection and Severe COVID-19 Outcomes in Ontario, Canada (preprint)

Background: We estimated the effectiveness of BNT162b2 and mRNA-1273 vaccines among residents of Ontario, Canada, where a policy to use an up to 16-week interval between doses was adopted in March 2021.Methods: We conducted a test-negative design study using linked province-wide laboratory, vaccination, and health administrative datasets. We included symptomatic individuals tested for SARS-CoV-2 by RT-PCR between 14 December 2020 and 19 April 2021. Study outcomes included symptomatic infection and associated severe outcomes (hospitalization or death). We estimated adjusted vaccine effectiveness (aVE) using multivariable logistic regression.Findings: Among 324,033 symptomatic tested individuals, 53,270 (16·4%) were positive for SARS-CoV-2 and 21,272 (6·6%) had received ≥1 dose of mRNA vaccine. Among test-positive cases, 2,479 (4·7%) had a severe outcome. aVE against symptomatic infection ≥14 days after receiving only 1 dose was 60% (95%CI, 57–64%), increasing from 48% (95%CI, 41–54%) at 14–20 days after the first dose to 71% (95%CI, 63–78%) at 35–41 days. aVE ≥7 days after receiving 2 doses was 91% (95%CI, 89–93%). Against severe outcomes, aVE ≥14 days after receiving 1 dose was 70% (95%CI, 60–77%) and aVE ≥7 days after receiving 2 doses was 98% (95%CI, 88–100%). We observed lower aVE against both outcomes after receiving 1 dose for adults aged ≥70 years, but aVE estimates for older adults were comparable to younger adults after 28 days. After 2 doses, we observed high aVE against E484K-positive variants.Interpretation: Our findings suggest that 2 doses of BNT162b2 and mRNA-1273 vaccines are highly effective against both symptomatic infection and associated severe outcomes for all circulating variants, with effectiveness lower after only a single dose, particularly for older adults shortly after the first dose.Funding Information: Canadian Institutes of Health Research, Public Health Agency of Canada, Ontario Ministries of Health and Long-Term Care.Declaration of Interests: KW is CEO of CANImmunize and serves on the data safety board for the Medicago COVID-19 vaccine trial. SMM has received unrestricted research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer, and Roche-Assurex for unrelated studies. SMM has received fees as an advisory board member for GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Seqirus. CHR has received an unrestricted research grant from Pfizer for an unrelated study. The other authors declare no conflicts of interest.Ethics Approval Statement: ICES is a prescribed entity under Ontario’s Personal Health Information Protection Act (PHIPA). Section 45 of PHIPA authorizes ICES to collect personal health information, without consent, for the purpose of analysis or compiling statistical information with respect to the management of, evaluation or monitoring of, the allocation of resources to or planning for all or part of the health system. Projects that use data collected by ICES under section 45 of PHIPA, and use no other data, are exempt from REB review. The use of the data in this project is authorized under section 45 and approved by ICES’ Privacy and Legal Office.

Increasing concentration of COVID-19 by socioeconomic determinants and geography in Toronto, Canada: an observational study (preprint)

Background: Inequities in the burden of COVID-19 observed across Canada suggest heterogeneity within community transmission. Objectives: To 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). Design: Retrospective, population-based observational study using surveillance data from Ontario's Case and Contact Management system. Setting: Toronto, Canada. Participants: Laboratory-confirmed cases of COVID-19 (N=33,992). Measurements: We 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. Results: The 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. Limitations: Study 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. Conclusion: COVID-19 is increasingly concentrated by SDOH given socioeconomic inequities and structural racism. Primary Funding Source: Canadian Institutes of Health Research.

Background rates of hospitalizations and emergency department visits for selected thromboembolic and coagulation disorders in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance (preprint)

Objective: The objective of this study was to estimate background rates of selected thromboembolic and coagulation disorders in Ontario, Canada. Design: Population-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). Participants: All Ontario residents. Primary outcome measures: Incidence 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. Results: The 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. Conclusions: Our 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.

Background rates of all-cause mortality, hospitalizations, and emergency department visits among nursing home residents in Ontario, Canada to inform COVID-19 vaccine safety assessments (preprint)

Background. Nursing home (NH) residents have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic and are prioritized for vaccination. NH residents are generally at increased risk of poor outcomes due to advanced age, frailty, and complex health conditions. We report monthly incidence rates of deaths, hospitalizations, and emergency department (ED) visits during ten pre-pandemic years (2010-2019) and 2020 to provide context for assessments of COVID-19 vaccine safety in NH residents. Methods. We observed deaths, hospitalizations, and ED visits among all Ontarians living in NHs using health administrative databases. Monthly incidence rates were calculated by month, by sex, and by age group. Direct comparisons between months were assessed using one-sample t-tests; direct comparisons by age and sex were assessed using chi-squared tests. Results. From January 1, 2010 through December 31, 2019, there were, on average, 83,453 (SD: 652.4) Ontarians living in NHs in any given 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. Mortality rates were higher for men (p<0.001) and residents aged [≥]80 years (p<0.001). Hospitalization and ED visit rates were higher for men but were lower for residents aged [≥]80 years. From January to October 2020, the number of NH residents declined markedly. Mortality rates were increased in 2020 compared to 2010-2019, but hospitalization and ED visit rates were reduced in 2020 compared to 2010-2019 (p<0.001). Conclusion. We identified relatively consistent monthly mortality, hospitalization, and ED visit rates during ten pre-pandemic years. Marked differences in these rates were observed during 2020, coinciding with heightened COID-19 infection rates and restrictions. These results provide context to the assessment of COVID-19 vaccine safety outcomes in this high-risk population.

The Individual and Social Determinants of COVID-19 in Ontario, Canada: A Population-Wide Study (preprint)

Importance: Optimizing 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. Objective: Characterizing individual, environmental, and social determinants of SARS-CoV-2 testing and COVID-19 diagnosis. Design: We conducted cross-sectional analyses among 14.7 million people comparing individual, environmental, and social determinants among individuals who were tested versus not yet tested. Among those diagnosed, we used three analytic designs to compare predictors of: 1) individuals testing positive versus negative; 2) symptomatic individuals testing positive versus 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. Setting: Ontario, Canada. Participants: All individuals with [≥]1 healthcare system contact since March 2012, excluding individuals deceased before, or born after, March 1, 2020, or residing in a long-term care facility. Exposures: Individual-level characteristics (age, sex, underlying health conditions, prior healthcare use), area-based environmental (air pollution) exposures, and area-based social determinants of health (income, education, housing, marital status, race/ethnicity, and recent immigration). Main Outcomes and Measures: Odds of SARS-CoV-2 test, and of COVID-19 diagnosis. Results: Of a total of 14,695,579 individuals, 758,691 had been tested, 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 design. Residing in areas with highest household density (adjusted odds ratio: 2.08; 95%CI: 1.95-1.21), lowest educational attainment (adjusted odds ratio: 1.52; 95%CI: 1.44-1.60), and highest proportion of recent immigrants (adjusted odds ratio: 1.12; 95%CI: 1.07-1.16) were consistently related to increased odds of COVID-19 across analytic designs. Conclusions and Relevance: Where 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 and systemic racism.

Heterogeneity in risk, testing and outcome of COVID-19 across outbreak settings in the Greater Toronto Area, Canada: an observational study (preprint)

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.