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.

Epidemiology of COVID-19 and Its Cardiac and Neurologic Complications Among Chinese and South Asians in Ontario: Waves 1, 2, and 3.

Background: Although we had previously reported the cardiac and neurologic outcomes of Chinese and South Asian Ontarians in wave 1 of COVID-19, data on subsequent waves of COVID-19 remain unexamined. This is an extension study of this cohort in waves 2 and 3. Methods: We identified adult Ontarians with a positive COVID-19 polymerase chain reaction test from January 1, 2020 to June 30, 2021, and they were classified as being Chinese or South Asian using a validated surname algorithm; we compared their outcomes of mortality, and cardiac and neurologic complications with those of the general population using multivariable logistic regression models. Results: Compared to the general population (n = 439,977), the Chinese population (n = 15,208) was older (mean age 44.2 vs 40.6 years, P < 0.001) and the South Asian population (n = 46,333) was younger (39.2 years, P < 0.001). The Chinese population had a higher 30-day mortality (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.61) and more hospitalization or emergency department visits (OR, 1.14; 95% CI, 1.09-1.28), with a trend toward a higher incidence of cardiac complications (OR, 1.03; 95% CI, 0.87-1.12) and neurologic complications (OR, 1.23; 95% CI, 0.96-1.58). South Asians had a lower 30-day mortality (OR, 0.88; 95% CI, 0.78-0.98) but a higher incidence of hospitalization or emergency department visits (OR, 1.17; 95% CI, 1.14-1.20) with a trend toward a lower incidence of cardiac complications (OR, 0.76; 95% CI, 0.67-0.87) and neurologic complications (OR, 0.89; 95% CI, 0.73-1.09). There was also a significant difference in these outcomes between wave 1, 2 and 3, with a greater mortality in all groups in waves 2 and 3. Conclusions: Ethnicity continues to be an important determinant of mortality, cardiac and neurologic outcomes, and healthcare use among patients with COVID-19, requiring further studies to understand factors driving these differences.

Contexte: Nous avons déjà présenté les issues cliniques cardiaques et neurologiques chez les Ontariens de descendance chinoise ou sud-asiatique pour la première vague de la pandémie de COVID-19, mais les données au sujet des vagues ultérieures n'avaient pas encore été analysées. Nous présentons ici une prolongation de cette étude de cohortes pour la seconde et la troisième vague de COVID-19. Méthodologie: Notre analyse porte sur des adultes ontariens ayant obtenu un résultat positif à un test de COVID-19 par réaction en chaîne de la polymérase entre le 1er janvier 2020 et le 30 juin 2021. Un algorithme validé pour l'analyse des noms de famille a été utilisé pour isoler les sujets de descendance chinoise ou sud-asiatique, et leur taux de mortalité de même que les complications cardiaques et neurologiques ont été comparés à ceux de la population générale à l'aide de modèles de régression logistique multivariée. Résultats: En comparaison de la population générale (n = 439 977), les personnes de descendance chinoise (n = 15 208) se sont révélées plus âgées (âge moyen de 44,2 ans contre 40,6 ans, P < 0,001), tandis que les personnes de descendance sud-asiatique (n = 46 333) étaient plus jeunes (39,2 ans, P < 0,001). Dans la population de descendance chinoise, le taux de mortalité après 30 jours était plus élevé (rapport de cotes [RC] de 1,44; intervalle de confiance [IC] à 95 % de 1,28 à 1,61), et davantage d'hospitalisations ou de consultations aux urgences sont survenues (RC de 1,14; IC à 95 % de 1,09 à 1,28). L'incidence de complications cardiaques (RC de 1,03; IC à 95 % de 0,87 à 1,12) et de complications neurologiques (RC de 1,23; IC à 95 % de 0,96 à 1,58) avait également tendance à être plus élevée. Chez les personnes de descendance sud-asiatique, le taux de mortalité après 30 jours était plus faible (RC de 0,88; IC à 95 % de 0,78 à 0,98), mais l'incidence d'hospitalisations ou de consultations aux urgences était plus élevée (RC de 1,17; IC à 95 % de 1,14 à 1,20). Elles présentaient également une tendance vers une plus faible incidence de complications cardiaques (RC de 0,76; IC à 95 % de 0,67 à 0,87) et de complications neurologiques (RC de 0,89; IC à 95 % de 0,73 à 1,09). Des différences significatives ont également été observées pour ces paramètres entre les vagues 1, 2 et 3 de la maladie, et le taux de mortalité était plus élevé pour tous les groupes des vagues 2 et 3. Conclusions: L'origine ethnique demeure un déterminant important de la mortalité, des issues cliniques cardiaques et neurologiques ainsi que de l'utilisation des ressources en santé chez les patients atteints de la COVID-19. D'autres études sont toutefois nécessaires pour mieux comprendre les facteurs qui expliquent ces différences.

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.

The association between anticoagulation and adverse outcomes after a positive SARS-CoV-2 test among older outpatients: A population-based cohort study.

INTRODUCTION: Anticoagulation may improve outcomes in patients with COVID-19 when started early in the course of illness. MATERIALS AND METHODS: This was a population-based cohort study using linked administrative datasets of outpatients aged ≥65 years old testing positive for SARS-CoV-2 between January 1 and December 31, 2020 in Ontario, Canada. The key exposure was anticoagulation with warfarin or direct oral anticoagulants before COVID-19 diagnosis. We calculated propensity scores and used matching weights (MWs) to reduce baseline differences between anticoagulated and non-anticoagulated patients. The primary outcome was a composite of death or hospitalization within 60 days of a positive SARS-CoV-2 test. We used the Kaplan-Meier method and cumulative incidence functions to estimate risk of the primary and component outcomes at 60 days. RESULTS: We studied 23,159 outpatients (mean age 78.5 years; 13,474 [58.2%] female), among whom 3200 (13.8%) deaths and 3183 (13.7%) hospitalizations occurred within 60 days of the SARS-CoV-2 test. After application of MWs, the 60-day risk of death or hospitalization was 29.2% (95% CI 27.4%-31.2%) for anticoagulated individuals and 32.1% (95% CI 30.7%-33.5%) without anticoagulation (absolute risk difference [ARD], -2.9%; p = 0.005). Anticoagulation was also associated with a lower risk of death: 18.6% (95% CI 17.0%-20.2%) with anticoagulation and 20.9% (95% CI 19.7%-22.2%) in non-anticoagulated patients (ARD -2.3%; p = 0.005). CONCLUSIONS: Among outpatients aged ≥65 years, oral anticoagulation at the time of a positive SARS-CoV-2 test was associated with a lower risk of a composite of death or hospitalization within 60 days.

Statins and SARS-CoV-2 Infection: Results of a Population-Based Prospective Cohort Study of 469 749 Adults From 2 Canadian Provinces.

Background Small observational studies have suggested that statin users have a lower risk of dying with COVID-19. We tested this hypothesis in a large, population-based cohort of adults in 2 of Canada's most populous provinces: Ontario and Alberta. Methods and Results We examined reverse transcriptase-polymerase chain reaction swab positivity rates for SARS-CoV-2 in adults using statins compared with nonusers. In patients with SARS-CoV-2 infection, we compared 30-day risk of all-cause emergency department visit, hospitalization, intensive care unit admission, or death in statin users versus nonusers, adjusting for baseline differences in demographics, clinical comorbidities, and prior health care use, as well as propensity for statin use. Between January and June 2020, 2.4% of 226 142 tested individuals aged 18 to 65 years, 2.7% of 88 387 people aged 66 to 75 years, and 4.1% of 154 950 people older than 75 years had a positive reverse transcriptase-polymerase chain reaction swab for SARS-CoV-2. Compared with 353 878 nonusers, the 115 871 statin users were more likely to test positive for SARS-CoV-2 (3.6% versus 2.8%, P<0.001), but this difference was not significant after adjustment for baseline differences and propensity for statin use in each age stratum (adjusted odds ratio 1.00 [95% CI, 0.88-1.14], 1.00 [0.91-1.09], and 1.06 [0.82-1.38], respectively). In individuals younger than 75 years with SARS-CoV-2 infection, statin users were more likely to visit an emergency department, be hospitalized, be admitted to the intensive care unit, or to die of any cause within 30 days of their positive swab result than nonusers, but none of these associations were significant after multivariable adjustment. In individuals older than 75 years with SARS-CoV-2, statin users were more likely to visit an emergency department (28.2% versus 17.9%, adjusted odds ratio 1.41 [1.23-1.61]) or be hospitalized (32.7% versus 21.9%, adjusted odds ratio 1.19 [1.05-1.36]), but were less likely to die (26.9% versus 31.3%, adjusted odds ratio 0.76 [0.67-0.86]) of any cause within 30 days of their positive swab result than nonusers. Conclusions Compared with statin nonusers, patients taking statins exhibit the same risk of testing positive for SARS-CoV-2 and those younger than 75 years exhibit similar outcomes within 30 days of a positive test. Patients older than 75 years with a positive SARS-CoV-2 test and who were taking statins had more emergency department visits and hospitalizations, but exhibited lower 30-day all-cause mortality risk.

The Impact of the COVID-19 Pandemic on Cardiac Procedure Wait List Mortality in Ontario, Canada.

BACKGROUND: The novel SARS-CoV-2 (COVID-19) pandemic has dramatically altered the delivery of healthcare services, resulting in significant referral pattern changes, delayed presentations, and procedural delays. Our objective was to determine the effect of the COVID-19 pandemic on all-cause mortality in patients awaiting commonly performed cardiac procedures. METHODS: Clinical and administrative data sets were linked to identify all adults referred for: (1) percutaneous coronary intervention; (2) coronary artery bypass grafting; (3) valve surgery; and (4) transcatheter aortic valve implantation, from January 2014 to September 2020 in Ontario, Canada. Piece-wise regression models were used to determine the effect of the COVID-19 pandemic on referrals and procedural volume. Multivariable Cox proportional hazards models were used to determine the effect of the pandemic on waitlist mortality for the 4 procedures. RESULTS: We included 584,341 patients who were first-time referrals for 1 of the 4 procedures, of whom 37,718 (6.4%) were referred during the pandemic. The pandemic period was associated with a significant decline in the number of referrals and procedures completed compared with the prepandemic period. Referral during the pandemic period was a significant predictor for increased all-cause mortality for the percutaneous coronary intervention (hazard ratio, 1.83; 95% confidence interval, 1.47-2.27) and coronary artery bypass grafting (hazard ratio, 1.96; 95% confidence interval, 1.28-3.01), but not for surgical valve or transcatheter aortic valve implantation referrals. Procedural wait times were shorter during the pandemic period compared with the prepandemic period. CONCLUSIONS: There was a significant decrease in referrals and procedures completed for cardiac procedures during the pandemic period. Referral during the pandemic was associated with increased all-cause mortality while awaiting coronary revascularization.

Predictors of mortality among long-term care residents with SARS-CoV-2 infection.

BACKGROUND: While individuals living in long-term care (LTC) homes have experienced adverse outcomes of SARS-CoV-2 infection, few studies have examined a broad range of predictors of 30-day mortality in this population. METHODS: We studied residents living in LTC homes in Ontario, Canada, who underwent PCR testing for SARS-CoV-2 infection from January 1 to August 31, 2020, and examined predictors of all-cause death within 30 days after a positive test for SARS-CoV-2. We examined a broad range of risk factor categories including demographics, comorbidities, functional status, laboratory tests, and characteristics of the LTC facility and surrounding community were examined. In total, 304 potential predictors were evaluated for their association with mortality using machine learning (Random Forest). RESULTS: A total of 64,733 residents of LTC, median age 86 (78, 91) years (31.8% men), underwent SARS-CoV-2 testing, of whom 5029 (7.8%) tested positive. Thirty-day mortality rates were 28.7% (1442 deaths) after a positive test. Of 59,702 residents who tested negative, 2652 (4.4%) died within 30 days of testing. Predictors of mortality after SARS-CoV-2 infection included age, functional status (e.g., activity of daily living score and pressure ulcer risk), male sex, undernutrition, dehydration risk, prior hospital contacts for respiratory illness, and duration of comorbidities (e.g., heart failure, COPD). Lower GFR, hemoglobin concentration, lymphocyte count, and serum albumin were associated with higher mortality. After combining all covariates to generate a risk index, mortality rate in the highest risk quartile was 48.3% compared with 7% in the first quartile (odds ratio 12.42, 95%CI: 6.67, 22.80, p < 0.001). Deaths continued to increase rapidly for 15 days after the positive test. CONCLUSIONS: LTC residents, particularly those with reduced functional status, comorbidities, and abnormalities on routine laboratory tests, are at high risk for mortality after SARS-CoV-2 infection. Recognizing high-risk residents in LTC may enhance institution of appropriate preventative measures.

COVID-19 and its Cardiac and Neurological Complications among Ontario Visible Minorities.

BACKGROUND: Due to lack of data on the epidemiology, cardiac, and neurological complications among Ontario visible minorities (Chinese and South Asians) affected by coronavirus disease (COVID-19), this population-based retrospective study was undertaken to study them systematically. METHODS: From January 1, 2020 to September 30, 2020 using the last name algorithm to identify Ontario Chinese and South Asians who were tested positive by PCR for COVID-19, their demographics, cardiac, and neurological complications including hospitalization and emergency visit rates were analyzed compared to the general population. RESULTS: Chinese (N = 1,186) with COVID-19 were found to be older (mean age 50.7 years) compared to the general population (N = 42,547) (mean age 47.6 years) (p < 0.001), while South Asians (N = 3,459) were younger (age of 42.1 years) (p < 0.001). The 30-day crude rate for cardiac complications among Chinese was 169/10,000 (p = 0.069), while for South Asians, it was 64/10,000 (p = 0.008) and, for the general population, it was 112/10,000. For neurological complications, the 30-day crude rate for Chinese was 160/10,000 (p < 0.001); South Asians was 40/10,000 (p = 0.526), and general population was 48/10,000. The 30-day all-cause mortality rate was significantly higher for Chinese at 8.1% vs 5.0% for the general population (p < 0.001), while it was lower in South Asians at 2.1% (p < 0.001). CONCLUSIONS: Chinese and South Asians in Ontario affected by COVID-19 during the first wave of the pandemic were found to have a significant difference in their demographics, cardiac, and neurological outcomes.

Rate of COVID-19 Infection in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The incidence of coronavirus disease 2019 (COVID-19) in patients with ST-segment elevation myocardial infarction (STEMI) has not been fully described. METHODS: All patients with STEMI undergoing primary percutaneous coronary intervention (PCI) in Ontario, Canada between March 1 and September 30, 2020 were included. Rates of positive COVID-19 tests from January 1, 2020 to the date of STEMI presentation were ascertained. For comparison, COVID-19 results were also evaluated in the adult Ontario population between January 1, 2020 and September 30, 2020, using provincial laboratory testing data. RESULTS: There were 3606 unique patients presenting with STEMI and receiving PCI in Ontario, Canada during the study period. Sixteen patients (0.44%) tested positive for COVID-19. The background infection rate among all 12,448,541 Ontario residents was similar, at 0.34%. CONCLUSIONS: The results of this population-based analysis suggest that proceeding with primary PCI with appropriate infection control practices is reasonable when community infection rates are low.

CONTEXTE: L'incidence de la maladie à coronavirus 2019 (COVID-19) chez les patients présentant un infarctus du myocarde avec élévation du segment ST (STEMI) n'a pas été entièrement décrite. MÉTHODOLOGIE: Tous les patients atteints de STEMI ayant subi une intervention coronarienne percutanée (ICP) primaire en Ontario (Canada) entre le 1er mars et le 30 septembre 2020 ont été inclus. Les taux de tests positifs à la COVID entre le 1er janvier 2020 et le moment de la présentation du STEMI ont été vérifiés. Aux fins de comparaison, les résultats des tests de dépistage de la COVID-19 ont également été évalués au sein de la population adulte de l'Ontario entre le 1er janvier 2020 et le 30 septembre 2020 au moyen des données des laboratoires provinciaux. RÉSULTATS: Pendant la période d'étude, 3 606 patients présentant un STEMI et ayant subi une ICP en Ontario (Canada) ont été recensés. Seize patients (0,44 %) ont reçu un résultat positif au test de dépistage de la COVID-19. Le taux d'infection parmi les 12 448 541 résidents de l'Ontario était similaire, soit 0,34 %. CONCLUSIONS: Les résultats de cette analyse populationnelle portent à penser qu'il est raisonnable de procéder à une ICP primaire avec des mesures appropriées de contrôle des infections lorsque les taux d'infection dans la collectivité sont faibles.

Early Observations During the COVID-19 Pandemic in Cardiac Catheterization Procedures for ST-Elevation Myocardial Infarction Across Ontario.

BACKGROUND: In response to the COVID-19 pandemic, Ontario issued a declaration of emergency, implementing public health interventions on March 16, 2020. METHODS: We compared cardiac catheterization procedures for ST-elevation myocardial infarction (STEMI) between January 1 and May 10, 2020 to the same time frame in 2019. RESULTS: From March 16 to May 10, 2020, after implementation of provincial directives, STEMI cases significantly decreased by up to 25%. The proportion of patients who achieved guideline targets for first medical contact balloon for primary percutaneous coronary intervention (PCI) decreased substantially to 28% (median, 101 minutes) for patients who presented directly to a PCI site and to 37% (median, 149 minutes) for patients transferred from a non-PCI site, compared with 2019. CONCLUSIONS: STEMI cases across Ontario have been substantially affected during the COVID-19 pandemic.

INTRODUCTION: En réponse à la pandémie de COVID-19, l'Ontario a déclaré l'état d'urgence et mis en place des interventions de santé publique le 16 mars 2020. MÉTHODES: Nous avons comparé les procédures de cathétérisme cardiaque lors d'infarctus du myocarde avec sus-décalage du segment ST (STEMI) du 1er janvier au 10 mai 2020 à la même période en 2019. RÉSULTATS: Du 16 mars au 10 mai 2020, après la mise en place des directives provinciales, les cas de STEMI ont connu une diminution significative pouvant atteindre jusqu'à 25 %. La proportion de patients qui ont atteint les objectifs prévus aux lignes directrices entre le premier contact médical et le ballonnet de l'intervention coronarienne percutanée (IPC) a connu une diminution considérable de 28 % (médiane, 101 minutes) pour ceux qui se présentaient directement dans un site d'IPC et de 37 % (médiane, 149 minutes) pour ceux qui étaient dirigés vers un site non-ICP, et ce, en comparaison à 2019. CONCLUSIONS: La pandémie de COVID-19 a considérablement nui aux cas de STEMI de l'Ontario.