Association of COVID-19 Infection With Incident Diabetes.

Importance: SARS-CoV-2 infection may lead to acute and chronic sequelae. Emerging evidence suggests a higher risk of diabetes after infection, but population-based evidence is still sparse. Objective: To evaluate the association between COVID-19 infection, including severity of infection, and risk of diabetes. Design, Setting, and Participants: This population-based cohort study was conducted in British Columbia, Canada, from January 1, 2020, to December 31, 2021, using the British Columbia COVID-19 Cohort, a surveillance platform that integrates COVID-19 data with population-based registries and administrative data sets. Individuals tested for SARS-CoV-2 by real-time reverse transcription-polymerase chain reaction (RT-PCR) were included. Those who tested positive for SARS-CoV-2 (ie, those who were exposed) were matched on sex, age, and collection date of RT-PCR test at a 1:4 ratio to those who tested negative (ie, those who were unexposed). Analysis was conducted January 14, 2022, to January 19, 2023. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was incident diabetes (insulin dependent or not insulin dependent) identified more than 30 days after the specimen collection date for the SARS-CoV-2 test with a validated algorithm based on medical visits, hospitalization records, chronic disease registry, and prescription drugs for diabetes management. Multivariable Cox proportional hazard modeling was performed to evaluate the association between SARS-CoV-2 infection and diabetes risk. Stratified analyses were performed to assess the interaction of SARS-CoV-2 infection with diabetes risk by sex, age, and vaccination status. Results: Among 629 935 individuals (median [IQR] age, 32 [25.0-42.0] years; 322 565 females [51.2%]) tested for SARS-CoV-2 in the analytic sample, 125 987 individuals were exposed and 503 948 individuals were unexposed. During the median (IQR) follow-up of 257 (102-356) days, events of incident diabetes were observed among 608 individuals who were exposed (0.5%) and 1864 individuals who were not exposed (0.4%). The incident diabetes rate per 100 000 person-years was significantly higher in the exposed vs nonexposed group (672.2 incidents; 95% CI, 618.7-725.6 incidents vs 508.7 incidents; 95% CI, 485.6-531.8 incidents; P < .001). The risk of incident diabetes was also higher in the exposed group (hazard ratio [HR], 1.17; 95% CI, 1.06-1.28) and among males (adjusted HR, 1.22; 95% CI, 1.06-1.40). The risk of diabetes was higher among people with severe disease vs those without COVID-19, including individuals admitted to the intensive care unit (HR, 3.29; 95% CI, 1.98-5.48) or hospital (HR, 2.42; 95% CI, 1.87-3.15). The fraction of incident diabetes cases attributable to SARS-CoV-2 infection was 3.41% (95% CI, 1.20%-5.61%) overall and 4.75% (95% CI, 1.30%-8.20%) among males. Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with a higher risk of diabetes and may have contributed to a 3% to 5% excess burden of diabetes at a population level.

A population-based assessment of myocarditis after messenger RNA COVID-19 booster vaccination among adult recipients.

OBJECTIVES: We aimed to estimate the rate of myocarditis after the messenger RNA (mRNA) COVID-19 booster vaccination by vaccine type, age, and sex. METHODS: We used data from the British Columbia COVID-19 Cohort, a population-based cohort surveillance platform. The exposure was a booster dose of an mRNA vaccine. The outcome was diagnosis of myocarditis during hospitalization or an emergency department visit within 7-21 days of booster vaccination. RESULTS: The overall rate of myocarditis was lower for the booster dose (6.41, 95% confidence interval [CI]: 3.50-10.75) than the second dose (17.97, 95% CI: 13.78-23.04); (Rate ratiobooster vs dose-2 = 0.34, 95% CI: 0.17-0.61). This difference was more apparent for the mRNA-1273 vaccine type. After the second dose, the myocarditis rate in males was significantly lower for BNT162b2 than mRNA-1273 overall and among those aged 18-39 years. In contrast, after the booster dose, no significant differences between myocarditis and vaccine type was observed overall or within the specific age groups among males or females. CONCLUSION: Myocarditis after mRNA COVID-19 vaccines is a rare event. A lower absolute risk of myocarditis was observed after a booster dose of mRNA vaccine than the primary series second dose.

Risk factors for COVID-19 hospitalization after COVID-19 vaccination: a population-based cohort study in Canada.

OBJECTIVES: With the uptake of COVID-19 vaccines, there is a need for population-based studies to assess risk factors for COVID-19-related hospitalization after vaccination and how they differ from unvaccinated individuals. METHODS: We used data from the British Columbia COVID-19 Cohort, a population-based cohort that includes all individuals (aged ≥18 years) who tested positive for SARS-CoV-2 by real-time reverse transcription-polymerase chain reaction from January 1, 2021 (after the start of vaccination program) to December 31, 2021. We used multivariable logistic regression models to assess COVID-19-related hospitalization risk by vaccination status and age group among confirmed COVID-19 cases. RESULTS: Of the 162,509 COVID-19 cases included in the analysis, 8,546 (5.3%) required hospitalization. Among vaccinated individuals, an increased odds of hospitalization with increasing age was observed for older age groups, namely those aged 50-59 years (odds ratio [OR] = 2.95, 95% confidence interval [CI]: 2.01-4.33), 60-69 years (OR = 4.82, 95% CI: 3.29, 7.07), 70-79 years (OR = 11.92, 95% CI: 8.02, 17.71), and ≥80 years (OR = 24.25, 95% CI: 16.02, 36.71). However, among unvaccinated individuals, there was a graded increase in odds of hospitalization with increasing age, starting at age group 30-39 years (OR = 2.14, 95% CI: 1.90, 2.41) to ≥80 years (OR = 41.95, 95% CI: 35.43, 49.67). Also, comparing all the age groups to the youngest, the observed magnitude of association was much higher among unvaccinated individuals than vaccinated ones. CONCLUSION: Alongside a number of comorbidities, our findings showed a strong association between age and COVID-19-related hospitalization, regardless of vaccination status. However, age-related hospitalization risk was reduced two-fold by vaccination, highlighting the need for vaccination in reducing the risk of severe disease and subsequent COVID-19-related hospitalization across all population groups.

Clinical severity of Omicron SARS-CoV-2 variant relative to Delta in British Columbia, Canada: A retrospective analysis of whole genome sequenced cases.

BACKGROUND: In late 2021, the Omicron SARS-CoV-2 variant emerged and rapidly replaced Delta as the dominant variant globally. The increased transmissibility of the variant led to surges in case rates as well as increases in hospitalizations, however, the true severity of the variant remained unclear. We aimed to provide robust estimates of Omicron severity relative to Delta. METHODS: This study was conducted using a retrospective cohort design with data from the British Columbia COVID-19 Cohort - a large provincial surveillance platform with linkage to administrative datasets. To capture the time of co-circulation with Omicron and Delta, December 2021 was chosen as the study period. We included individuals diagnosed with Omicron or Delta infection, as determined by whole genome sequencing (WGS). To assess the severity (hospitalization, ICU admission, length of stay), we conducted adjusted Cox proportional hazard models, weighted by inverse probability of treatment weights (IPTW), accounting for age, sex, underlying comorbidities, vaccination, sociodemographic status, and geographical variation. RESULTS: The cohort was composed of 13,128 individuals (7,729 Omicron and 5,399 Delta). There were 419 COVID-19 hospitalizations, with 118 (22%) among people diagnosed with Omicron (crude rate = 1.5% Omicron, 5.6% Delta). In multivariable IPTW analysis, Omicron was associated with a 50% lower risk of hospitalization compared to Delta (aHR = 0.50; 95%CI = 0·43-0.59), a 73% lower risk of ICU admission (aHR = 0.27; 95%CI = 0.19-0.38), and a 5 days shorter hospital stay on average (aß=-5.03; 95% CI=-8.01, -2.05). CONCLUSIONS: Our analysis supports findings from other studies demonstrating lower risk of severe outcomes in Omicron-infected individuals relative to Delta.

Effectiveness of COVID-19 Vaccines in People Living with HIV in British Columbia and comparisons with a matched HIV-Negative Cohort: A Test Negative Design.

BACKGROUND: We estimated the effectiveness of COVID-19 vaccines against laboratory-confirmed SARS-CoV-2 infection among people living with HIV (PLWH) and compared estimates with a matched HIV-negative cohort. METHOD: We used the British Columbia COVID-19 Cohort, a population-based data platform which integrates COVID-19 data on SARS-CoV-2 tests, laboratory-confirmed cases, and immunizations with provincial health services data. Vaccine effectiveness (VE) was estimated with a test-negative design using multivariable logistic regression. RESULTS: Adjusted VE against SARS-CoV-2 infection was 79.2% (52.5, 90.9%) 7-59 days after two doses, rising to 91.6% (75.2, 97.2%) between 60-89 days. VE was preserved four to six months following receipt of 2 doses after which slight waning was observed (72.7% [39.1, 87.8%]). In the matched cohort (n=375 043), VE peaked at 91.0% (90.5, 91.5%) 7-59 days after 2 doses and was sustained for up to four months after which evidence of waning was observed, dropping to 83.8% (82.9, 84.7%) between four to six months. CONCLUSION: Receipt of two COVID-19 vaccines doses was effective against SARS-CoV-2 infection among PLWH pre-Omicron. VE estimates appeared to peak later in PLWH compared to the matched HIV-negative cohort and the degree of waning was relatively quicker in PLWH; however, overall estimates were comparable in both populations.

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

INTRODUCTION: We compared the population rate of COVID-19 and influenza hospitalisations by age, COVID-19 vaccine status and pandemic phase, which was lacking in other studies. METHOD: We conducted a population-based study using hospital data from the province of British Columbia (population 5.3 million) in Canada with universal healthcare coverage. We created two cohorts of COVID-19 hospitalisations based on date of admission: annual cohort (March 2020 to February 2021) and peak cohort (Omicron era; first 10 weeks of 2022). For comparison, we created influenza annual and peak cohorts using three historical periods years to capture varying severity and circulating strains: 2009/2010, 2015/2016 and 2016/2017. We estimated hospitalisation rates per 100 000 population. RESULTS: COVID-19 and influenza hospitalisation rates by age group were 'J' shaped. The population rate of COVID-19 hospital admissions in the annual cohort (mostly unvaccinated; public health restrictions in place) was significantly higher than influenza among individuals aged 30-69 years, and comparable to the severe influenza year (2016/2017) among 70+. In the peak COVID-19 cohort (mostly vaccinated; few restrictions in place), the hospitalisation rate was comparable with influenza 2016/2017 in all age groups, although rates among the unvaccinated population were still higher than influenza among 18+. Among people aged 5-17 years, COVID-19 hospitalisation rates were lower than/comparable to influenza years in both cohorts. The COVID-19 hospitalisation rate among 0-4 years old, during Omicron, was higher than influenza 2015/2016 and 2016/2017 and lower than 2009/2010 pandemic. CONCLUSIONS: During first Omicron wave, COVID-19 hospitalisation rates were significantly higher than historical influenza hospitalisation rates for unvaccinated adults but were comparable to influenza for vaccinated adults. For children, in the context of high infection levels, hospitalisation rates for COVID-19 were lower than 2009/2010 H1N1 influenza and comparable (higher for 0-4) to non-pandemic years, regardless of the vaccine status.

Observed versus expected rates of myocarditis after SARS-CoV-2 vaccination: a population-based cohort study.

BACKGROUND: Postmarketing evaluations have linked myocarditis to SARS-CoV-2 mRNA vaccines. We sought to estimate the incidence of myocarditis after mRNA vaccination against SARS-CoV-2, and to compare the incidence with expected rates based on historical background rates in British Columbia. METHODS: We conducted an observational study using population health administrative data from the BC COVID-19 Cohort from Dec. 15, 2020, to Mar. 10, 2022. The primary exposure was any dose of an mRNA vaccine against SARS-CoV-2. The primary outcome was incidence of hospital admission or emergency department visit for myocarditis or myopericarditis within 7 and 21 days postvaccination, calculated as myocarditis rates per 100 000 mRNA vaccine doses, expected rates of myocarditis cases and observedto-expected ratios. We stratified analyses by age, sex, vaccine type and dose number. RESULTS: We observed 99 incident cases of myocarditis within 7 days (0.97 cases per 100 000 vaccine doses; observed v. expected ratio 14.81, 95% confidence interval [CI] 10.83-16.55) and 141 cases within 21 days (1.37 cases per 100 000 vaccine doses; observed v. expected ratio 7.03, 95% CI 5.92-8.29) postvaccination. Cases of myocarditis per 100 000 vaccine doses were higher for people aged 12-17 years (2.64, 95% CI 1.54-4.22) and 18-29 years (2.63, 95% CI 1.94-3.50) than for older age groups, for males compared with females (1.64, 95% CI 1.30-2.04 v. 0.35, 95% CI 0.21-0.55), for those receiving a second dose compared with a third dose (1.90, 95% CI 1.50-2.39 v. 0.76, 95% CI 0.45-1.30) and for those who received the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer-BioNTech) vaccine (1.44, 95% CI 1.06-1.91 v. 0.74, 95% CI 0.56-0.98). The highest observed-to-expected ratio was seen after the second dose among males aged 18-29 years who received the mRNA-1273 vaccine (148.32, 95% CI 95.03-220.69). INTERPRETATION: Although absolute rates of myocarditis were low, vaccine type, age and sex are important factors to consider when strategizing vaccine administration to reduce the risk of postvaccination myocarditis. Our findings support the preferential use of the BNT162b2 vaccine over the mRNA-1273 vaccine for people aged 18-29 years.

Comparative Risk of Myocarditis/Pericarditis Following Second Doses of BNT162b2 and mRNA-1273 Coronavirus Vaccines.

BACKGROUND: Postmarketing evaluations have linked myocarditis to COVID-19 mRNA vaccines. However, few population-based analyses have directly compared the safety of the 2 mRNA COVID-19 vaccines. OBJECTIVES: This study aimed to compare the risk of myocarditis, pericarditis, and myopericarditis between BNT162b2 and mRNA-1273. METHODS: We used data from the British Columbia COVID-19 Cohort (BCC19C), a population-based cohort study. The exposure was the second dose of an mRNA vaccine. The outcome was diagnosis of myocarditis, pericarditis, or myopericarditis during a hospitalization or an emergency department visit within 21 days of the second vaccination dose. We performed multivariable logistic regression to assess the association between vaccine product and the outcomes of interest. RESULTS: The rates of myocarditis and pericarditis per million second doses were higher for mRNA-1273 (n = 31, rate 35.6; 95% CI: 24.1-50.5; and n = 20, rate 22.9; 95% CI: 14.0-35.4, respectively) than BNT162b2 (n = 28, rate 12.6; 95% CI: 8.4-18.2 and n = 21, rate 9.4; 95% CI: 5.8-14.4, respectively). mRNA-1273 vs BNT162b2 had significantly higher odds of myocarditis (adjusted OR [aOR]: 2.78; 95% CI: 1.67-4.62), pericarditis (aOR: 2.42; 95% CI: 1.31-4.46) and myopericarditis (aOR: 2.63; 95% CI: 1.76-3.93). The association between mRNA-1273 and myocarditis was stronger for men (aOR: 3.21; 95% CI: 1.77-5.83) and younger age group (18-39 years; aOR: 5.09; 95% CI: 2.68-9.66). CONCLUSIONS: Myocarditis/pericarditis following mRNA COVID-19 vaccines is rare, but we observed a 2- to 3-fold higher odds among individuals who received mRNA-1273 vs BNT162b2. The rate of myocarditis following mRNA-1273 receipt is highest among younger men (age 18-39 years) and does not seem to be present at older ages. Our findings may have policy implications regarding the choice of vaccine offered.

Cohort profile: the British Columbia COVID-19 Population Mixing Patterns Survey (BC-Mix).

PURPOSE: Several non-pharmaceutical interventions, such as physical distancing, handwashing, self-isolation, and school and business closures, were implemented in British Columbia (BC) following the first laboratory-confirmed case of COVID-19 on 26 January 2020, to minimise in-person contacts that could spread infections. The BC COVID-19 Population Mixing Patterns Survey (BC-Mix) was established as a surveillance system to measure behaviour and contact patterns in BC over time to inform the timing of the easing/re-imposition of control measures. In this paper, we describe the BC-Mix survey design and the demographic characteristics of respondents. PARTICIPANTS: The ongoing repeated online survey was launched in September 2020. Participants are mainly recruited through social media platforms (including Instagram, Facebook, YouTube, WhatsApp). A follow-up survey is sent to participants 2-4 weeks after completing the baseline survey. Survey responses are weighted to BC's population by age, sex, geography and ethnicity to obtain generalisable estimates. Additional indices such as the Material and Social Deprivation Index, residential instability, economic dependency, and others are generated using census and location data. FINDINGS TO DATE: As of 26 July 2021, over 61 000 baseline survey responses were received of which 41 375 were eligible for analysis. Of the eligible participants, about 60% consented to follow-up and about 27% provided their personal health numbers for linkage with healthcare databases. Approximately 83.5% of respondents were female, 58.7% were 55 years or older, 87.5% identified as white and 45.9% had at least a university degree. After weighting, approximately 50% were female, 39% were 55 years or older, 65% identified as white and 50% had at least a university degree. FUTURE PLANS: Multiple papers describing contact patterns, physical distancing measures, regular handwashing and facemask wearing, modelling looking at impact of physical distancing measures and vaccine acceptance, hesitancy and uptake are either in progress or have been published.

Mental Health and Substance Use Associated with Hospitalization among People with COVID-19: A Population-Based Cohort Study.

This study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. The study used data from the BC COVID-19 Cohort, which integrates data on all COVID-19 cases with data on hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia to 15 January 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance. Of the 56,874 COVID-19 cases included in the analysis, 2298 were hospitalized. Factors associated with increased hospitalization risk were as follows: male sex (adjusted risk ratio (aRR) = 1.27; 95% CI = 1.17-1.37), older age (p-trend < 0.0001 across age groups increasing hospitalization risk with increasing age [aRR 30-39 years = 3.06; 95% CI = 2.32-4.03, to aRR 80+ years = 43.68; 95% CI = 33.41-57.10 compared to 20-29 years-old]), asthma (aRR = 1.15; 95% CI = 1.04-1.26), cancer (aRR = 1.19; 95% CI = 1.09-1.29), chronic kidney disease (aRR = 1.32; 95% CI = 1.19-1.47), diabetes (treated without insulin aRR = 1.13; 95% CI = 1.03-1.25, requiring insulin aRR = 5.05; 95% CI = 4.43-5.76), hypertension (aRR = 1.19; 95% CI = 1.08-1.31), injection drug use (aRR = 2.51; 95% CI = 2.14-2.95), intellectual and developmental disabilities (aRR = 1.67; 95% CI = 1.05-2.66), problematic alcohol use (aRR = 1.63; 95% CI = 1.43-1.85), immunosuppression (aRR = 1.29; 95% CI = 1.09-1.53), and schizophrenia and psychotic disorders (aRR = 1.49; 95% CI = 1.23-1.82). In an analysis restricted to women of reproductive age, pregnancy (aRR = 2.69; 95% CI = 1.42-5.07) was associated with increased risk of hospital admission. Older age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization.