[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.