[Clinical Infectious Diseases, 17 August 2022]

Background: A major goal of coronavirus disease 2019 (COVID-19) vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of messenger RNA (mRNA) and ChAdOx1 COVID-19 vaccines against severe outcomes in 4 Canadian provinces between December 2020 and September 2021.

Methods: We conducted this multiprovincial, retrospective, test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random-effects models.

Results: We included 2 508 296 tested participants, with 31 776 COVID-19 hospitalizations and 5842 deaths. Vaccine effectiveness was 83% after a first dose and 98% after a second dose against both hospitalization and death (separately). Against severe outcomes, effectiveness was 87% (95% confidence interval [CI], 71%–94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95% CI, 96%–99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95% CI, 75%–94%) ≥56 days after a first dose, increasing to 97% (95% CI, 91%–99%) ≥56 days after a second dose. Lower 1-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules and against Alpha, Gamma, and Delta variants.

Conclusions: Two doses of mRNA or ChAdOx1 vaccine provide excellent protection against severe outcomes.

[PLoS ONE, 9 September 2022]

Importance: The measurement of laboratory biomarkers plays a critical role in managing patients with COVID-19. However, to date most systematic reviews examining the association between laboratory biomarkers and mortality in hospitalized patients early in the pandemic focused on small sets of biomarkers, did not account for multiple studies including patients within the same institutions during overlapping timeframes, and did not include a significant number of studies conducted in countries other than China.

Objective: To provide a comprehensive summary and an evidence map examining the relationship between a wide range of laboratory biomarkers and mortality among patients hospitalized with COVID-19 during the early phase of the pandemic in multiple countries.

Evidence review: MEDLINE, EMBASE, and Web of Science were searched from Dec 2019 to March 9, 2021. A total of 14,049 studies were identified and screened independently by two raters; data was extracted by a single rater and verified by a second. Quality was assessed using the Joanna Briggs Institute (JBI) Case Series Critical Appraisal tool. To allow comparison across biomarkers, standardized mean differences (SMD) were used to quantify the relationship between laboratory biomarkers and hospital mortality. Meta-regression was conducted to account for clustering within institutions and countries.

Results: Our systematic review included 94 case-series studies from 30 countries. Across all biomarkers, the largest and most precise SMDs were observed for cardiac (troponin (1.03 (95% CI 0.86 to 1.21)), and BNP/NT-proBNP (0.93 (0.52 to 1.34)), inflammatory (IL-6 (0.97 (0.67 to 1.28) and Neutrophil-to-lymphocyte ratio (0.94 (0.59 to 1.29)), and renal biomarkers (blood urea nitrogen (1.01 (0.79 to 1.23)) and estimated glomerular filtration rate (-0.96 (-1.42 to -0.50)). There was heterogeneity for most biomarkers across countries with studies conducted in China generally having larger effect sizes.

Conclusions and relevance: The results of this study provide an early pandemic summary of the relationship between biomarkers and mortality in hospitalized patients. We found our estimated ESs were generally attenuated compared to previous systematic reviews which predominantly included studies conducted in China. Despite using sophisticated methodology to examine studies across countries, heterogeneity in reporting of case-series studies early in the pandemic limits clinical interpretability.

[Canada Communicable Disease Report, 31 May 2023]

Background: National responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have been highly variable. We sought to explore the effectiveness of the Canadian pandemic response up to May 2022 relative to responses in four peer countries with similar political, economic and health systems, and with close historical and cultural ties to Canada.

Methods: We used reported age-specific mortality data to generate estimates of pandemic mortality standardized to the Canadian population. Age-specific case fatality, hospitalization, and intensive care admission probabilities for the Canadian province of Ontario were applied to estimated deaths, to calculate hospitalizations and intensive care admissions averted by the Canadian response. Health impacts were valued in both monetary terms, and in terms of lost quality-adjusted life years.

Results: We estimated that the Canadian pandemic response averted 94,492, 64,306 and 13,641 deaths relative to the responses of the United States, United Kingdom and France, respectively, and more than 480,000 hospitalizations relative to the United States. The United States pandemic response, if applied to Canada, would have resulted in more than $40 billion in economic losses due to healthcare expenditures and lost quality-adjusted life years. In contrast, an Australian pandemic response applied to Canada would have averted over 28,000 additional deaths and averted nearly $9 billion in costs.

Conclusion: Canada outperformed several peer countries that aimed for mitigation rather than elimination of SARS-CoV-2 in the first two years of the pandemic, with substantial numbers of lives saved and economic costs averted. However, a comparison with Australia demonstrated that an elimination focus would have saved Canada tens of thousands of lives as well as substantial economic costs.

[International Journal of Drug Policy, 17 April 2023]

Background: In Montreal (Canada), high hepatitis C virus (HCV) seroincidence (21 per 100 person-years in 2017) persists among people who have injected drugs (PWID) despite relatively high testing rates and coverage of needle and syringe programs (NSP) and opioid agonist therapy (OAT). We assessed the potential of interventions to achieve HCV elimination (80% incidence reduction and 65% reduction in HCV-related mortality between 2015 and 2030) in the context of COVID-19 disruptions among all PWID and PWID living with HIV.

Methods: Using a dynamic model of HCV-HIV co-transmission, we simulated increases in NSP (from 82% to 95%) and OAT (from 33% to 40%) coverage, HCV testing (every 6 months), or treatment rate (100 per 100 person-years) starting in 2022 among all PWID and PWID living with HIV. We also modeled treatment scale-up among active PWID only (i.e., people who report injecting in the past six months). We reduced intervention levels in 2020–2021 due to COVID-19-related disruptions. Outcomes included HCV incidence, prevalence, and mortality, and proportions of averted chronic HCV infections and deaths.

Results: COVID-19-related disruptions could have caused temporary rebounds in HCV transmission. Further increasing NSP/OAT or HCV testing had little impact on incidence. Scaling-up treatment among all PWID achieved incidence and mortality targets among all PWID and PWID living with HIV. Focusing treatment on active PWID could achieve elimination, yet fewer projected deaths were averted (36% versus 48%).

Conclusions: HCV treatment scale-up among all PWID will be required to eliminate HCV in high-incidence and prevalence settings. Achieving elimination by 2030 will entail concerted efforts to restore and enhance pre-pandemic levels of HCV prevention and care.

[Clinical Infectious Diseases, 28 October 2022]

Background: Social determinants of health (SDOH) have been associated with coronavirus disease 2019 (COVID-19) outcomes. We examined patterns in COVID-19–related mortality by SDOH and compared these patterns to those for non–COVID-19 mortality.

Methods: Residents of Ontario, Canada, aged ≥20 years were followed from 1 March 2020 to 2 March 2021. COVID-19–related death was defined as death within 30 days following or 7 days prior to a positive COVID-19 test. Area-level SDOH from the 2016 census included median household income; proportion with diploma or higher educational attainment; proportion essential workers, racially minoritized groups, recent immigrants, apartment buildings, and high-density housing; and average household size. We examined associations between SDOH and COVID-19–related mortality, and non-COVID-19 mortality using cause-specific hazard models.

Results: Of 11 810 255 individuals, we observed 3880 COVID-19–related deaths and 88 107 non–COVID-19 deaths. After accounting for demographics, baseline health, and other area-level SDOH, the following were associated with increased hazards of COVID-19–related death (hazard ratio [95% confidence interval]: 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 minoritized 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]). Areas with higher proportion racially minoritized 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 minoritized groups. Pandemic responses should include strategies to address disproportionate risks and inequitable coverage of preventive interventions associated with SDOH.

[The Lancet Regional Health, 28 December 2022]

Background: The fourth wave of COVID-19 pandemic peaked in the US at 160,000 daily cases, concentrated primarily in southern states. As the Delta variant has continued to spread, we evaluated the impact of accelerated vaccination on reducing hospitalization and deaths across northeastern and southern regions of the US census divisions.

Methods: We used an age-stratified agent-based model of COVID-19 to simulate outbreaks in all states within two U.S. regions. The model was calibrated using reported incidence in each state from October 1, 2020 to August 31, 2021, and parameterized with characteristics of the circulating SARS-CoV-2 variants and state-specific daily vaccination rate. We then projected the number of infections, hospitalizations, and deaths that would be averted between September 2021 and the end of March 2022 if the states increased their daily vaccination rate by 20 or 50% compared to maintaining the status quo pace observed during August 2021.

Findings: A 50% increase in daily vaccine doses administered to previously unvaccinated individuals is projected to prevent a total of 30,727 hospitalizations and 11,937 deaths in the two regions between September 2021 and the end of March 2022. Southern states were projected to have a higher weighted average number of hospitalizations averted (18.8) and lives saved (8.3) per 100,000 population, compared to the weighted average of hospitalizations (12.4) and deaths (2.7) averted in northeastern states. On a per capita basis, a 50% increase in daily vaccinations is expected to avert the most hospitalizations in Kentucky (56.7 hospitalizations per 100,000 averted with 95% CrI: 45.56 - 69.9) and prevent the most deaths in Mississippi, (22.1 deaths per 100,000 population prevented with 95% CrI: 18.0 - 26.9).

Interpretation: Accelerating progress to population-level immunity by raising the daily pace of vaccination would prevent substantial hospitalizations and deaths in the US, even in those states that have passed a Delta-driven peak in infections.

Citerank: (11) 679746Steini BrownProfessor and Dean of the Dalla Lana School of Public Health at the University of Toronto.10019D3ABAB, 679755Ashleigh TuiteAshleigh Tuite is an Assistant Professor in the Epidemiology Division at the Dalla Lana School of Public Health at the University of Toronto.10019D3ABAB, 679757Beate SanderCanada Research Chair in Economics of Infectious Diseases and Director, Health Modeling & Health Economics and Population Health Economics Research at THETA (Toronto Health Economics and Technology Assessment Collaborative).10019D3ABAB, 679777David FismanI am a Professor in the Division of Epidemiology at Division of Epidemiology, Dalla Lana School of Public Health at the University of Toronto. I am a Full Member of the School of Graduate Studies. I also have cross-appointments at the Institute of Health Policy, Management and Evaluation and the Department of Medicine, Faculty of Medicine. I serve as a Consultant in Infectious Diseases at the University Health Network.10019D3ABAB, 679802Isaac BogochClinician Investigator, Toronto General Hospital Research Institute (TGHRI)10019D3ABAB, 679893Kumar MurtyProfessor Kumar Murty is in the Department of Mathematics at the University of Toronto. His research fields are Analytic Number Theory, Algebraic Number Theory, Arithmetic Algebraic Geometry and Information Security. He is the founder of the GANITA lab, co-founder of Prata Technologies and PerfectCloud. His interest in mathematics ranges from the pure study of the subject to its applications in data and information security.10019D3ABAB, 685230Doug ManuelDr. Manuel is a Medical Doctor with a Masters in Epidemiology and Royal College specialization in Public Health and Preventive Medicine. He is a Senior Scientist in the Clinical Epidemiology Program at Ottawa Hospital Research Institute, and a Professor in the Departments of Family Medicine and Epidemiology and Community Medicine.10019D3ABAB, 685420Hospitals16289D5D4, 701020CANMOD – PublicationsPublications by CANMOD Members144B5ACA0, 701037MfPH – Publications144B5ACA0, 704045Covid-19859FDEF6

[Science Briefs of the Ontario COVID-19 Science Advisory Table, 29 March 2021]

Background: As of March 28, 2021 new variants of concern (VOCs) account for 67% of all Ontario SARS-CoV-2 infections. The B.1.1.7 variant originally detected in Kent, United Kingdom accounts for more than 90% of all VOCs in Ontario, with emerging evidence that it is both more transmissible and virulent.

Questions: What are the risks of COVID-19 hospitalization, ICU admission and death caused by VOCs as compared with the early variants of SARS-CoV-2?

What is the early impact of new VOCs on Ontario’s healthcare system?

Findings: A retrospective cohort study of 26,314 people in Ontario testing positive for SARS-CoV-2 between February 7 and March 11, 2021, showed that 9,395 people (35.7%) infected with VOCs had a 62% relative increase in COVID-19 hospitalizations (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.41 to 1.87), a 114% relative increase in ICU admissions (OR 2.14, 95% CI 1.52 to 3.02), and a 40% relative increase in COVID-19 deaths (OR 1.40, 95% CI 1.01 to 1.94), after adjusting for age, sex and comorbidities.

A meta-analysis including the Ontario cohort study and additional cohort studies in the United Kingdom and Denmark showed that people infected with VOCs had a 63% higher risk of hospitalization (RR 1.63, 95% CI 1.44 to 1.83), a doubling of the risk of ICU admission (RR 2.03, 95% CI 1.69 to 2.45), and a 56% higher risk of all-cause death (RR 1.56, 95% CI 1.30 to 1.87). Estimates observed in different studies and regions were completely consistent, and the B.1.1.7 variant was dominant in all three jurisdictions over the study periods.

The number of people hospitalized with COVID-19 on March 28, 2021, is 21% higher than at the start of the province-wide lockdown during the second wave on December 26, 2020, while ICU occupancy is 28% higher.

Between December 14 to 20, 2020, there were 149 new admissions to ICU; people aged 59 years and younger accounted for 30% of admissions. Between March 15, 2021 and March 21, 2021, there were 157 new admissions to ICU; people aged 59 years and younger accounted for 46% of admissions.

Interpretation: The new VOCs will result in a considerably higher burden to Ontario’s health care system during the third wave compared to the impact of early SARS-CoV-2 variants during Ontario’s second wave.

Since the start of the third wave on March 1, 2021, the number of new cases of SARS-CoV-2 infection, and the COVID-19 hospital and ICU occupancies have surpassed prior thresholds at the start of the province-wide lockdown on December 26, 2020.