Comparison of influenza and COVID-19 hospitalizations in British Columbia, Canada: a population-based study

ObjectiveTo compare the population rate of COVID-19 and influenza hospitalizations by age, COVID-19 vaccine status and pandemic phase. DesignObservational retrospective study SettingResidents of British Columbia (population 5.3 million), Canada ParticipantsHospitalized patients due to COVID-19 or historical influenza Main outcome measuresThis population based study in a setting with universal healthcare coverage, used COVID-19 case and hospital data for COVID-19 and influenza. Admissions were selected from March 2020 to February 2021 for the annual cohort and the first 8 weeks of 2022 for the peak cohort of COVID-19 (Omicron era). Influenza annual and peak cohorts were from three years with varying severity: 2009/10, 2015/16, and 2016/17. We estimated hospitalization rates per 100,000 population by age group. ResultsSimilar to COVID-19 with median age 66 (Q1-Q3 44-80), influenza 2016/17 mostly affected older adults, with median age 78 (64-87). COVID-19 and influenza 2016/17 hospitalization rate by age group were "J" shaped. The rates for mostly unvaccinated COVID-19 patients in 2020/21 in the context of public health restrictions were significantly higher than influenza among individuals 30 to 69 years of age, and comparable to a severe influenza year (2016/17) among 70+. In early 2022 (Omicron peak), rates primarily due to COVID-19 among vaccinated adults were comparable with influenza 2016/17 in all age groups while rates among unvaccinated COVID-19 patients were still higher than influenza among 18+. In the pediatric population, COVID-19 hospitalization rates were similar to or lower than influenza. ConclusionsOur paper highlighted the greater population-level impact of COVID-19 compared with influenza in terms of adult hospitalizations, especially among those unvaccinated. However, influenza had greater impact than COVID-19 among <18 regardless of vaccine status or the circulating variant.

Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada

BackgroundThe Canadian COVID-19 immunization strategy deferred second doses and allowed mixed schedules. We compared two-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in two of Canadas larger provinces. MethodsTwo-dose VE against infections and hospitalizations due to SARS-CoV-2, including variants of concern, was assessed between May 30 and October 2, 2021 using test-negative designs separately conducted among community-dwelling adults [≥]18-years-old in British Columbia (BC) and Quebec, Canada. FindingsIn both provinces, two doses of homologous or heterologous SARS-CoV-2 vaccines were associated with [~]95% reduction in the risk of hospitalization. VE exceeded 90% against SARS-CoV-2 infection when at least one dose was an mRNA vaccine, but was lower at [~]70% when both doses were ChAdOx1. Estimates were similar by age group (including adults [≥]70-years-old) and for Delta-variant outcomes. VE was significantly higher against both infection and hospitalization with longer 7-8-week vs. manufacturer-specified 3-4-week interval between doses. Two-dose mRNA VE was maintained against hospitalization for the 5-7-month monitoring period and while showing some decline against infection, remained [≥]80%. InterpretationTwo doses of mRNA and/or ChAdOx1 vaccines gave excellent protection against hospitalization, with no sign of decline by 5-7 months post-vaccination. A 7-8-week interval between doses improved VE and may be optimal in most circumstances. Findings indicate prolonged two-dose protection and support the use of mixed schedules and longer intervals between doses, with global health, equity and access implications in the context of recent third-dose proposals.

Comparative single-dose mRNA and ChAdOx1 vaccine effectiveness against SARS-CoV-2, including early variants of concern: a test-negative design, British Columbia, Canada

IntroductionIn randomized controlled trials, single-dose efficacy against SARS-CoV-2 illness exceeded 90% for mRNA vaccines (BNT162b2 and mRNA-1273), and 75% for ChAdOx1. In British Columbia (BC), Canada second doses were deferred up to 16 weeks and ChAdOx1 was only initially recommended for adults 55 years of age and older. We compared single-dose vaccine effectiveness (VE) during the spring 2021 wave in BC when Alpha and Gamma variants of concern (VOC) predominated. MethodsVE was estimated against infection and hospitalization by test-negative design: cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Adults 50-69 years old with specimen collection between April 4 and May 22 (weeks 14-20) were included. Variant-specific VE was estimated between weeks 17-20 when genetic characterization of all case viruses was performed, primarily through whole genome sequencing. ResultsVE analyses included 7,116 (10%) cases and 60,958 controls. Three-quarters of vaccinated participants received mRNA vaccine (60% BNT162b2, 15% mRNA-1273) and 25% received ChAdOx1. Half of genetically characterized viruses were Alpha, with 38% Gamma, 4% Delta and 8% non-VOCs. Single-dose VE against any infection was 75% (95%CI: 72-78) for BNT162b2, 82% (95%CI: 76-87) for mRNA-1273 and 61% (95%CI: 54-66) for ChAdOx1. VE against hospitalization was 83% (95%CI: 76-89), 85% (95%CI: 63-94) and 96% (95%CI: 86-99), respectively. VE against Alpha vs. Gamma infections did not differ among mRNA (78%;95%CI: 73-82 and 80%;95%CI: 74-85) or ChAdOx1 (66%;95%CI: 57-74 and 60%;95%CI: 48-69) recipients. ConclusionsA single dose of mRNA vaccine reduced the SARS-CoV-2 infection risk by at least 75%, including infections due to early VOC. Although effectiveness of a single dose of ChAdOx1 was lower at 60% against infection, just one dose of any vaccine reduced the hospitalization risk by more than 80%. In the context of constrained vaccine supplies, these findings have implications for global vaccine deployment to reduce the overall burden of infections and hospitalizations due to SARS-CoV-2.

Single-dose mRNA vaccine effectiveness against SARS-CoV-2, including P.1 and B.1.1.7 variants: a test-negative design in adults 70 years and older in British Columbia, Canada

IntroductionRandomized-controlled trials of mRNA vaccine protection against SARS-CoV-2 included relatively few elderly participants. We assess singe-dose mRNA vaccine effectiveness (VE) in adults [≥]70-years-old in British Columbia (BC), Canada where the second dose was deferred by up to 16 weeks and where a spring 2021 wave uniquely included co-dominant circulation of B.1.1.7 and P.1 variants of concern (VOC). MethodsAnalyses included community-dwelling adults [≥]70-years-old with specimen collection between April 4 (epidemiological week 14) and May 1 (week 17). Adjusted VE was estimated by test-negative design through provincial laboratory and immunization data linkage. Cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Vaccine status was defined by receipt of a single-dose [≥]21 days before specimen collection, but a range of intervals was assessed. In variant-specific analyses, test-positive cases were restricted to those genetically-characterized as B.1.1.7, P.1 or non-VOC. ResultsVE analyses included 16,993 specimens: 1,226 (7.2%) test-positive cases and 15,767 test-negative controls. Of 1,131 (92%) viruses genetically categorized, 509 (45%), 314 (28%) and 276 (24%) were B.1.1.7, P.1 and non-VOC lineages, respectively. VE was negligible at 14% (95% CI 0-26) during the period 0-13 days post-vaccination but increased from 43% (95% CI 30-53) at 14-20 days to 75% (95% CI 63-83) at 35-41 days post-vaccination. VE at [≥]21 days was 65% (95% CI 58-71) overall: 72% (95% CI 58-81), 67% (95% CI 57-75) and 61% (95% CI 45-72) for non-VOC, B.1.1.7 and P.1, respectively. ConclusionsA single dose of mRNA vaccine reduced the risk of SARS-CoV-2 in adults [≥]70-years-old by about two-thirds, with protection only minimally reduced against B.1.1.7 and P.1 variants. Substantial single-dose protection in older adults reinforces the option to defer the second dose when vaccine supply is scarce and broader first-dose coverage is needed.

Optimizing SARS-CoV-2 Variant of Concern Screening: Experience from British Columbia, Canada, Early 2021

Comprehensive and timely testing is required for SARS-CoV-2 variant of concern (VoC) screening. Whole genome sequencing (WGS) provides the broadest means to detect circulating VoCs, but requires longer turnaround time than targeted molecular testing by quantitative polymerase chain reaction (qPCR). We demonstrated the feasibility of a combined testing approach for VoC prevalence assessment in British Columbia, and showed high concordance between qPCR testing and WGS. This directly informed wider VoC screening strategy implementation, and public health efforts.

When physical activity meets the physical environment: precision health insights from the intersection

BACKGROUND@#The physical environment can facilitate or hinder physical activity. A challenge in promoting physical activity is ensuring that the physical environment is supportive and that these supports are appropriately tailored to the individual or group in question. Ideally, aspects of the environment that impact physical activity would be enhanced, but environmental changes take time, and identifying ways to provide more precision to physical activity recommendations might be helpful for specific individuals or groups. Therefore, moving beyond a "one size fits all" to a precision-based approach is critical.@*MAIN BODY@#To this end, we considered 4 critical aspects of the physical environment that influence physical activity (walkability, green space, traffic-related air pollution, and heat) and how these aspects could enhance our ability to precisely guide physical activity. Strategies to increase physical activity could include optimizing design of the built environment or mitigating of some of the environmental impediments to activity through personalized or population-wide interventions.@*CONCLUSIONS@#Although at present non-personalized approaches may be more widespread than those tailored to one person's physical environment, targeting intrinsic personal elements (e.g., medical conditions, sex, age, socioeconomic status) has interesting potential to enhance the likelihood and ability of individuals to participate in physical activity.

The Contrasting Role of Nasopharyngeal Angiotensin Converting Enzyme 2 (ACE2) Expression in SARS-CoV-2 Infection: A Cross-Sectional Study of People Tested for COVID-19 in British Columbia

BackgroundAngiotensin converting enzyme 2 (ACE2) serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngeal ACE2 expression in people tested for COVID-19 and the relationship between ACE2 expression and SARS-CoV-2 viral RNA load, while adjusting for expression of the complementary protease, Transmembrane serine protease 2 (TMPRSS2), soluble ACE2, age, and biological sex. MethodsA cross-sectional study of n=424 participants aged 1-104 years referred for COVID-19 testing was performed in British Columbia, Canada. Participants who tested negative or positive for COVID-19 were matched by age and biological sex. Viral and host gene expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngeal ACE2 expression in SARS-CoV-2 infection. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts. FindingsAnalysis shows no association between age and nasopharyngeal ACE2 expression in those who tested negative for COVID-19 (P=0{middle dot}092). Mean expression of transmembrane (P=1{middle dot}2e-4), soluble ACE2 (P<0{middle dot}0001) and TMPRSS2 (P<0{middle dot}0001) differed between COVID-19-negative and -positive groups. In bivariate analysis of COVID-19-positive participants, expression of transmembrane ACE2 positively correlated with SARS-CoV-2 RNA viral load (P<0{middle dot}0001), expression of soluble ACE2 negatively correlated (P<0{middle dot}0001), and no correlation was found with TMPRSS2 (P=0{middle dot}694). Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane ACE2 expression (B=0{middle dot}886, 95%CI:[0{middle dot}596 to 1{middle dot}18]), while expression of soluble ACE2 may protect against high viral RNA load in the upper respiratory tract (B= -0{middle dot}0990, 95%CI:[-0{middle dot}176 to -0{middle dot}0224]). InterpretationNasopharyngeal ACE2 expression plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transmembrane ACE2 positively correlates, while soluble ACE2 negatively correlates with viral RNA load after adjusting for age, biological sex and expression of TMPRSS2. FundingThis project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.