[Clinical Infectious Diseases, 1 February 2023]

Background: In late 2021, the Omicron severe acute respiratory syndrome coronavirus 2 variant emerged and rapidly replaced Delta as the dominant variant. The increased transmissibility of Omicron led to surges in case rates and hospitalizations; however, the true severity of the variant remained unclear. We aimed to provide robust estimates of Omicron severity relative to Delta.

Methods: This retrospective cohort study was conducted with data from the British Columbia COVID-19 Cohort, a large provincial surveillance platform with linkage to administrative datasets. To capture the time of cocirculation with Omicron and Delta, December 2021 was chosen as the study period. Whole-genome sequencing was used to determine Omicron and Delta variants. To assess the severity (hospitalization, intensive care unit [ICU] admission, length of stay), we conducted adjusted Cox proportional hazard models, weighted by inverse probability of treatment weights (IPTW).

Results: The cohort was composed of 13 128 individuals (7729 Omicron and 5399 Delta). There were 419 coronavirus disease 2019 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 with Delta (adjusted hazard ratio [aHR] = 0.50, 95% confidence interval [CI] = 0.43 to 0.59), a 73% lower risk of ICU admission (aHR = 0.27, 95% CI = 0.19 to 0.38), and a 5-day shorter hospital stay (aß = −5.03, 95% CI = −8.01 to −2.05).

Conclusions: Our analysis supports findings from other studies that have demonstrated lower risk of severe outcomes in Omicron-infected individuals relative to Delta.

[BMJ Open Respiratory Research, 2 February 2023]

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.

[JMIR Public Health and Surveillance, 11 January 2023]

Background: Face mask use has been associated with declines in COVID-19 incidence rates worldwide. A handful of studies have examined the factors associated with face mask use in North America during the COVID-19 pandemic; however, much less is known about the patterns of face mask use and the impact of mask mandates during this time. This information could have important policy implications, now and in the event of future pandemics.

Objective: To address existing knowledge gaps, we assessed face mask usage patterns among British Columbia COVID-19 Population Mixing Patterns (BC-Mix) survey respondents and evaluated the impact of the provincial mask mandate on these usage patterns.

Methods: Between September 2020 and July 2022, adult British Columbia residents completed the web-based BC-Mix survey, answering questions on the circumstances surrounding face mask use or lack thereof, movement patterns, and COVID-19–related beliefs. Trends in face mask use over time were assessed, and associated factors were evaluated using multivariable logistic regression. A stratified analysis was done to examine effect modification by the provincial mask mandate.

Results: Of the 44,301 respondents, 81.9% reported wearing face masks during the 23-month period. In-store and public transit mask mandates supported monthly face mask usage rates of approximately 80%, which was further bolstered up to 92% with the introduction of the provincial mask mandate. Face mask users mostly visited retail locations (51.8%) and travelled alone by car (49.6%), whereas nonusers mostly traveled by car with others (35.2%) to their destinations—most commonly parks (45.7%). Nonusers of face masks were much more likely to be male than female, especially in retail locations and restaurants, bars, and cafés. In a multivariable logistic regression model adjusted for possible confounders, factors associated with face mask use included age, ethnicity, health region, mode of travel, destination, and time period. The odds of face mask use were 3.68 times greater when the provincial mask mandate was in effect than when it was not (adjusted odds ratio [aOR] 3.68, 95% CI 3.33-4.05). The impact of the mask mandate was greatest in restaurants, bars, or cafés (mandate: aOR 7.35, 95% CI 4.23-12.78 vs no mandate: aOR 2.81, 95% CI 1.50-5.26) and in retail locations (mandate: aOR 19.94, 95% CI 14.86-26.77 vs no mandate: aOR 7.71, 95% CI 5.68-10.46).

Conclusions: Study findings provide added insight into the dynamics of face mask use during the COVID-19 pandemic. Mask mandates supported increased and sustained high face mask usage rates during the first 2 years of the pandemic, having the greatest impact in indoor public locations with limited opportunity for physical distancing targeted by these mandates. These findings highlight the utility of mask mandates in supporting high face mask usage rates during the COVID-19 pandemic.

[Clinical Microbiology, 10 January 2023]

We compared the seroprevalence of SARS-CoV-2 anti-nucleocapsid antibodies in blood donors across Canadian regions in 2021. The seroprevalence was the highest in Alberta and the Prairies, and it was so low in Atlantic Canada that few correlates were observed. Being male and of young age were predictive of seropositivity. Racialization was associated with higher seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. Living in a materially deprived neighborhood predicted higher seroprevalence, but it was more linear across quintiles in Alberta and the Prairies, whereas in British Columbia and Ontario, the most affluent 60% were similarly low and the most deprived 40% similarly elevated. Living in a more socially deprived neighborhood (more single individuals and one parent families) was associated with lower seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. These data show striking variability in SARS-CoV-2 seroprevalence across regions by social determinants of health.

[International Journal of Infectious Diseases, February 2023]

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.

[CMAJ, 21 November 2022]

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.

As of September 2022, more than 32 million people in Canada, including around 4.5 million in British Columbia, have received a vaccine to prevent SARS-CoV-2 infection.1 With any novel vaccine, safety and effectiveness are important to public health and may determine the success of achieving the targeted immunization coverage. According to a recent systematic review, the overall rate of SARS-CoV-2 vaccination acceptance ranges from 53.6% to 84.4% in the United States.2 One of the key reasons for vaccine hesitancy is the fear of adverse effects.3,4

As large populations are vaccinated, certain uncommon events may be observed that were not detected during the premarketing clinical trials, whether or not these events are related to the vaccine. The same is the case with SARS-CoV-2 vaccination. The prelicensure study data did not suggest any risk of postvaccination myocarditis. However, postmarketing studies have suggested an association between mRNA SARS-CoV-2 vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) and myocarditis, among other adverse events after immunization, which has raised concern regarding the safety of mRNA vaccines, specifically among younger populations.5–7 Most evidence comes from case reports and case series. Earlier data have suggested higher rates of myocarditis among young adults after the mRNA-1273 compared with the BNT162b2 vaccine. Limited data are available on the rate of myocarditis after the third dose, which is relevant as further boosters are planned. Given the important economic and health consequences of COVID-19, it is vital to further evaluate the likelihood of this signal.

One of the pharmacoepidemiologic methods that refine a previously detected signal is an observed-to-expected analysis, which compares the number of cases observed or reported to a calculated number of cases expected under the null hypothesis of no association between the intervention and the disease.8 Thus, the primary objective of this study was to determine the incidence of patients who visited the emergency department or were admitted to the hospital with myocarditis after mRNA SARS-CoV-2 vaccination, and to compare these observed results to expected numbers based on historical rates before the rollout of SARS-CoV-2 vaccination.

[Journal of the American College of Cardiology, 7 November 2022]

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.

[Clinical Infectious Diseases, 1 August 2023]

Background: Antibiotics are frequently prescribed unnecessarily in outpatients with coronavirus disease 2019 (COVID-19). We sought to evaluate factors associated with antibiotic prescribing in outpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: We performed a population-wide cohort study of outpatients aged ≥66 years with polymerase chain reaction–confirmed SARS-CoV-2 from 1 January 2020 to 31 December 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1 week before (prediagnosis) and 1 week after (postdiagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary-series COVID-19 vaccination, in univariate and multivariable analyses.

Results: We identified 13 529 eligible nursing home residents and 50 885 eligible community-dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3020 (22%) and 6372 (13%), respectively, received at least 1 antibiotic prescription within 1 week of a SARS-CoV-2 positive result. Antibiotic prescribing in nursing home and community residents occurred, respectively, at 15.0 and 10.5 prescriptions per 1000 person-days prediagnosis and 20.9 and 9.8 per 1000 person-days postdiagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted postdiagnosis incidence rate ratios (95% confidence interval) of 0.7 (0.4–1) and 0.3 (0.3–0.4), respectively.

Conclusions: Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis but was reduced in COVID-19–vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19.

[Vaccine, 5 September 2023]

Background: The Global COVID Vaccine Safety (GCoVS) project was established in 2021 under the multinational Global Vaccine Data Network (GVDN) consortium to facilitate the rapid assessment of the safety of newly introduced vaccines. This study analyzed data from GVDN member sites on the background incidence rates of conditions designated as adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring.

Methods: Eleven GVDN global sites obtained data from national or regional healthcare databases using standardized methods. Incident events of 13 pre-defined AESI were included for a pre-pandemic period (2015–19) and the first pandemic year (2020). Background incidence rates (IR) and 95% confidence intervals (CI) were calculated for inpatient and emergency department encounters, stratified by age and sex, and compared between pre-pandemic and pandemic periods using incidence rate ratios.

Results: An estimated 197 million people contributed 1,189,652,926 person-years of follow-up time. Among inpatients in the pre-pandemic period (2015–19), generalized seizures were the most common neurological AESI (IR ranged from 22.15 [95% CI 19.01–25.65] to 278.82 [278.20–279.44] per 100,000 person-years); acute disseminated encephalomyelitis was the least common (<0.5 per 100,000 person-years at most sites). Pulmonary embolism was the most common thrombotic event (IR 45.34 [95% CI 44.85–45.84] to 93.77 [95% CI 93.46–94.08] per 100,000 person-years). The IR of myocarditis ranged from 1.60 [(95% CI 1.45–1.76) to 7.76 (95% CI 7.46–8.08) per 100,000 person-years. The IR of several AESI varied by site, healthcare setting, age and sex. The IR of some AESI were notably different in 2020 compared to 2015–19.

Conclusion: Background incidence of AESIs exhibited some variability across study sites and between pre-pandemic and pandemic periods. These findings will contribute to global vaccine safety surveillance and research.

[Journal of the International AIDS Society, 26 October 2023]

Introduction: People living with HIV (PLWH) and/or who inject drugs may experience lower vaccine effectiveness (VE) against SARS-CoV-2 infection.

Methods: A validated algorithm was applied to population-based, linked administrative datasets in the British Columbia COVID-19 Cohort (BCC19C) to ascertain HIV status and create a population of PLWH and matched HIV-negative individuals. The study population was limited to individuals who received an RT-PCR laboratory test for SARS-CoV-2 between 15 December 2020 and 21 November 2021 in BC, Canada. Any history of injection drug use (IDU) was ascertained using a validated administrative algorithm. We used a test-negative study design (modified case−control analysis) and multivariable logistic regression to estimate adjusted VE by HIV status and history of IDU.

Results: Our analysis included 2700 PLWH and a matched population of 375,043 HIV-negative individuals, among whom there were 351 and 103,049 SARS-CoV-2 cases, respectively. The proportion of people with IDU history was much higher among PLWH compared to HIV-negative individuals (40.7% vs. 4.3%). Overall VE during the first 6 months after second dose was lower among PLWH with IDU history (65.8%, 95% CI = 43.5–79.3) than PLWH with no IDU history (80.3%, 95% CI = 62.7–89.6), and VE was particularly low at 4–6 months (42.4%, 95% CI = −17.8 to 71.8 with IDU history vs. 64.0%; 95% CI = 15.7–84.7 without), although confidence intervals were wide. In contrast, overall VE was 88.6% (95% CI = 88.2–89.0) in the matched HIV-negative population with no history of IDU and remained relatively high at 4–6 months after second dose (84.6%, 95% CI = 83.8–85.4). Despite different patterns of vaccine protection by HIV status and IDU history, peak estimates were similar (≥88%) across all populations.

Conclusions: PLWH with a history of IDU may experience lower VE against COVID-19 infection, although findings were limited by a small sample size. The lower VE at 4–6 months may have implications for booster dose prioritization for PLWH and people who inject drugs. The immunocompromising effect of HIV, substance use and/or co-occurring comorbidities may partly explain these findings.

[International Journal of Infectious Diseases, 5 July 2023]

Objective: To examine the risk of hospitalization within 14 days of COVID-19 diagnosis among people living with HIV (PLWH) and HIV-negative individuals who had laboratory-confirmed SARS-CoV-2 infection.

Methods: We used Cox proportional hazard models to compare the relative risk of hospitalization in PLWH and HIV-negative individuals. Then, we used propensity score weighting to examine the influence of sociodemographic factors and comorbid conditions on risk of hospitalization. These models were further stratified by vaccination status and pandemic period (pre-Omicron: December 15, 2020, to November 21, 2021; Omicron: November 22, 2021, to October 31, 2022).

Results: The crude hazard ratio (HR) for risk of hospitalization in PLWH was 2.44 (95% confidence interval [CI]: 2.04-2.94). In propensity score-weighted models that included all covariates, the relative risk of hospitalization was substantially attenuated in the overall analyses (adjusted HR [aHR]: 1.03; 95% CI: 0.85-1.25), in vaccinated (aHR 1.00; 95% CI: 0.69-1.45), inadequately vaccinated (aHR: 1.04; 95% CI: 0.76-1.41) and unvaccinated individuals (aHR: 1.15; 95% CI: 0.84-1.56).

Conclusion: PLWH had about two times the risk of COVID-19 hospitalization than HIV-negative individuals in crude analyses which attenuated in propensity score-weighted models. This suggests that the risk differential can be explained by sociodemographic factors and history of comorbidity, underscoring the need to address social and comorbid vulnerabilities (e.g., injecting drugs) that were more prominent among PLWH.

[PLoS One, 2 June 2023]

Objectives: We sought to 1) identify long COVID phenotypes based on patient reported outcome measures (PROMs) and 2) determine whether the phenotypes were associated with quality of life (QoL) and/or lung function.

Methods: This was a longitudinal cohort study of hospitalized and non-hospitalized patients from March 2020 to January 2022 that was conducted across 4 Post-COVID Recovery Clinics in British Columbia, Canada. Latent class analysis was used to identify long COVID phenotypes using baseline PROMs (fatigue, dyspnea, cough, anxiety, depression, and post-traumatic stress disorder). We then explored the association between the phenotypes and QoL (using the EuroQoL 5 dimensions visual analogue scale [EQ5D VAS]) and lung function (using the diffusing capacity of the lung for carbon monoxide [DLCO]).

Results: There were 1,344 patients enrolled in the study (mean age 51 ±15 years; 780 [58%] were females; 769 (57%) were of a non-White race). Three distinct long COVID phenotypes were identified: Class 1) fatigue and dyspnea, Class 2) anxiety and depression, and Class 3) fatigue, dyspnea, anxiety, and depression. Class 3 had a significantly lower EQ5D VAS at 3 (50±19) and 6 months (54 ± 22) compared to Classes 1 and 2 (p<0.001). The EQ5D VAS significantly improved between 3 and 6 months for Class 1 (median difference of 6.0 [95% CI, 4.0 to 8.0]) and Class 3 (median difference of 5.0 [95% CI, 0 to 8.5]). There were no differences in DLCO between the classes.

Conclusions: There were 3 distinct long COVID phenotypes with different outcomes in QoL between 3 and 6 months after symptom onset. These phenotypes suggest that long COVID is a heterogeneous condition with distinct subpopulations who may have different outcomes and warrant tailored therapeutic approaches.

[JAMA Network Open, 18 April 2023]

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.

[PLoS Computational Biology, 12 May 2023]

The outbreak of the severe acute respiratory syndrome coronavirus 2 started in Wuhan, China, towards the end of 2019 and spread worldwide. The rapid spread of the disease can be attributed to many factors including its high infectiousness and the high rate of human mobility around the world. Although travel/movement restrictions and other non-pharmaceutical interventions aimed at controlling the disease spread were put in place during the early stages of the pandemic, these interventions did not stop COVID-19 spread. To better understand the impact of human mobility on the spread of COVID-19 between regions, we propose a hybrid gravity-metapopulation model of COVID-19. Our modeling framework has the flexibility of determining mobility between regions based on the distances between the regions or using data from mobile devices. In addition, our model explicitly incorporates time-dependent human mobility into the disease transmission rate, and has the potential to incorporate other factors that affect disease transmission such as facemasks, physical distancing, contact rates, etc. An important feature of this modeling framework is its ability to independently assess the contribution of each factor to disease transmission. Using a Bayesian hierarchical modeling framework, we calibrate our model to the weekly reported cases of COVID-19 in thirteen local health areas in Metro Vancouver, British Columbia (BC), Canada, from July 2020 to January 2021. We consider two main scenarios in our model calibration: using a fixed distance matrix and time-dependent weekly mobility matrices. We found that the distance matrix provides a better fit to the data, whilst the mobility matrices have the ability to explain the variance in transmission between regions. This result shows that the mobility data provides more information in terms of disease transmission than the distances between the regions.

[Pediatrics, 3 March 2023]

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.

[International Journal of Infectious Diseases, 24 March 2023]

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.

[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.

[The Lancet Gastroenterology and Hepatology, October 2023]

Background: The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infection as a public health threat by 2030; existing therapies and prophylaxis measures make such elimination feasible, even in the absence of a virological cure. We aimed to estimate the national, regional, and global prevalence of HBV in the general population and among children aged 5 years and younger, as well as the rates of diagnosis, treatment, prophylaxis, and the future burden globally.

Methods: In this modelling study, we used a Delphi process with data from literature reviews and interviews with country experts to quantify the prevalence, diagnosis, treatment, and prevention measures for HBV infection. The PRoGReSs Model, a dynamic Markov model, was used to estimate the country, regional, and global prevalence of HBV infection in 2022, and the effects of treatment and prevention on disease burden. The future incidence of morbidity and mortality in the absence of additional interventions was also estimated at the global level.

Findings: We developed models for 170 countries which resulted in an estimated global prevalence of HBV infection in 2022 of 3·2% (95% uncertainty interval 2·7–4·0), corresponding to 257·5 million (216·6–316·4) individuals positive for HBsAg. Of these individuals, 36·0 million were diagnosed, and only 6·8 million of the estimated 83·3 million eligible for treatment were on treatment. The prevalence among children aged 5 years or younger was estimated to be 0·7% (0·6–1·0), corresponding to 5·6 million (4·5–7·8) children with HBV infection. Based on the most recent data, 85% of infants received three-dose HBV vaccination before 1 year of age, 46% had received a timely birth dose of vaccine, and 14% received hepatitis B immunoglobulin along with the full vaccination regimen. 3% of mothers with a high HBV viral load received antiviral treatment to reduce mother-to-child transmission.

Interpretation: As 2030 approaches, the elimination targets remain out of reach for many countries under the current frameworks. Although prevention measures have had the most success, there is a need to increase these efforts and to increase diagnosis and treatment to work towards the elimination goals.

[Canadian Liver Journal, July 2023]

Background: Direct-acting antiviral (DAA) therapies have simplified HCV treatment, and publicly funded Canadian drug plans have eliminated disease-stage restrictions for reimbursement of DAA therapies. However other policies which complicate, delay, or prevent treatment initiation still persist. We aim to describe these plans’ existing reimbursement criteria and appraise whether they hinder treatment access.

Methods: We reviewed DAA reimbursement policies of 16 publicly funded drug plans published online and provided by contacts with in-depth knowledge of prescribing criteria. Data were collected from May to July 2022. Primary outcomes were: (1) if plans have arranged to accept point-of-care HCV RNA testing for diagnosis; testing requirements for (2) HCV genotype, (3) fibrosis stage, and (4) chronic infection; (5) time taken and method used to approve reimbursement requests; (6) providers eligible to prescribe DAAs; and (7) restrictions on re-treatment.

Results: Fifteen (94%) plans have at least one policy in place which limits simplified HCV treatment. Many plans continue to require results of genotype or fibrosis staging, limit eligible prescribers, and take longer than 1 day to approve coverage requests. One plan discourages treatment for re-infection.

Conclusion: Reimbursement criteria set by publicly funded Canadian drug plans continue to limit timely, equitable access to HCV treatment. Eliminating clinically irrelevant pre-authorization testing, expanding eligible prescribers, expediting claims processing, and broadening coverage of treatment for reinfection will improve access to DAAs. The federal government could further enhance efforts by introducing a federal HCV elimination strategy or federal high-cost drug PharmaCare program.

[The Lancet Regional Health - Americas, 29 December 2023]

Background: HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality.

Methods: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders.

Findings: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2–32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9–30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1–8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18–0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78–84%).

Interpretation: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health.

[Journal of Hepatology, 26 November 2023]

Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories.

Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level.

Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases.

Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.

Impact and implications: There is a great deal of uncertainty surrounding the prevalence of hepatitis delta virus among people living with hepatitis B virus at the population level. In this study, we aimed to better understand the burden in 25 countries and territories, to refine techniques that can be used in future analyses. We found a lower prevalence in the majority of places studied than had been previously reported. These data can help inform policy makers on the need to screen people living with hepatitis B virus to find those coinfected with hepatitis delta virus and at high risk of progression, while also highlighting the pitfalls that other researchers have often fallen into.