Comparative mRNA booster effectiveness against death or hospitalization with COVID-19 pneumonia across at-risk US Veteran populations.

Studies of comparative mRNA booster effectiveness among high-risk populations can inform mRNA booster-specific guidelines. The study emulated a target trial of COVID-19 vaccinated U.S. Veterans who received three doses of either mRNA-1273 or BNT162b2 vaccines. Participants were followed for up to 32 weeks between July 1, 2021 to May 30, 2022. Non-overlapping populations were average and high risk; high-risk sub-groups were age ≥65 years, high-risk co-morbid conditions, and immunocompromising conditions. Of 1,703,189 participants, 10.9 per 10,000 persons died or were hospitalized with COVID-19 pneumonia over 32 weeks (95% CI: 10.2, 11.8). Although relative risks of death or hospitalization with COVID-19 pneumonia were similar across at-risk groups, absolute risk varied when comparing three doses of BNT162b2 with mRNA-1273 (BNT162b2 minus mRNA-1273) between average-risk and high-risk populations, confirmed by the presence of additive interaction. The risk difference of death or hospitalization with COVID-19 pneumonia for high-risk populations was 2.2 (0.9, 3.6). Effects were not modified by predominant viral variant. In this work, the risk of death or hospitalization with COVID-19 pneumonia over 32 weeks was lower among high-risk populations who received three doses of mRNA-1273 vaccine instead of BNT162b2 vaccine; no difference was found among the average-risk population and age >65 sub-group.

Sex-Based Differences in Severe Outcomes, Including Cardiovascular Hospitalization, in Adults With COVID-19 in Ontario, Canada.

Background: While men have experienced higher risks of SARS-CoV-2 infection compared to women, an analysis of sex differences by age in severe outcomes during the acute phase of infection is lacking. Objectives: The purpose of this study was to assess heterogeneity in severe outcome risks by age and sex by conducting a retrospective cohort study of community-dwelling adults in Ontario who tested positive for SARS-CoV-2 infection during the first 3 waves. Methods: Adjusted odds ratios were estimated using multilevel multivariable logistic regression models including an interaction term for age and sex. The primary outcome was a composite of severe outcomes (hospitalization for a cardiovascular (CV) event, intensive care unit admission, mechanical ventilation, or death) within 30 days. Results: Among 30,736, 199,132, and 186,131 adults who tested positive during the first 3 waves, 1,908 (6.2%), 5,437 (2.7%), and 5,653 (3.0%) experienced a severe outcome within 30 days. For all outcomes, the sex-specific risk depended on age (all P for interaction <0.05). Men with SARS-CoV-2 infection experienced a higher risk of outcomes than infected women of the same age, except for the risk of all-cause hospitalization being higher for young women than men (ages 18-45 years) during waves 2 and 3. The sex disparity in CV hospitalization across all ages either persisted or increased with each subsequent wave. Conclusions: To mitigate risks in subsequent waves, it is helpful to further understand the factors that contribute to the generally higher risks faced by men across all ages, and the persistent or increasing sex disparity in the risk of CV hospitalization.

COVID-19 Vaccine Effectiveness Against Omicron Infection and Hospitalization

OBJECTIVES: This study aimed to provide real-world evidence on coronavirus disease 2019 vaccine effectiveness (VE) against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years. METHODS: We used the test-negative study design and linked provincial databases to estimate BNT162b2 vaccine effectiveness against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years between January 2 and August 27, 2022 in Ontario. We used multivariable logistic regression to estimate VE by time since the latest dose, compared with unvaccinated children, and we evaluated VE by dosing interval. RESULTS: We included 6284 test-positive cases and 8389 test-negative controls. VE against symptomatic infection declined from 24% (95% confidence interval [CI], 8% to 36%) 14 to 29 days after a first dose and 66% (95% CI, 60% to 71%) 7 to 29 days after 2 doses. VE was higher for children with dosing intervals of ≥56 days (57% [95% CI, 51% to 62%]) than 15 to 27 days (12% [95% CI, - 11% to 30%]) and 28 to 41 days (38% [95% CI, 28% to 47%]), but appeared to wane over time for all dosing interval groups. VE against severe outcomes was 94% (95% CI, 57% to 99%) 7 to 29 days after 2 doses and declined to 57% (95%CI, -20% to 85%) after ≥120 days. CONCLUSIONS: In children aged 5 to 11 years, 2 doses of BNT162b2 provide moderate protection against symptomatic Omicron infection within 4 months of vaccination and good protection against severe outcomes. Protection wanes more rapidly for infection than severe outcomes. Overall, longer dosing intervals confer higher protection against symptomatic infection, however protection decreases and becomes similar to shorter dosing interval starting 90 days after vaccination.

Effectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes.

We estimated the effectiveness of booster doses of monovalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults in Ontario, Canada. We used a test-negative design to estimate vaccine effectiveness (VE) against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years from January 2 to October 1, 2022, stratified by age and time since vaccination. We also compared VE during BA.1/BA.2 and BA.4/BA.5 sublineage predominance. We included 11,160 cases and 62,880 tests for test-negative controls. Depending on the age group, compared to unvaccinated adults, VE was 91-98% 7-59 days after a third dose, waned to 76-87% after ≥240 days, was restored to 92-97% 7-59 days after a fourth dose, and waned to 86-89% after ≥120 days. VE was lower and declined faster during BA.4/BA.5 versus BA.1/BA.2 predominance, particularly after ≥120 days. Here we show that booster doses of monovalent mRNA COVID-19 vaccines restored strong protection against severe outcomes for at least 3 months after vaccination. Across the entire study period, protection declined slightly over time, but waned more during BA.4/BA.5 predominance.

Estimated Effectiveness of Postpartum Maternal Messenger RNA COVID-19 Vaccination Against Delta and Omicron SARS-CoV-2 Infection and Hospitalization in Infants Younger Than 6 Months.

This case-control study estimates the effectiveness of maternal postpartum messenger RNA (mRNA) COVID-19 vaccination against Delta and Omicron SARS-CoV-2 infection and hospitalization in infants younger than 6 months.

COVID-19 Vaccine Effectiveness Against Omicron Infection and Hospitalization.

OBJECTIVES: This study aimed to provide real-world evidence on coronavirus disease 2019 vaccine effectiveness (VE) against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years. METHODS: We used the test-negative study design and linked provincial databases to estimate BNT162b2 vaccine effectiveness against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years between January 2 and August 27, 2022 in Ontario. We used multivariable logistic regression to estimate VE by time since the latest dose, compared with unvaccinated children, and we evaluated VE by dosing interval. RESULTS: We included 6284 test-positive cases and 8389 test-negative controls. VE against symptomatic infection declined from 24% (95% confidence interval [CI], 8% to 36%) 14 to 29 days after a first dose and 66% (95% CI, 60% to 71%) 7 to 29 days after 2 doses. VE was higher for children with dosing intervals of ≥56 days (57% [95% CI, 51% to 62%]) than 15 to 27 days (12% [95% CI, -11% to 30%]) and 28 to 41 days (38% [95% CI, 28% to 47%]), but appeared to wane over time for all dosing interval groups. VE against severe outcomes was 94% (95% CI, 57% to 99%) 7 to 29 days after 2 doses and declined to 57% (95%CI, -20% to 85%) after ≥120 days. CONCLUSIONS: In children aged 5 to 11 years, 2 doses of BNT162b2 provide moderate protection against symptomatic Omicron infection within 4 months of vaccination and good protection against severe outcomes. Protection wanes more rapidly for infection than severe outcomes. Overall, longer dosing intervals confer higher protection against symptomatic infection, however protection decreases and becomes similar to shorter dosing interval starting 90 days after vaccination.

Differential patterns by area-level social determinants of health in COVID-19 related mortality and non-COVID-19 mortality: a population-based study of 11.8 million people in Ontario, Canada.

BACKGROUND: Social determinants of health (SDOH) have been associated with COVID-19 outcomes. We examined differential patterns in COVID-19-related mortality by SDOH accounting for confounders and compared these patterns to those for non-COVID-19 mortality. METHODS: Residents of Ontario, Canada aged ≥20 years were followed from March-01-2020 to March-02-2021. COVID-19-related death was defined as death within [-7,30] days of a positive COVID-19 test. Area-level SDOH from 2016 Census included: median household income; proportion with diploma or higher educational-attainment; proportion essential workers, racially-minoritised groups, recent immigrants, apartment buildings, and high-density housing; and average household size. We examined associations between SDOH and COVID-19-related mortality using cause-specific hazard models, treating non-COVID-19 mortality as competing risks, and vice-versa. RESULTS: Of 11,810,255 individuals, we observed 3,880(0.03%) COVID-19-related deaths and 88,107(0.75%) non-COVID-19 deaths. After accounting for individual-level demographics, baseline health, and other area-level SDOH, the following area-level SDOH were associated with increased hazards of COVID-19-related death (hazard ratios[95% confidence intervals]: lower income (1.30[1.04-1.62]), lower educational-attainment (1.27[1.07-1.52]), higher proportions essential workers (1.28[1.05-1.57]), racially-minoritised groups (1.42[1.08-1.87]), apartment buildings (1.25[1.07-1.46]), and large vs. medium household size (1.30[1.12-1.50]). In comparison, areas with higher proportion racially-minoritised groups were associated with a lower hazard of non-COVID-19 mortality (0.88[0.84-0.92]). CONCLUSIONS: Area-level SDOH are associated with COVID-19-related mortality after accounting for demographic and clinical factors. COVID-19 has reversed patterns of lower non-COVID-19 mortality among racially-minoritised groups vs. their counterparts. Pandemic responses should include strategies (e.g., 'hotspot' and risk-group tailored vaccination) to address disproportionate risks and inequitable reach of, and access to, preventive interventions associated with SDOH.

Comorbidity-stratified estimates of 30-day mortality risk by age for unvaccinated men and women with COVID-19: a population-based cohort study.

BACKGROUND: The mortality risk following COVID-19 diagnosis in men and women with common comorbidities at different ages has been difficult to communicate to the general public. The purpose of this study was to determine the age at which unvaccinated men and women with common comorbidities have a mortality risk which exceeds that of 75- and 65-year-old individuals in the general population (Phases 1b/1c thresholds of the Centre for Disease Control Vaccine Rollout Recommendations) following COVID-19 infection during the first wave. METHODS: We conducted a population-based retrospective cohort study using linked administrative datasets in Ontario, Canada. We identified all community-dwelling adults diagnosed with COVID-19 between January 1 and October 31st, 2020. Exposures of interest were age (modelled using restricted cubic splines) and the following conditions: major cardiovascular disease (recent myocardial infarction or lifetime history of heart failure); 2) diabetes; 3) hypertension; 4) recent cancer; 5) chronic obstructive pulmonary disease; 6) Stages 4/5 chronic kidney disease (CKD); 7) frailty. Logistic regression in the full cohort was used to estimate the risk of 30-day mortality for 75- and 65-year-old individuals. Analyses were repeated after stratifying by sex and medical condition to determine the age at which 30-day morality risk in strata exceed that of the general population at ages 65 and 75 years. RESULTS: We studied 52,429 individuals (median age 42 years; 52.5% women) of whom 417 (0.8%) died within 30 days. The 30-day mortality risk increased with age, male sex, and comorbidities. The 65- and 75-year-old mortality risks in the general population were exceeded at the youngest age by people with CKD, cancer, and frailty. Conversely, women aged < 65 years who had diabetes or hypertension did not have higher mortality than 65-year-olds in the general population. Most people with medical conditions (except for Stage 4-5 CKD) aged < 45 years had lower predicted mortality than the general population at age 65 years. CONCLUSION: The mortality risk in COVID-19 increases with age and comorbidity but the prognostic implications varied by sex and condition. These observations can support communication efforts and inform vaccine rollout in jurisdictions with limited vaccine supplies.

Maternal mRNA covid-19 vaccination during pregnancy and delta or omicron infection or hospital admission in infants: test negative design study.

OBJECTIVE: To estimate the effectiveness of maternal mRNA covid-19 vaccination during pregnancy against delta and omicron severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and hospital admission in infants. DESIGN: Test negative design study. SETTING: Community and hospital testing in Ontario, Canada. PARTICIPANTS: Infants younger than six months of age, born between 7 May 2021 and 31 March 2022, who were tested for SARS-CoV-2 between 7 May 2021 and 5 September 2022. INTERVENTION: Maternal mRNA covid-19 vaccination during pregnancy. MAIN OUTCOME MEASURES: Laboratory confirmed delta or omicron infection or hospital admission of the infant. Multivariable logistic regression estimated vaccine effectiveness, with adjustments for clinical and sociodemographic characteristics associated with vaccination and infection. RESULTS: 8809 infants met eligibility criteria, including 99 delta cases (4365 controls) and 1501 omicron cases (4847 controls). Infant vaccine effectiveness from two maternal doses was 95% (95% confidence interval 88% to 98%) against delta infection and 97% (73% to 100%) against infant hospital admission due to delta and 45% (37% to 53%) against omicron infection and 53% (39% to 64%) against hospital admission due to omicron. Vaccine effectiveness for three doses was 73% (61% to 80%) against omicron infection and 80% (64% to 89%) against hospital admission due to omicron. Vaccine effectiveness for two doses against infant omicron infection was highest with the second dose in the third trimester (53% (42% to 62%)) compared with the first (47% (31% to 59%)) or second (37% (24% to 47%)) trimesters. Vaccine effectiveness for two doses against infant omicron infection decreased from 57% (44% to 66%) between birth and eight weeks to 40% (21% to 54%) after 16 weeks of age. CONCLUSIONS: Maternal covid-19 vaccination with a second dose during pregnancy was highly effective against delta and moderately effective against omicron infection and hospital admission in infants during the first six months of life. A third vaccine dose bolstered protection against omicron. Effectiveness for two doses was highest with maternal vaccination in the third trimester, and effectiveness decreased in infants beyond eight weeks of age.

Post-acute health care burden after SARS-CoV-2 infection: a retrospective cohort study.

BACKGROUND: The post-acute burden of health care use after SARS-CoV-2 infection is unknown. We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario by comparing those with positive and negative polymerase chain reaction (PCR) test results for SARS-CoV-2 infection. METHODS: We conducted a retrospective cohort study involving community-dwelling adults in Ontario who had a PCR test between Jan. 1, 2020, and Mar. 31, 2021. Follow-up began 56 days after PCR testing. We matched people 1:1 on a comprehensive propensity score. We compared per-person-year rates for health care encounters at the mean and 99th percentiles, and compared counts using negative binomial models, stratified by sex. RESULTS: Among 531 702 matched people, mean age was 44 (standard deviation [SD] 17) years and 51% were female. Females who tested positive for SARS-CoV-2 had a mean of 1.98 (95% CI 1.63 to 2.29) more health care encounters overall per-person-year than those who had a negative test result, with 0.31 (95% CI 0.05 to 0.56) more home care encounters to 0.81 (95% CI 0.69 to 0.93) more long-term care days. At the 99th percentile per-person-year, females who tested positive had 6.48 more days of hospital admission and 28.37 more home care encounters. Males who tested positive for SARS-CoV-2 had 0.66 (95% CI 0.34 to 0.99) more overall health care encounters per-person-year than those who tested negative, with 0.14 (95% CI 0.06 to 0.21) more outpatient encounters and 0.48 (95% CI 0.36 to 0.60) long-term care days, and 0.43 (95% CI -0.67 to -0.21) fewer home care encounters. At the 99th percentile, they had 8.69 more days in hospital per-person-year, with fewer home care (-27.31) and outpatient (-0.87) encounters. INTERPRETATION: We found significantly higher rates of health care use after a positive SARS-CoV-2 PCR test in an analysis that matched test-positive with test-negative people. Stakeholders can use these findings to prepare for health care demand associated with post-COVID-19 condition (long COVID).

Telemedicine use and outcomes after transient ischemic attack and minor stroke during the COVID-19 pandemic: a population-based cohort study.

BACKGROUND: The COVID-19 pandemic has led to an increase in telemedicine use. We compared care and outcomes in patients with transient ischemic attack (TIA) or minor ischemic stroke before and after the widespread adoption of telemedicine in Ontario, Canada, in 2020. METHODS: In a population-based cohort study using linked administrative data, we identified patients with TIA or ischemic stroke discharged from any emergency department in Ontario before the widespread use of telemedicine (Apr. 1, 2015, to Mar. 31, 2020) and after (Apr. 1, 2020, to Mar. 31, 2021). We measured care, including visits with a physician, investigations and medication renewal. We compared 90-day death before and after 2020 using Cox proportional hazards models, and we compared 90-day admission using cause-specific hazard models. RESULTS: We identified 47 601 patients (49.3% female; median age 73, interquartile range 62-82, yr) with TIA (n = 35 695, 75.0%) or ischemic stroke (n = 11 906, 25.0%). After 2020, 83.1% of patients had 1 or more telemedicine visit within 90 days of emergency department discharge, compared with 3.8% before. The overall access to outpatient visits within 90 days remained unchanged (92.9% before v. 94.0% after; risk difference 1.1, 95% confidence interval [CI] -1.3 to 3.5). Investigations and medication renewals were unchanged. Clinical outcomes were also similar before and after 2020; the adjusted hazard ratio was 0.97 (95% CI 0.91 to 1.04) for 90-day all-cause admission, 1.06 (95% CI 0.94 to 1.20) for stroke admission and 1.07 (95% CI 0.93 to 1.24) for death. INTERPRETATION: Care and short-term outcomes after TIA or minor stroke remained stable after the widespread implementation of telemedicine during the COVID-19 pandemic. Our findings suggest that telemedicine is an effective method of health care delivery that can be complementary to in-person care for minor ischemic cerebrovascular events.

Effectiveness of COVID-19 Vaccines Over Time Prior to Omicron Emergence in Ontario, Canada: Test-Negative Design Study.

Background: Waning protection from 2 doses of coronavirus disease 2019 (COVID-19) vaccines led to third dose availability in multiple countries even before the emergence of the Omicron variant. Methods: We used the test-negative study design to estimate vaccine effectiveness (VE) against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, any symptomatic infection, and severe outcomes (COVID-19-related hospitalizations or death) by time since second dose of any combination of BNT162b2, mRNA-1273, and ChAdOx1 between January 11, and November 21, 2021, for subgroups based on patient and vaccine characteristics. Results: We included 261 360 test-positive cases (of any SARS-CoV-2 lineage) and 2 783 699 individuals as test-negative controls. VE of 2 mRNA vaccine doses decreased from 90% (95% CI, 90%-90%) 7-59 days after the second dose to 75% (95% CI, 72%-78%) after ≥240 days against infection, decreased from 94% (95% CI, 84%-95%) to 87% (95% CI, 85%-89%) against symptomatic infection, and remained stable (98% [95% CI, 97%-98%] to 98% [95% CI, 96%-99%]) against severe outcomes. Similar trends were seen with heterologous ChAdOx1 and mRNA vaccine schedules. VE estimates for dosing intervals <35 days were lower than for longer intervals (eg, VE of 2 mRNA vaccines against symptomatic infection at 120-179 days was 86% [95% CI, 85%-88%] for dosing intervals <35 days, 92% [95% CI, 91%-93%] for 35-55 days, and 91% [95% CI, 90%-92%] for ≥56 days), but when stratified by age group and subperiod, there were no differences between dosing intervals. Conclusions: Before the emergence of Omicron, VE of any 2-dose primary series, including heterologous schedules and varying dosing intervals, decreased over time against any infection and symptomatic infection but remained high against severe outcomes.

Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes.

Importance: The 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. Objective: To 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 Participants: This 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. Exposures: Receipt of 2 or 3 doses of the COVID-19 vaccine and time since last dose. Main Outcomes and Measures: The 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%. Results: Of 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 Relevance: In 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.

Relationship of frailty with excess mortality during the COVID-19 pandemic: a population-level study in Ontario, Canada.

BACKGROUND: There is a paucity of the literature on the relationship between frailty and excess mortality due to the COVID-19 pandemic. METHODS: The entire community-dwelling adult population of Ontario, Canada, as of January 1st, 2018, was identified using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort. Residents of long-term care facilities were excluded. Frailty was categorized through the Johns Hopkins Adjusted Clinical Groups (ACG® System) frailty indicator. Follow-up was until December 31st, 2020, with March 11th, 2020, indicating the beginning of the COVID-19 pandemic. Using multivariable Cox models with patient age as the timescale, we determined the relationship between frailty status and pandemic period on all-cause mortality. We evaluated the modifier effect of frailty using both stratified models as well as incorporating an interaction between frailty and the pandemic period. RESULTS: We identified 11,481,391 persons in our cohort, of whom 3.2% were frail based on the ACG indicator. Crude mortality increased from 0.75 to 0.87% per 100 person years from the pre- to post-pandemic period, translating to ~ 13,800 excess deaths among the community-dwelling adult population of Ontario (HR 1.11 95% CI 1.09-1.11). Frailty was associated with a statistically significant increase in all-cause mortality (HR 3.02, 95% CI 2.99-3.06). However, all-cause mortality increased similarly during the pandemic in frail (aHR 1.13, 95% CI 1.09-1.16) and non-frail (aHR 1.15, 95% CI 1.13-1.17) persons. CONCLUSION: Although frailty was associated with greater mortality, frailty did not modify the excess mortality associated with the pandemic.

Clinical risk, sociodemographic factors, and SARS-CoV-2 infection over time in Ontario, Canada.

We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction < 0.0001). Prior to the first-wave peak, SARS-CoV-2 infection increased with age whereas this association reversed thereafter. Risk factors that persisted included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, hypertension, and diabetes. While there was a reduction in infection rates after mid-April 2020, there was less impact in regions with higher racial/ethnic diversity. Immediately following the initial peak, individuals living in the most racially/ethnically diverse communities with 2, 3, or ≥ 4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P < 0.0001). In the latter half of 2020, this disparity persisted with corresponding ORs of 1.66, 2.48, and 3.70-fold higher, respectively. In the least racially/ethnically diverse communities, there was little/no gradient in infection rates across risk strata. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in the most racially/ethnically diverse communities.

Follow-up after post-partum psychiatric emergency department visits: an equity-focused population-based study in Canada.

BACKGROUND: Emergency department visits for a psychiatric reason in the post-partum period represent an acute need for mental health care at a crucial time, but little is known about the extent of timely outpatient follow-up after these visits or how individual and intersecting social determinants of health influence this outcome. This study aimed to examine outpatient mental health care follow-up by a physician in the 30 days after an individual attended the emergency department for a psychiatric reason in the post-partum period and understand how social determinants of health affect who receives follow-up care. METHODS: In this population-based cohort study, routinely collected health data from Ontario, Canada were accessed through ICES to identify all post-partum individuals whose sex was listed as female on their health card and who had attended an emergency department in Ontario before the COVID-19 pandemic for a psychiatric reason. Individuals admitted to hospital at the time of the emergency department visit, who died during the visit, or who left without being seen were excluded from the study. Ethnicity data for individuals were not collected. The primary outcome was the proportion of individuals with any outpatient physician (psychiatrist or family physician) visit for a mental health reason within 30 days of the index emergency department visit. Family physician mental health visits were identified using a validated algorithm for Ontario Health Insurance Plan-billed visits and mental health diagnostic codes for community health centre visits. We examined the associations between social determinants of health (age, neighbourhood income, community size, immigration, neighbourhood ethnic diversity) and who received an outpatient mental health visit. We used modified Poisson regression adjusting for the other social determinants of health, clinical, and health services characteristics to examine independent associations with follow-up, and conditional inference trees to explore how social determinants of health intersect with each other and with clinical and health services characteristics in relation to follow-up. FINDINGS: We analysed data collected between April 1, 2008, and March 10, 2020, after exclusions we identified 12 158 people who had attended the emergency department for a psychiatric reason in the post-partum period (mean age 26·9 years [SD 6·2]; range 13-47); 9848 individuals lived in an urban area, among these 1518 (15·5%) were immigrants and 2587 (26·3%) lived in areas with high ethnic diversity. 5442 (44·8%) of 12 158 individuals received 30-day follow-up. In modified Poisson regression models, younger age, lower neighbourhood income, smaller community size, and being an immigrant were associated with a lower likelihood of follow-up. In the CTREE, similar variables were important, with several intersections between social determinants of health and between social determinants of health and other variables. INTERPRETATION: Fewer than half of emergency department visits for a psychiatric reason in the post-partum period were followed by timely outpatient care, with social-determinants-of-health-based disparities in access to care. Improvements in equitable access to post-emergency department mental health care are urgently needed in this high-risk post-partum population. FUNDING: Department of Psychiatry, University of Toronto; Canadian Institutes of Health Research.

Effectiveness of COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe outcomes with variants of concern in Ontario.

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

Trends in Health Service Use for Canadian Adults With Dementia and Parkinson Disease During the First Wave of the COVID-19 Pandemic.

Importance: Persons with dementia and Parkinson disease (PD) are vulnerable to disruptions in health care and services. Objective: To examine changes in health service use among community-dwelling persons with dementia, persons with PD, and older adults without neurodegenerative disease during the first wave of the COVID-19 pandemic. Design Setting and Participants: Repeated cross-sectional analysis using population-based administrative data among community-dwelling persons with dementia, persons with PD, and adults 65 years and older at the start of each week from March 1 through the week of September 20, 2020 (pandemic period), and March 3 through the week of September 22, 2019 (historical period), in Ontario, Canada. Exposures: COVID-19 pandemic as of March 1, 2020. Main Outcomes and Measures: Main outcomes were weekly rates of emergency department visits, hospitalizations, nursing home admissions, home care, virtual and in-person physician visits, and all-cause mortality. Poisson regression models were used to calculate weekly rate ratios (RRs) with 95% CIs comparing pandemic weeks with historical levels. Results: Among those living in the community as of March 1, 2020, persons with dementia (n = 131 466; mean [SD] age, 80.1 [10.1] years) were older than persons with PD (n = 30 606; 73.7 [10.2] years) and older adults (n = 2 363 742; 74.0 [7.1] years). While all services experienced declines, the largest drops occurred in nursing home admissions (RR for dementia: 0.10; 95% CI, 0.07-0.15; RR for PD: 0.03; 95% CI, 0.00-0.21; RR for older adults: 0.11; 95% CI, 0.06-0.18) and emergency department visits (RR for dementia: 0.45; 95% CI, 0.41-0.48; RR for PD: 0.40; 95% CI, 0.34-0.48; RR for older adults: 0.45; 95% CI, 0.44-0.47). After the first wave, most services returned to historical levels except physician visits, which remained elevated (RR for dementia: 1.07; 95% CI, 1.05-1.09; RR for PD: 1.10, 95% CI, 1.06-1.13) and shifted toward virtual visits. Older adults continued to experience lower hospitalizations. All-cause mortality was elevated across cohorts. Conclusions and Relevance: In this population-based repeated cross-sectional study in Ontario, Canada, those with dementia, those with PD, and older adults sought hospital care far less than usual, were not admitted to nursing homes, and experienced excess mortality during the first wave of the pandemic. Most services returned to historical levels, but virtual physician visits remained a feature of care. While issues of equity and quality of care are still emerging among persons with neurodegenerative diseases, policies to support virtual care are necessary.

Factors associated with SARS-CoV-2 test positivity in long-term care homes: A population-based cohort analysis using machine learning.

BACKGROUND: SARS-Cov-2 infection rates are high among residents of long-term care (LTC) homes. We used machine learning to identify resident and community characteristics predictive of SARS-Cov-2 infection. METHODS: We linked 26 population-based health and administrative databases to identify the population of all LTC residents tested for SARS-Cov-2 infection in Ontario, Canada. Using ensemble-based algorithms, we examined 484 factors, including individual-level demographics, healthcare use, comorbidities, functional status, and laboratory results; and community-level characteristics to identify factors predictive of infection. Analyses were performed separately for January to April (early wave 1) and May to August (late wave 1). FINDINGS: Among 80,784 LTC residents, 64,757 (80.2%) were tested for SARS-Cov-2 (median age 86 (78-91) years, 30.6% male), of whom 10.2% of 33,519 and 5.2% of 31,238 tested positive in early and late wave 1, respectively. In the late phase (when restriction of visitors, closure of communal spaces, and universal masking in LTC were routine), regional-level characteristics comprised 33 of the top 50 factors associated with testing positive, while laboratory values and comorbidities were also predictive. The c-index of the final model was 0.934, and sensitivity was 0.887. In the highest versus lowest risk quartiles, the odds ratio for infection was 114.3 (95% CI 38.6-557.3). LTC-related geographic variations existed in the distribution of observed infection rates and the proportion of residents at highest risk. INTERPRETATION: Machine learning informed evaluation of predicted and observed risks of SARS-CoV-2 infection at the resident and LTC levels, and may inform initiatives to improve care quality in this setting. FUNDING: Funded by a Canadian Institutes of Health Research, COVID-19 Rapid Research Funding Opportunity grant (# VR4 172736) and a Peter Munk Cardiac Centre Innovation Grant. Dr. D. Lee is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. Dr. Austin is supported by a Mid-Career investigator award from the Heart and Stroke Foundation. Dr. McAlister is supported by an Alberta Health Services Chair in Cardiovascular Outcomes Research. Dr. Kaul is the CIHR Sex and Gender Science Chair and the Heart & Stroke Chair in Cardiovascular Research. Dr. Rochon holds the RTO/ERO Chair in Geriatric Medicine from the University of Toronto. Dr. B. Wang holds a CIFAR AI chair at the Vector Institute.