[Clinical Infectious Diseases, 1 February 2023]

Background: The rapid development of safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a singular scientific achievement. Confounding due to health-seeking behaviors, circulating variants, and differential testing by vaccination status may bias analyses toward an apparent increase in infection severity following vaccination.

Methods: We used data from the Ontario, Canada, Case and Contact Management Database and a provincial vaccination dataset (COVaxON) to create a time-matched cohort of individuals who were hospitalized with SARS-CoV-2 infection. Vaccinated individuals were matched to up to 5 unvaccinated individuals based on test date. Risk of intensive care unit (ICU) admission and death were evaluated using conditional logistic regression.

Results: In 20 064 individuals (3353 vaccinated and 16 711 unvaccinated) hospitalized with infection due to SARS-CoV-2 between 1 January 2021 and 5 January 2022, vaccination with 1, 2, or 3 doses significantly reduced the risk of ICU admission and death. An inverse dose–response relationship was observed between vaccine doses received and both outcomes (adjusted odds ratio [aOR] per additional dose for ICU admission, 0.66; 95% confidence interval [CI], .62 to .71; aOR for death, 0.78; 95% CI, .72 to .84).

Conclusions: We identified decreased virulence of SARS-CoV-2 infections in vaccinated individuals, even when vaccines failed to prevent infection sufficiently severe to cause hospitalization. Even with diminished efficacy of vaccines against infection with novel variants of concern, vaccines remain an important tool for reduction of ICU admission and mortality.

[Clinical Infectious Diseases, 1 February 2023]

Background: Pregnancy represents a physiological state associated with increased vulnerability to severe outcomes from infectious diseases, both for the pregnant person and developing infant. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than nonpregnant people to accept vaccination.

Methods: We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy using a population-based SARS-CoV-2 case file from Ontario, Canada. Because of varying propensity to receive vaccination, and changes in dominant circulating viral strains over time, a time-matched cohort study was performed to evaluate the relative risk of severe illness in pregnant women with SARS-CoV-2 compared to other SARS-CoV-2 infected women of childbearing age (10–49 years old). Risk of severe SARS-CoV-2 outcomes was evaluated in pregnant women and time-matched nonpregnant controls using multivariable conditional logistic regression.

Results: Compared with the rest of the population, nonpregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio, 1.28), whereas risk of infection was reduced among pregnant women (standardized morbidity ratio, 0.43). After adjustment for confounding, pregnant women had a markedly elevated risk of hospitalization (adjusted odds ratio, 4.96; 95% confidence interval, 3.86–6.37) and intensive care unit admission (adjusted odds ratio, 6.58; 95% confidence interval, 3.29–13.18). The relative increase in hospitalization risk associated with pregnancy was greater in women without comorbidities than in those with comorbidities (P for heterogeneity, .004).

Conclusions: Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favors SARS-CoV-2 vaccination in pregnant women.

[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.

[BIOMATH, 27 January 2023]

We investigate a model of the early stage of the COVID-19 epidemic comprising undetected infected individuals as well as behavioural change towards the use of self-protection measures. The model is fitted to China data reported between 22 January and 29 June 2020. Using fitting results, we then consider model responses to varying screening intensities.

[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.

[Int. J. Environ. Res. Public Health, 10 January 2023]

Throughout the COVID-19 pandemic, numerous non-human species were shown to be susceptible to natural infection by SARS-CoV-2, including farmed American mink. Once infected, American mink can transfer the virus from mink to human and mink to mink, resulting in a high rate of viral mutation. Therefore, outbreak surveillance on American mink farms is imperative for both mink and human health. Historically, disease surveillance on mink farms has consisted of a combination of mortality and live animal sampling; however, these methodologies have significant limitations. This study compared PCR testing of both deceased and live animal samples to environmental samples on an active outbreak premise, to determine the utility of environmental sampling. Environmental sampling mirrored trends in both deceased and live animal sampling in terms of percent positivity and appeared more sensitive in some low-prevalence instances. PCR CT values of environmental samples were significantly different from live animal samples’ CT values and were consistently high (mean CT = 36.2), likely indicating a low amount of viral RNA in the samples. There is compelling evidence in favour of environmental sampling for the purpose of disease surveillance, specifically as an early warning tool for SARS-CoV-2; however, further work is needed to ultimately determine whether environmental samples are viable sources for molecular epidemiology investigations.

[Epidemics, 25 January 2023]

Asymptomatic and symptomatic SARS-CoV-2 infections can have different characteristic time scales of transmission. These time-scale differences can shape outbreak dynamics as well as bias population-level estimates of epidemic strength, speed, and controllability. For example, prior work focusing on the initial exponential growth phase of an outbreak found that larger time scales for asymptomatic vs. symptomatic transmission can lead to under-estimates of the basic reproduction number as inferred from epidemic case data. Building upon this work, we use a series of nonlinear epidemic models to explore how differences in asymptomatic and symptomatic transmission time scales can lead to changes in the realized proportion of asymptomatic transmission throughout an epidemic. First, we find that when asymptomatic transmission time scales are longer than symptomatic transmission time scales, then the effective proportion of asymptomatic transmission increases as total incidence decreases. Moreover, these time-scale-driven impacts on epidemic dynamics are enhanced when infection status is correlated between infector and infectee pairs (e.g., due to dose-dependent impacts on symptoms). Next we apply these findings to understand the impact of time-scale differences on populations with age-dependent assortative mixing and in which the probability of having a symptomatic infection increases with age. We show that if asymptomatic generation intervals are longer than corresponding symptomatic generation intervals, then correlations between age and symptoms lead to a decrease in the age of infection during periods of epidemic decline (whether due to susceptible depletion or intervention). Altogether, these results demonstrate the need to explore the role of time-scale differences in transmission dynamics alongside behavioral changes to explain outbreak features both at early stages (e.g., in estimating the basic reproduction number) and throughout an epidemic (e.g., in connecting shifts in the age of infection to periods of changing incidence).

[Health Care Management Science, 24 January 2023]

Low rates of vaccination, emergence of novel variants of SARS-CoV-2, and increasing transmission relating to seasonal changes and relaxation of mitigation measures leave many US communities at risk for surges of COVID-19 that might strain hospital capacity, as in previous waves. The trajectories of COVID-19 hospitalizations differ across communities depending on their age distributions, vaccination coverage, cumulative incidence, and adoption of risk mitigating behaviors. Yet, existing predictive models of COVID-19 hospitalizations are almost exclusively focused on national- and state-level predictions. This leaves local policymakers in urgent need of tools that can provide early warnings about the possibility that COVID-19 hospitalizations may rise to levels that exceed local capacity. In this work, we develop a framework to generate simple classification rules to predict whether COVID-19 hospitalization will exceed the local hospitalization capacity within a 4- or 8-week period if no additional mitigating strategies are implemented during this time. This framework uses a simulation model of SARS-CoV-2 transmission and COVID-19 hospitalizations in the US to train classification decision trees that are robust to changes in the data-generating process and future uncertainties. These generated classification rules use real-time data related to hospital occupancy and new hospitalizations associated with COVID-19, and when available, genomic surveillance of SARS-CoV-2. We show that these classification rules present reasonable accuracy, sensitivity, and specificity (all ≥ 80%) in predicting local surges in hospitalizations under numerous simulated scenarios, which capture substantial uncertainties over the future trajectories of COVID-19. Our proposed classification rules are simple, visual, and straightforward to use in practice by local decision makers without the need to perform numerical computations.

[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.

[JAMA Network Open, 29 December 2022]

Importance: Lockdown measures and the stress of the COVID-19 pandemic are factors associated with increased risk of violence, yet there is limited information on trends in emergency department (ED) encounters for sexual assault.

Objective: To compare changes in ED encounters for sexual assault during the COVID-19 pandemic vs prepandemic estimates.

Design, Setting, and Participants: This retrospective, population-based cohort study used linked health administrative data from 197 EDs across Ontario, Canada, representing more than 15 million residents. Participants included all patients who presented to an ED in Ontario from January 11, 2019, to September 10, 2021. Male and female individuals of all ages were included. Data analysis was performed from March to October 2022.

Exposures: Sexual assault, defined through 27 International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, procedure and diagnoses codes.

Main Outcomes and Measures: Ten bimonthly time periods were used to compare differences in the frequency and rates of ED encounters for sexual assault between 2020 to 2021 (during the pandemic) compared with baseline prepandemic rates in 2019. Rate differences (RDs) and age adjusted rate ratios (aRRs) and Wald 95% CIs were calculated using Poisson regression.

Results: From January 11, 2019, to September 10, 2021, there were 14 476 656 ED encounters, including 10 523 for sexual assault (9304 [88.4%] among female individuals). The median (IQR) age was 23 (17-33) years for female individuals and 15 (4-29) years for male individuals. Two months before the pandemic, ED encounters increased for sexual assault among female individuals (8.4 vs 6.9 cases per 100 000; RD, 1.51 [95% CI, 1.06 to 1.96]; aRR, 1.22 [95% CI, 1.09 to 1.38]) and male individuals (1.2 vs 1.0 cases per 100 000; RD, 0.19 [95% CI, 0.05 to 0.36]; aRR, 1.19 [95% CI, 0.87 to 1.64]). During the first 2 months of the pandemic, the rates decreased for female individuals (4.2 vs 8.3 cases per 100 000; RD, −4.07 [95% CI, −4.48 to −3.67]; aRR, 0.51 [95% CI, 0.44 to 0.58]) and male individuals (0.5 vs 1.2 cases per 100 000; RD, −0.72 [95% CI, −0.86 to −0.57]; aRR, 0.39 [95% CI, 0.26 to 0.58]). For the remainder of the study period, the rates of sexual assault oscillated, returning to prepandemic levels during the summer months and between COVID-19 waves.

Conclusions and Relevance: These findings suggest that lockdown protocols should evaluate the impact of limited care for sexual assault. Survivors should still present to EDs, especially when clinical care or legal interventions are needed.

[JAMA Network Open, 28 December 2022]

Consensus exists among US transplant authorities to encourage COVID-19 vaccination in candidate organ recipients to minimize risk of posttransplant infection and increase odds of organ acceptance amid scarce organ resources.1 However, only 36% of US transplant centers require COVID-19 vaccination.2 While lifestyle and vaccination requirements are not new organ transplant conditions, the misinformation and public controversy surrounding COVID-19 policies may have led to misinformed or unbalanced portrayals of COVID-19 vaccines in the popular press.3 In this qualitative study, we examined newspaper coverage of the COVID-19 vaccination requirement for organ transplant to understand reporting portrayals.

[Journal of Theoretical Biology, 3 January 2023]

During the COVID-19 pandemic, some countries, such as Australia, China, Iceland, New Zealand, Thailand, and Vietnam successfully implemented an elimination strategy, enacting strict border control and periods of lockdowns to end community transmission. Atlantic Canada and Canada’s territories implemented similar policies, and reported long periods with no community cases. In Newfoundland and Labrador (NL), Nova Scotia, and Prince Edward Island a median of 80% or more of daily reported cases were travel-related from July 1, 2020 to May 31, 2021. With increasing vaccination coverage, it may be appropriate to exit an elimination strategy, but most existing epidemiological frameworks are applicable only to situations where most cases occur in the community, and are not appropriate for regions that have implemented an elimination strategy. To inform the pandemic response in regions that are implementing an elimination strategy, we extend importation modelling to consider post-arrival travel restrictions, and pharmaceutical and non-pharmaceutical interventions in the local community. We find that shortly after the Omicron variant had begun spreading in Canada, the expected daily number of spillovers, infections spread to NL community members from travellers and their close contacts, was higher than any time previously in the pandemic. By December 24, 2021, the expected number of spillovers was 44% higher than the previous high, which occurred in late July 2021 shortly after travel restrictions were first relaxed. We develop a method to assess the characteristics of potential future community outbreaks in regions that are implementing an elimination strategy. We apply this method to predict the effect of variant and vaccination coverage on the size of hypothetical community outbreaks in Mount Pearl, a suburb of the St. John’s metropolitan area in NL. Our methodology can be used to evaluate alternative plans to relax public health restrictions when vaccine coverage is high in regions that have implemented an elimination strategy. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”.

[Journal of Medical Virology, 22 December 2022]

The SARS-CoV-2 variant Omicron emerged in late 2021. In British Columbia (BC), Canada, and globally, three genetically distinct subvariants of Omicron, BA.1, BA.2, and BA.5, emerged and became dominant successively within an 8-month period. SARS-CoV-2 subvariants continue to circulate in the population, acquiring new mutations that have the potential to alter infectivity, immunity, and disease severity. Here, we report a propensity-matched severity analysis from residents of BC over the course of the Omicron wave, including 39,237 individuals infected with BA.1, BA.2, or BA.5 based on paired high-quality sequence data and linked to comprehensive clinical outcomes data between December 23, 2021 and August 31, 2022. Relative to BA.1, BA.2 cases were associated with a 15% and 28% lower risk of hospitalization and intensive care unit (ICU) admission (aHRhospital = 1.17; 95% confidence interval [CI] = 1.096–1.252; aHRICU = 1.368; 95% CI = 1.152–1.624), whereas BA.5 infections were associated with an 18% higher risk of hospitalization (aHRhospital = 1.18; 95% CI = 1.133–1.224) after accounting for age, sex, comorbidities, vaccination status, geography, and social determinants of health. Phylogenetic analysis revealed no specific subclades associated with more severe clinical outcomes for any Omicron subvariant. In summary, BA.1, BA.2, and BA.5 subvariants were associated with differences in clinical severity, emphasizing how variant-specific monitoring programs remain critical components of patient and population-level public health responses as the pandemic continues.

[The Lancet Global Health, January 2023]

Background: The WHO Strategic Advisory Group of Experts recommended that an extended interval of 3–5 years between the two doses of the human papillomavirus (HPV) vaccine could be considered to alleviate vaccine supply shortages. However, three concerns have limited the introduction of extended schedules: girls could be infected between the two doses, the vaccination coverage for the second dose could be lower at ages 13–14 years than at ages 9–10 years, and identifying girls vaccinated with a first dose to give them the second dose could be difficult. Using mathematical modelling, we examined the potential effect of these concerns on the population-level impact and efficiency of extended dose HPV vaccination schedules.

Methods: We used HPV-ADVISE, an individual-based, transmission-dynamic model of multitype HPV infection and disease, calibrated to country-specific data for four low-income and middle-income countries (India, Viet Nam, Uganda, and Nigeria). For the extended dose scenarios, we varied the vaccination coverage of the second dose among girls previously vaccinated, the one-dose vaccine efficacy, and the one-dose vaccine duration of protection. We also examined a strategy in which girls aged 14 years were vaccinated irrespective of their previous vaccination status. We used a scenario of girls-only two-dose vaccination at age 9 years (vaccine=9 valent, vaccine-type efficacy=100%, duration of protection=lifetime, and coverage=80%) as our comparator. We estimated two outcomes: the relative reduction in the age-standardised cervical cancer incidence (population-level impact) and the number of cervical cancers averted per 100 000 doses (efficiency).

Findings: Our model projected substantial reductions in cervical cancer incidence over 100 years with the two-dose schedule (79–86% depending on the country), compared with no vaccination. Projections for the 5-year extended schedule, in which the second dose is given only to girls previously vaccinated at age 9 years, were similar to the current two-dose schedule, unless vaccination coverage of the second dose is very low (reductions in cervical cancer incidence of 71–78% assuming 30% coverage at age 14 years among girls vaccinated at age 9 years). However, when the dose at age 14 years is given to girls irrespective of vaccination status and assuming high vaccination coverage, the model projected a substantially greater reduction in cervical cancer incidence compared with the current two-dose schedule (reductions in cervical cancer incidence of 86–93% assuming 70% coverage at age 14 years, irrespective of vaccination status). Efficiency of the extended schedule was greater than the two-dose schedule, even with a drop in vaccination coverage.

Interpretation: The three concerns are unlikely to have a substantial effect on the population-level impact of extended dose schedules. Hence, extended dose schedules will likely provide similar cervical cancer reductions as two-dose schedules, while reducing the number of doses required in the short-term, providing a more efficient use of scarce resources, and offering a 5-year time window to reassess the necessity of the second dose.

Funding: WHO, Canadian Institute of Health Research Foundation, Fonds de recherche du Québec–Santé, Digital Research Alliance of Canada, and Bill & Melinda Gates Foundation.

[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.

[CMAJ OPEN, 6 December 2022]

Background: SARS-CoV-2 transmission has an impact on education. In this study, we assessed the performance of rapid antigen detection tests (RADTs) versus polymerase chain reaction (PCR) for the diagnosis of SARS-CoV-2 infection in school settings, and RADT use for monitoring exposed contacts.

Methods: In this real-world, prospective observational cohort study, high-school students and staff were recruited from 2 high schools in Montréal, Canada, and followed from Jan. 25 to June 10, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared with those of other high schools in the same area.

Results: Overall, 2099 students and 286 school staff members consented to participate. The overall specificity of RADTs varied from 99.8% to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR result on days 6–7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 51 (72.5%) were secondary to household transmission, 13 (25.5%) to intraschool transmission, and 1 to community contacts between students in the same school.

Interpretation: Rapid antigen detection tests did not perform well compared with PCR in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADTs on the spot may avoid subsequent substantial exposures in class. Preprint: medRxiv — doi.org/10.1101/2021.10.13.21264960

Timely diagnosis of infection enables outbreak control through rapid isolation of index cases and subsequent contact tracing.1,2 Diagnosis of SARS-CoV-2 infection is predominantly based on polymerase chain reaction (PCR), which has a turnaround time of 24–48 hours. Rapid antigen detection tests (RADTs) are inexpensive and can be used at the point of care. They usually have high specificity and moderate sensitivity compared with PCR.3–6 Given their rapid turnaround time, RADTs allow for efficient triage and management of exposed individuals.7 The potential use of RADTs is especially relevant in schools, where outbreaks of SARS-CoV-2 infection can interrupt in-person teaching and negatively affect learning.8–11

Rapid antigen detection tests perform best in the early stages of infection, when viral load is generally high.12–15 Reported RADT sensitivity ranges from 28.9% to 98.3%, with improved sensitivity in samples with high viral loads and in symptomatic individuals.16,17 The usual limits of detection for PCR is 600–1000 viral RNA copies/mL, whereas RADTs usually have limits of detection 2–3 logs higher (105 to 106).18 Many studies have indicated the importance of high viral load dynamics with infectiousness. 19,20 For each unit increase in cycle threshold (Ct) value, the odds of recovering infectious virus decreased by 0.67, being under 10% when Ct values were greater than 35. Cycle threshold values of 17 to 32 corresponded to 105 and 101 SARS-CoV-2 RNA copies/μL, respectively.21

We aimed to determine the performance characteristics of RADTs for SARS-CoV-2 compared with PCR in high-school students and staff, and to determine whether serial testing of COVID-19 contacts would allow for safe faster return to school.

[International Journal of Infectious Diseases, February 2023]

Objectives: We estimated the effectiveness of COVID-19 vaccines against laboratory-confirmed SARS-CoV-2 infection among people living with HIV (PLWH) and compared the estimates with a matched HIV-negative cohort.

Methods: 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. The vaccine effectiveness (VE) was estimated with a test-negative design using the multivariable logistic regression.

Results: The adjusted VE against SARS-CoV-2 infection was 71.1% (39.7, 86.1%) 7-59 days after two doses, rising to 89.3% (72.2, 95.9%) between 60 and 89 days. VE was preserved 4-6 months after the receipt of two doses, after which noticeable waning was observed (51.3% [4.8, 75.0%]). In the matched HIV-negative cohort (n = 375,043), VE peaked at 91.4% (90.9, 91.8%) 7-59 days after two doses and was sustained for up to 4 months, after which evidence of waning was observed, dropping to 84.2% (83.4, 85.0%) between 4 and 6 months.

Conclusion: The receipt of two COVID-19 vaccine doses was effective against SARS-CoV-2 infection among PLWH pre-Omicron. VE estimates appeared to peak later in PLWH than in the matched HIV-negative cohort and the degree of waning was relatively quicker in PLWH; however, peak estimates were comparable in both populations.

[Clinical Infectious Diseases, December 2022]

Background: The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada’s larger provinces.

Methods: Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22–47) 2021.

Results: In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for ≥7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for ≥6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7–8-week versus manufacturer-specified 3–4-week intervals between mRNA doses.

Conclusions: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7–8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.

[Annals of Internal Medicine, December 2022]

Background: It is uncertain if medical masks offer similar protection against COVID-19 compared with N95 respirators.

Objective: To determine whether medical masks are noninferior to N95 respirators to prevent COVID-19 in health care workers providing routine care.

Design: Multicenter, randomized, noninferiority trial. (ClinicalTrials.gov: NCT04296643).

Setting: 29 health care facilities in Canada, Israel, Pakistan, and Egypt from 4 May 2020 to 29 March 2022.

Participants: 1009 health care workers who provided direct care to patients with suspected or confirmed COVID-19.

Intervention: Use of medical masks versus fit-tested N95 respirators for 10 weeks, plus universal masking, which was the policy implemented at each site.

Measurements: The primary outcome was confirmed COVID-19 on reverse transcriptase polymerase chain reaction (RT-PCR) test.

Results: In the intention-to-treat analysis, RT-PCR–confirmed COVID-19 occurred in 52 of 497 (10.46%) participants in the medical mask group versus 47 of 507 (9.27%) in the N95 respirator group (hazard ratio [HR], 1.14 [95% CI, 0.77 to 1.69]). An unplanned subgroup analysis by country found that in the medical mask group versus the N95 respirator group RT-PCR–confirmed COVID-19 occurred in 8 of 131 (6.11%) versus 3 of 135 (2.22%) in Canada (HR, 2.83 [CI, 0.75 to 10.72]), 6 of 17 (35.29%) versus 4 of 17 (23.53%) in Israel (HR, 1.54 [CI, 0.43 to 5.49]), 3 of 92 (3.26%) versus 2 of 94 (2.13%) in Pakistan (HR, 1.50 [CI, 0.25 to 8.98]), and 35 of 257 (13.62%) versus 38 of 261 (14.56%) in Egypt (HR, 0.95 [CI, 0.60 to 1.50]). There were 47 (10.8%) adverse events related to the intervention reported in the medical mask group and 59 (13.6%) in the N95 respirator group.

Limitation: Potential acquisition of SARS-CoV-2 through household and community exposure, heterogeneity between countries, uncertainty in the estimates of effect, differences in self-reported adherence, differences in baseline antibodies, and between-country differences in circulating variants and vaccination.

Conclusion: Among health care workers who provided routine care to patients with COVID-19, the overall estimates rule out a doubling in hazard of RT-PCR–confirmed COVID-19 for medical masks when compared with HRs of RT-PCR–confirmed COVID-19 for N95 respirators. The subgroup results varied by country, and the overall estimates may not be applicable to individual countries because of treatment effect heterogeneity.

[International Journal of Infectious Diseases, 28 November 2022]

Objectives: We examined the incremental protection and durability of infection-acquired immunity against Omicron infection in individuals with hybrid immunity in Ontario, Canada.

Methods: We followed up 6 million individuals with at least one multiplex reverse transcriptase–polymerase chain reaction test before November 21, 2021, until an Omicron infection. Protection via infection-acquired immunity was assessed by comparing Omicron infection risk between previously infected individuals and those without documented infection under different vaccination scenarios and stratified by time since the last infection or vaccination.

Results: A previous infection was associated with 68% (95% CI 61-73) and 43% (95% CI 27-56) increased protection against Omicron infection in individuals with two and three doses, respectively. Among individuals with two-dose vaccination, the incremental protection of infection-induced immunity decreased from 79% (95% CI 75-81) within 3 months after vaccination or infection to 27% (95% CI 14-37) at 9-11 months. In individuals with three-dose vaccination, it decreased from 57% (95% CI 50-63) within 3 months to 37% (95% CI 19-51) at 3-5 months after vaccination or infection.

Conclusion: Previous SARS-CovV-2 infections provide added cross-variant immunity to vaccination. Given the limited durability of infection-acquired protection in individuals with hybrid immunity, its influence on shield-effects at the population level and reinfection risks at the individual level may be limited.

[Experimental Biology and Medicine, 25 November 2022]

This editorial article aims to highlight advances in artificial intelligence (AI) technologies in five areas: Collaborative AI, Multimodal AI, Human-Centered AI, Equitable AI, and Ethical and Value-based AI in order to cope with future complex socioeconomic and public health issues.

[Journal of Theoretical Biology, 20 December 2022]

COVID-19 remains a major public health concern, with large resurgences even where there has been widespread uptake of vaccines. Waning immunity and the emergence of new variants will shape the long-term burden and dynamics of COVID-19. We explore the transition to the endemic state, and the endemic incidence in British Columbia (BC), Canada and South Africa (SA), to compare low and high vaccination coverage settings with differing public health policies, using a combination of modelling approaches. We compare reopening (relaxation of public health measures) gradually and rapidly as well as at different vaccination levels. We examine how the eventual endemic state depends on the duration of immunity, the rate of importations, the efficacy of vaccines and the transmissibility. These depend on the evolution of the virus, which continues to undergo selection. Slower reopening leads to a lower peak level of incidence and fewer overall infections in the wave following reopening: as much as a 60% lower peak and a 10% lower total in some illustrative simulations; under realistic parameters, reopening when 70% of the population is vaccinated leads to a large resurgence in cases. The long-term endemic behaviour may stabilize as late as January 2023, with further waves of high incidence occurring depending on the transmissibility of the prevalent variant, duration of immunity, and antigenic drift. We find that long term endemic levels are not necessarily lower than current pandemic levels: in a population of 100,000 with representative parameter settings (Reproduction number 5, 1-year duration of immunity, vaccine efficacy at 80% and importations at 3 cases per 100K per day) there are over 100 daily incident cases in the model. Predicted prevalence at endemicity has increased more than twofold after the emergence and spread of Omicron. The consequent burden on health care systems depends on the severity of infection in immunized or previously infected individuals.

[The Journal of Immunology, 15 November 2022]

Chronic infection with human CMV may contribute to poor vaccine efficacy in older adults. We assessed the effects of CMV serostatus on Ab quantity and quality, as well as cellular memory recall responses, after two and three SARS-CoV-2 mRNA vaccine doses, in older adults in assisted living facilities. CMV serostatus did not affect anti-Spike and anti–receptor-binding domain IgG Ab levels, nor neutralization capacity against wild-type or β variants of SARS-CoV-2 several months after vaccination. CMV seropositivity altered T cell expression of senescence-associated markers and increased effector memory re-expressing CD45RA T cell numbers, as has been previously reported; however, this did not impact Spike-specific CD4+ T cell memory recall responses. CMV-seropositive individuals did not have a higher incidence of COVID-19, although prior infection influenced humoral immunity. Therefore, CMV seropositivity may alter T cell composition but does not impede the durability of humoral protection or cellular memory responses after SARS-CoV-2 mRNA vaccination in older adults.

[PLoS Medicine, 10 November 2022]

Background: Our understanding of the global scale of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains incomplete: Routine surveillance data underestimate infection and cannot infer on population immunity; there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed SARS-CoV-2 seroprevalence studies, standardized to those described in the World Health Organization’s Unity protocol (WHO Unity) for general population seroepidemiological studies, to estimate the extent of population infection and seropositivity to the virus 2 years into the pandemic.

Methods and findings: We conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between January 1, 2020 and May 20, 2022. The review protocol is registered with PROSPERO (CRD42020183634). We included general population cross-sectional and cohort studies meeting an assay quality threshold (90% sensitivity, 97% specificity; exceptions for humanitarian settings). We excluded studies with an unclear or closed population sample frame. Eligible studies—those aligned with the WHO Unity protocol—were extracted and critically appraised in duplicate, with risk of bias evaluated using a modified Joanna Briggs Institute checklist. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate underascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% low- and middle-income countries [LMICs]) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/subnational scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1% to 62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6 to 28.8] to 86.7% [84.6% to 88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3% to 11.0%] in June 2020 to 95.9% [92.6% to 97.8%] in December 2021, in European high-income countries [HICs]). After the emergence of Omicron in March 2022, infection-induced seroprevalence rose to 47.9% [41.0% to 54.9%] in Europe HIC and 33.7% [31.6% to 36.0%] in Americas HIC. In 2021 Quarter Three (July to September), median seroprevalence to cumulative incidence ratios ranged from around 2:1 in the Americas and Europe HICs to over 100:1 in Africa (LMICs). Children 0 to 9 years and adults 60+ were at lower risk of seropositivity than adults 20 to 29 (p < 0.001 and p = 0.005, respectively). In a multivariable model using prevaccination data, stringent public health and social measures were associated with lower seroprevalence (p = 0.02). The main limitations of our methodology include that some estimates were driven by certain countries or populations being overrepresented.

Conclusions: In this study, we observed that global seroprevalence has risen considerably over time and with regional variation; however, over one-third of the global population are seronegative to the SARS-CoV-2 virus. Our estimates of infections based on seroprevalence far exceed reported Coronavirus Disease 2019 (COVID-19) cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.

[Frontiers in Public Health, 9 November 2022]

Background: Correctional workers are at increased risk of SARS-CoV-2 infection. We examined the seroprevalence of SARS-CoV-2, determined the effects of carceral and occupational exposures on seropositivity, and explored predictors of COVID-19 vaccine uptake among correctional workers in Quebec, Canada.

Methods: We conducted a cross-sectional seroprevalence study in three provincial prisons. The primary and secondary outcomes were SARS-CoV-2 antibody seropositivity (Roche Elecsys® serology test) and self-reported COVID-19 vaccination status (“fully vaccinated” defined as two doses or prior infection plus one dose), respectively. Poisson regression models with robust standard error were used to examine the effect of occupational variables with SARS-CoV-2 seropositivity and predictors of COVID-19 vaccine uptake. Estimates are presented as crude and adjusted prevalence ratios (aPR) with 95% confidence intervals (95% CI).

Results: From 14 July to 15 November 2021, 105/600 (18%) correctional workers tested positive across three prisons (range 11–21%); 76% were fully vaccinated. Seropositivity was affected by prison occupation (aPR 1.59, 95% CI 1.11–2.27 for correctional officers vs. all other occupations) and low perceived concern of SARS-CoV-2 acquisition (aPR 1.62, 95% CI 1.11–2.38 for not/hardly worried vs. somewhat/extremely worried). Predictors of being fully vaccinated included race/ethnicity (aPR 0.86, 95% CI 0.76–0.99 for visible minority vs. White), presence of comorbidities (aPR 1.14, 95% CI 1.02–1.28 for > 2 vs. none), and prison occupation (aPR 0.82, 95% CI 0.73–0.92 for correctional officers vs. all other occupations).

Conclusions: Correctional officers were most likely to have acquired SARS-CoV-2, but least likely to be vaccinated, underscoring the importance of addressing both occupational risks and COVID-19 vaccine hesitancy to mitigate future outbreaks.

[eLife, 8 November 2022]

Public health emergencies like SARS, MERS, and COVID-19 have prioritized surveillance of zoonotic coronaviruses, resulting in extensive genomic characterization of coronavirus diversity in bats. Sequencing viral genomes directly from animal specimens remains a laboratory challenge, however, and most bat coronaviruses have been characterized solely by PCR amplification of small regions from the best-conserved gene. This has resulted in limited phylogenetic resolution and left viral genetic factors relevant to threat assessment undescribed. In this study, we evaluated whether a technique called hybridization probe capture can achieve more extensive genome recovery from surveillance specimens. Using a custom panel of 20,000 probes, we captured and sequenced coronavirus genomic material in 21 swab specimens collected from bats in the Democratic Republic of the Congo. For 15 of these specimens, probe capture recovered more genome sequence than had been previously generated with standard amplicon sequencing protocols, providing a median 6.1-fold improvement (ranging up to 69.1-fold). Probe capture data also identified five novel alpha- and betacoronaviruses in these specimens, and their full genomes were recovered with additional deep sequencing. Based on these experiences, we discuss how probe capture could be effectively operationalized alongside other sequencing technologies for high-throughput, genomics-based discovery and surveillance of bat coronaviruses.

[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.

[Viruses, 31 October 2022]

Background: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time.

Methods: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n = 341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qPCR performed on self-collected nasopharyngeal specimens.

Results: Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14–56 days post-vaccination (p < 0.001) and vaccination prevented waning (regression coefficient, B = 1.66 [95%CI: 1.45–3.46]); while decline of nucleocapsid antibodies over time was observed (regression coefficient, B = −0.24 [95%CI: −1.2-(−0.12)]). A positive association was found between COVID-19 vaccination and endemic human β-coronavirus IgG titer 14–56 days post vaccination (OC43, p = 0.02 & HKU1, p = 0.02). On average, SARS-CoV-2 anti-spike IgG concentration increased in participants who received one vaccine dose by 2.06 log10 AU/mL (95%CI: 1.45–3.46) adjusting for age, biological sex, and time since infection. Cumulative incidence of high SARS-CoV-2 spike antibodies (>5.5 log10 AU/mL) was 83% greater in vaccinated compared to unvaccinated individuals.

Conclusions: Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination.

[Oikos, 25 October 2022]

Despite considerable study of population cycles, the striking variability of cycle periods in many cyclic populations has received relatively little attention. Mathematical models of cyclic population dynamics have historically exhibited much greater regularity in cycle periods than many real populations, even when accounting for environmental stochasticity. We contend, however, that the recent focus on understanding the impact of long, transient but recurrent epochs within population oscillations points the way to a previously unrecognized means by which environmental stochasticity can create cycle period variation. Specifically, consumer–resource cycles that bring the populations near a saddle point (a combination of population sizes toward which the populations tend, before eventually transitioning to substantially different levels) may be subject to a slow passage effect that has been dubbed a ‘saddle crawlby'. In this study, we illustrate how stochasticity that generates variability in how close predator and prey populations come to saddles can result in substantial variability in the durations of crawlbys and, as a result, in the periods of population cycles. Our work suggests a new mechanistic hypothesis to explain an important factor in the irregular timing of population cycles and provides a basis for understanding when environmental stochasticity is, and is not, expected to generate cyclic dynamics with variability across periods.

[eLife, 30 November 2022]

The role of schools in the spread of SARS-CoV-2 is controversial, with some claiming they are an important driver of the pandemic and others arguing that transmission in schools is negligible. School cluster reports that have been collected in various jurisdictions are a source of data about transmission in schools. These reports consist of the name of a school, a date, and the number of students known to be infected. We provide a simple model for the frequency and size of clusters in this data, based on random arrivals of index cases at schools who then infect their classmates with a highly variable rate, fitting the overdispersion evident in the data. We fit our model to reports from four Canadian provinces, providing estimates of mean and dispersion for cluster size, as well as the distribution of the instantaneous transmission parameter β, whilst factoring in imperfect ascertainment. According to our model with parameters estimated from the data, in all four provinces (i) more than 65% of non-index cases occur in the 20% largest clusters, and (ii) reducing instantaneous transmission rate and the number of contacts a student has at any given time are effective in reducing the total number of cases, whereas strict bubbling (keeping contacts consistent over time) does not contribute much to reduce cluster sizes. We predict strict bubbling to be more valuable in scenarios with substantially higher transmission rates.

[Epidemics, 26 October 2022]

Seroprevalence studies have been used throughout the COVID-19 pandemic to monitor infection and immunity. These studies are often reported in peer-reviewed journals, but the academic writing and publishing process can delay reporting and thereby public health action. Seroprevalence estimates have been reported faster in preprints and media, but with concerns about data quality. We aimed to (i) describe the timeliness of SARS-CoV-2 serosurveillance reporting by publication venue and study characteristics and (ii) identify relationships between timeliness, data validity, and representativeness to guide recommendations for serosurveillance efforts. We included seroprevalence studies published between January 1, 2020 and December 31, 2021 from the ongoing SeroTracker living systematic review. For each study, we calculated timeliness as the time elapsed between the end of sampling and the first public report. We evaluated data validity based on serological test performance and correction for sampling error, and representativeness based on the use of a representative sample frame and adequate sample coverage. We examined how timeliness varied with study characteristics, representativeness, and data validity using univariate and multivariate Cox regression. We analyzed 1844 studies. Median time to publication was 154 days (IQR 64–255), varying by publication venue (journal articles: 212 days, preprints: 101 days, institutional reports: 18 days, and media: 12 days). Multivariate analysis confirmed the relationship between timeliness and publication venue and showed that general population studies were published faster than special population or health care worker studies; there was no relationship between timeliness and study geographic scope, geographic region, representativeness, or serological test performance. Seroprevalence studies in peer-reviewed articles and preprints are published slowly, highlighting the limitations of using the academic literature to report seroprevalence during a health crisis. More timely reporting of seroprevalence estimates can improve their usefulness for surveillance, enabling more effective responses during health emergencies.

[JAMA Network Open, 13 March 2023]

Importance: People experiencing homelessness are at high risk of SARS-CoV-2 infection. Incident infection rates have yet to be established in these communities and are needed to inform infection prevention guidance and related interventions.

Objective: To quantify the SARS-CoV-2 incident infection rate among people experiencing homelessness in Toronto, Canada, in 2021 and 2022 and to assess factors associated with incident infection.

Design, Setting, and Participants: This prospective cohort study was conducted among individuals aged 16 years and older who were randomly selected between June and September 2021 from 61 homeless shelters, temporary distancing hotels, and encampments in Toronto, Canada.

Exposures: Self-reported housing characteristics, such as number sharing living space.

Main Outcomes and Measures: Prevalence of prior SARS-CoV-2 infection in summer 2021, defined as self-reported or polymerase chain reaction (PCR)– or serology-confirmed evidence of infection at or before the baseline interview, and SARS-CoV-2 incident infection, defined as self-reported or PCR- or serology-confirmed infection among participants without history of infection at baseline. Factors associated with infection were assessed using modified Poisson regression with generalized estimating equations.

Results: The 736 participants (415 of whom did not have SARS-CoV-2 infection at baseline and were included in the primary analysis) had a mean (SD) age of 46.1 (14.6) years; 486 (66.0%) self-identified as male. Of these, 224 (30.4% [95% CI, 27.4%-34.0%]) had a history of SARS-CoV-2 infection by summer 2021. Of the remaining 415 participants with follow-up, 124 experienced infection within 6 months, representing an incident infection rate of 29.9% (95% CI, 25.7%-34.4%), or 5.8% (95% CI, 4.8%-6.8%) per person-month. Report after onset of the SARS-CoV-2 Omicron variant was associated with incident infection, with an adjusted rate ratio (aRR) of 6.28 (95% CI, 3.94-9.99). Other factors associated with incident infection included recent immigration to Canada (aRR, 2.74 [95% CI, 1.64-4.58]) and alcohol consumption over the past interval (aRR, 1.67 [95% CI, 1.12-2.48]). Self-reported housing characteristics were not significantly associated with incident infection.

Conclusions and Relevance: In this longitudinal study of people experiencing homelessness in Toronto, SARS-CoV-2 incident infection rates were high in 2021 and 2022, particularly once the Omicron variant became dominant in the region. Increased focus on homelessness prevention is needed to more effectively and equitably protect these communities.

[BMC Genomics, 19 October 2022]

Background: The COVID-19 pandemic remains a global public health concern. Advances in sequencing technologies has allowed for high numbers of SARS-CoV-2 whole genome sequence (WGS) data and rapid sharing of sequences through global repositories to enable almost real-time genomic analysis of the pathogen. WGS data has been used previously to group genetically similar viral pathogens to reveal evidence of transmission, including methods that identify distinct clusters on a phylogenetic tree. Identifying clusters of linked cases can aid in the regional surveillance and management of the disease. In this study, we present a novel method for producing stable genomic clusters of SARS-CoV-2 cases, cov2clusters, and compare the accuracy and stability of our approach to previous methods used for phylogenetic clustering using real-world SARS-CoV-2 sequence data obtained from British Columbia, Canada.

Results: We found that cov2clusters produced more stable clusters than previously used phylogenetic clustering methods when adding sequence data through time, mimicking an increase in sequence data through the pandemic. Our method also showed high accuracy when predicting epidemiologically informed clusters from sequence data.

Conclusions: Our new approach allows for the identification of stable clusters of SARS-CoV-2 from WGS data. Producing high-resolution SARS-CoV-2 clusters from sequence data alone can a challenge and, where possible, both genomic and epidemiological data should be used in combination.

[AIDS, 1 December 2022]

Objective: People with HIV were underrepresented in coronavirus disease 2019 (COVID-19) vaccine clinical trials. We estimated vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for the BNT162b2, mRNA-1273, and ChAdOx1 vaccines among a population-based cohort of people with HIV in Ontario, Canada.

Design: Test-negative design

Methods: We identified people with HIV aged ≥19 years who were tested for SARS-CoV-2 by RT-PCR between December 14, 2020 (first availability of COVID-19 vaccines) and November 21, 2021 (pre-Omicron circulation). Outcomes included any infection, symptomatic infection, and COVID-19-related hospitalization/death. We compared the odds of vaccination between test-positive cases and test-negative controls using multivariable logistic regression with adjustment for age, sex, region, calendar time, SARS-CoV-2 test histories, influenza vaccination, comorbidities, and neighborhood-level socio-economic status. VE was derived as (1 – adjusted odds ratio) × 100%.

Results: Among 21 023 adults living with HIV, there were 801 (8.3%) test-positive cases and 8,879 (91.7%) test-negative controls. 20.1% cases and 47.8% of controls received ≥1 COVID-19 vaccine dose; among two-dose recipients, 93.4% received ≥1 mRNA dose. Two-dose VE ≥7 days before specimen collection was 82% (95% confidence interval [CI] = 74–87%) against any infection, 94% (95% CI = 82–98%) against symptomatic infection, and 97% (95% CI = 85–100%) against hospitalization/death. Against any infection, VE declined from 86% (95% CI = 77–92%) within 7–59 days after the second dose to 66% (95% CI = −15–90%) after ≥180 days; we did not observe evidence of waning protection for other outcomes.

Conclusion: Two doses of COVID-19 vaccine offered substantial protection against symptomatic illness and hospitalization/death in people with HIV prior to the emergence of the Omicron variant. Our findings do not support a broad conclusion that COVID-19 VE is lower among people with HIV in populations that, for the most part, are attending HIV care, taking antiretroviral medication, and are virally suppressed.

[JAMA Network Open, 14 October 2022]

Importance: The Omicron variant is phylogenetically and antigenically distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron reinfection, with and without vaccination, requires quantification.

Objective: To estimate the protection against Omicron reinfection and hospitalization conferred by prior heterologous non-Omicron SARS-CoV-2 infection and/or up to 3 doses of an ancestral, Wuhan-like messenger RNA (mRNA) vaccine.

Design, Setting, and Participants: This test-negative, population-based case-control study was conducted between December 26, 2021, and March 12, 2022, and included community-dwelling individuals aged 12 years or older who were tested for SARS-CoV-2 infection in the province of Quebec, Canada.

Exposures: Prior laboratory-confirmed SARS-CoV-2 infection with or without mRNA vaccination.

Main Outcomes and Measures: The main outcome was laboratory-confirmed SARS-CoV-2 reinfection and associated hospitalization, presumed to be associated with the Omicron variant according to genomic surveillance. The odds of prior infection with or without vaccination were compared for case participants with Omicron infection and associated hospitalizations vs test-negative control participants. Estimated protection was derived as 1 − the odds ratio, adjusted for age, sex, testing indication, and epidemiologic week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose.

Results: This study included 696 439 individuals (224 007 case participants and 472 432 control participants); 62.2% and 63.9% were female and 87.4% and 75.5% were aged 18 to 69 years, respectively. Prior non-Omicron SARS-CoV-2 infection was detected for 9505 case participants (4.2%) and 29 712 control participants (6.3%). Among nonvaccinated individuals, prior non-Omicron infection was associated with a 44% reduction (95% CI, 38%-48%) in Omicron reinfection risk, which decreased from 66% (95% CI, 57%-73%) at 3 to 5 months to 35% (95% CI, 21%-47%) at 9 to 11 months postinfection and was below 30% thereafter. The more severe the prior infection, the greater the risk reduction. Estimated protection (95% CI) against Omicron infection was consistently significantly higher among vaccinated individuals with prior infection compared with vaccinated infection-naive individuals, with 65% (63%-67%) vs 20% (16%-24%) for 1 dose, 68% (67%-70%) vs 42% (41%-44%) for 2 doses, and 83% (81%-84%) vs 73% (72%-73%) for 3 doses. For individuals with prior infection, estimated protection (95% CI) against Omicron-associated hospitalization was 81% (66%-89%) and increased to 86% (77%-99%) with 1, 94% (91%-96%) with 2, and 97% (94%-99%) with 3 mRNA vaccine doses, without signs of waning.

Conclusions and Relevance: The findings of this study suggest that vaccination with 2 or 3 mRNA vaccine doses among individuals with prior heterologous SARS-CoV-2 infection provided the greatest protection against Omicron-associated hospitalization. In the context of program goals to prevent severe outcomes and preserve health care system capacity, a third mRNA vaccine dose may add limited protection in twice-vaccinated individuals with prior SARS-CoV-2 infection.

[The Lancet Respiratory Medicine, December 2022]

Background: The large number of patients worldwide infected with the SARS-CoV-2 virus has overwhelmed health-care systems globally. The Anti-Coronavirus Therapies (ACT) outpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin for prevention of disease progression in community patients with COVID-19.

Methods: The ACT outpatient, open-label, 2 × 2 factorial, randomised, controlled trial, was done at 48 clinical sites in 11 countries. Patients in the community aged 30 years and older with symptomatic, laboratory confirmed COVID-19 who were within 7 days of diagnosis and at high risk of disease progression were randomly assigned (1:1) to receive colchicine 0·6 mg twice daily for 3 days and then 0·6 mg once daily for 25 days versus usual care, and in a second (1:1) randomisation to receive aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome was assessed at 45 days in the intention-to-treat population; for the colchicine randomisation it was hospitalisation or death, and for the aspirin randomisation it was major thrombosis, hospitalisation, or death. The ACT outpatient trial is registered at ClinicalTrials.gov, NCT04324463 and is ongoing.

Findings: Between Aug 27, 2020, and Feb 10, 2022, 3917 patients were randomly assigned to colchicine or control and to aspirin or control; after excluding 36 patients due to administrative reasons 3881 individuals were included in the analysis (n=1939 colchicine vs n=1942 control; n=1945 aspirin vs 1936 control). Follow-up was more than 99% complete. Overall event rates were 5 (0·1%) of 3881 for major thrombosis, 123 (3·2%) of 3881 for hospitalisation, and 23 (0·6%) of 3881 for death; 66 (3·4%) of 1939 patients allocated to colchicine and 65 (3·3%) of 1942 patients allocated to control experienced hospitalisation or death (hazard ratio [HR] 1·02, 95% CI 0·72–1·43, p=0·93); and 59 (3·0%) of 1945 of patients allocated to aspirin and 73 (3·8%) of 1936 patients allocated to control experienced major thrombosis, hospitalisation, or death (HR 0·80, 95% CI 0·57–1·13, p=0·21). Results for the primary outcome were consistent in all prespecified subgroups, including according to baseline vaccination status, timing of randomisation in relation to onset of symptoms (post-hoc analysis), and timing of enrolment according to the phase of the pandemic (post-hoc analysis). There were more serious adverse events with colchicine than with control (34 patients [1·8%] of 1939 vs 27 [1·4%] of 1942) but none in either group that led to discontinuation of study interventions. There was no increase in serious adverse events with aspirin versus control (31 [1·6%] vs 31 [1·6%]) and none that led to discontinuation of study interventions.

Interpretation: The results provide no support for the use of colchicine or aspirin to prevent disease progression or death in outpatients with COVID-19.

[The Lancet Respiratory Medicine, December 2022]

Background: COVID-19 disease is accompanied by a dysregulated immune response and hypercoagulability. The Anti-Coronavirus Therapies (ACT) inpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with the combination of rivaroxaban and aspirin for prevention of disease progression in patients hospitalised with COVID-19.

Methods: The ACT inpatient, open-label, 2 × 2 factorial, randomised, controlled trial was done at 62 clinical centres in 11 countries. Patients aged at least 18 years with symptomatic, laboratory confirmed COVID-19 who were within 72 h of hospitalisation or worsening clinically if already hospitalised were randomly assigned (1:1) to receive colchicine 1·2 mg followed by 0·6 mg 2 h later and then 0·6 mg twice daily for 28 days versus usual care; and in a second (1:1) randomisation, to the combination of rivaroxaban 2·5 mg twice daily plus aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome, assessed at 45 days in the intention-to-treat population, for the colchicine randomisation was the composite of the need for high-flow oxygen, mechanical ventilation, or death; and for the rivaroxaban plus aspirin randomisation was the composite of major thrombosis (myocardial infarction, stroke, acute limb ischaemia, or pulmonary embolism), the need for high-flow oxygen, mechanical ventilation, or death. The trial is registered at www.clinicaltrials.gov, NCT04324463 and is ongoing.

Findings: Between Oct 2, 2020, and Feb 10, 2022, at 62 sites in 11 countries, 2749 patients were randomly assigned to colchicine or control and the combination of rivaroxaban and aspirin or to the control. 2611 patients were included in the analysis of colchicine (n=1304) versus control (n=1307); 2119 patients were included in the analysis of rivaroxaban and aspirin (n=1063) versus control (n=1056). Follow-up was more than 98% complete. Overall, 368 (28·2%) of 1304 patients allocated to colchicine and 356 (27·2%) of 1307 allocated to control had a primary outcome (hazard ratio [HR] 1·04, 95% CI 0·90–1·21, p=0·58); and 281 (26·4%) of 1063 patients allocated to the combination of rivaroxaban and aspirin and 300 (28·4%) of 1056 allocated to control had a primary outcome (HR 0·92, 95% CI 0·78–1·09, p=0·32). Results were consistent in subgroups defined by vaccination status, disease severity at baseline, and timing of randomisation in relation to onset of symptoms. There was no increase in the number of patients who had at least one serious adverse event for colchicine versus control groups (87 [6·7%] of 1304 vs 90 [6·9%] of 1307) or with rivaroxaban and aspirin versus control groups (85 [8·0%] vs 91 [8·6%]). Among patients assigned to colchicine, 8 (0·61%) had adverse events that led to discontinuation of study drug, mostly gastrointestinal in nature. 17 (1·6%) patients assigned to the combination of rivaroxaban and aspirin had bleeding compared with seven (0·66%) of those allocated to control (p=0·042); the number of serious bleeding events was two (0·19%) versus six (0·57%), respectively (p=0·18). No patients assigned to rivaroxaban and aspirin had serious adverse events that led to discontinuation of study drug.

Interpretation: Among patients hospitalised with COVID-19, neither colchicine nor the combination of rivaroxaban and aspirin prevent disease progression or death.

[JMIR Public Health and Surveillance, 4 October 2022]

Background: Disproportionate risks of COVID-19 in congregate care facilities including long-term care homes, retirement homes, and shelters both affect and are affected by SARS-CoV-2 infections among facility staff. In cities across Canada, there has been a consistent trend of geographic clustering of COVID-19 cases. However, there is limited information on how COVID-19 among facility staff reflects urban neighborhood disparities, particularly when stratified by the social and structural determinants of community-level transmission.

Objective: This study aimed to compare the concentration of cumulative cases by geography and social and structural determinants across 3 mutually exclusive subgroups in the Greater Toronto Area (population: 7.1 million): community, facility staff, and health care workers (HCWs) in other settings.

Methods: We conducted a retrospective, observational study using surveillance data on laboratory-confirmed COVID-19 cases (January 23 to December 13, 2020; prior to vaccination rollout). We derived neighborhood-level social and structural determinants from census data and generated Lorenz curves, Gini coefficients, and the Hoover index to visualize and quantify inequalities in cases.

Results: The hardest-hit neighborhoods (comprising 20% of the population) accounted for 53.87% (44,937/83,419) of community cases, 48.59% (2356/4849) of facility staff cases, and 42.34% (1669/3942) of other HCW cases. Compared with other HCWs, cases among facility staff reflected the distribution of community cases more closely. Cases among facility staff reflected greater social and structural inequalities (larger Gini coefficients) than those of other HCWs across all determinants. Facility staff cases were also more likely than community cases to be concentrated in lower-income neighborhoods (Gini 0.24, 95% CI 0.15-0.38 vs 0.14, 95% CI 0.08-0.21) with a higher household density (Gini 0.23, 95% CI 0.17-0.29 vs 0.17, 95% CI 0.12-0.22) and with a greater proportion working in other essential services (Gini 0.29, 95% CI 0.21-0.40 vs 0.22, 95% CI 0.17-0.28).

Conclusions: COVID-19 cases among facility staff largely reflect neighborhood-level heterogeneity and disparities, even more so than cases among other HCWs. The findings signal the importance of interventions prioritized and tailored to the home geographies of facility staff in addition to workplace measures, including prioritization and reach of vaccination at home (neighborhood level) and at work.

[The Journal of Infectious Diseases, 15 September 2022]

Background: Third coronavirus disease 2019 (COVID-19) vaccine doses are broadly recommended, but immunogenicity data remain limited, particularly in older adults.

Methods: We measured circulating antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, ACE2 displacement, and virus neutralization against ancestral and omicron (BA.1) strains from prevaccine up to 1 month following the third dose, in 151 adults aged 24–98 years who received COVID-19 mRNA vaccines.

Results: Following 2 vaccine doses, humoral immunity was weaker, less functional, and less durable in older adults, where a higher number of chronic health conditions was a key correlate of weaker responses and poorer durability. One month after the third dose, antibody concentrations and function exceeded post–second-dose levels, and responses in older adults were comparable in magnitude to those in younger adults at this time. Humoral responses against omicron were universally weaker than against the ancestral strain after both the second and third doses. Nevertheless, after 3 doses, anti-omicron responses in older adults reached equivalence to those in younger adults. One month after 3 vaccine doses, the number of chronic health conditions, but not age, was the strongest consistent correlate of weaker humoral responses.

Conclusions: Results underscore the immune benefits of third COVID-19 vaccine doses, particularly in older adults.

[The Lancet Infectious Diseases, 21 September 2022]

Background: There is a paucity of data on vaccine-induced or infection-induced (hybrid or natural) immunity against omicron (B.1.1.529) subvariant BA.2, particularly in comparing the effects of previous SARS-CoV-2 infection with the same or different genetic lineage. We aimed to estimate the protection against omicron BA.2 associated with previous primary infection with omicron BA.1 or pre-omicron SARS-CoV-2, among health-care workers with and without mRNA vaccination.

Methods: We conducted a test-negative case-control study among health-care workers aged 18 years or older who were tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 was the predominant variant and was presumptively diagnosed with a positive test result. We identified cases (positive test during study period) and controls (negative test during study period) using the provincial laboratory database that records all nucleic acid amplification testing for SARS-CoV-2 in Quebec, and used the provincial immunisation registry to determine vaccination status. Logistic regression models compared the likelihood of BA.2 infection or reinfection (second positive test ≥30 days after primary infection) among health-care workers who had previous primary infection and none to three mRNA vaccine doses versus unvaccinated health-care workers with no primary infection.

Findings: 258 007 SARS-CoV-2 tests were done during the study period. Among those with a valid result and that met the inclusion criteria, there were 37 732 presumed BA.2 cases (2521 [6·7%] reinfections following pre-omicron primary infection and 659 [1·7%] reinfections following BA.1 primary infection) and 73 507 controls (7360 [10·0%] had pre-omicron primary infection and 12 315 [16·8%] had BA.1 primary infection). Pre-omicron primary infection was associated with a 38% (95% CI 19–53) reduction in BA.2 infection risk, with higher BA.2 protection among those who had also received one (56%, 95% CI 47–63), two (69%, 64–73), or three (70%, 66–74) mRNA vaccine doses. Omicron BA.1 primary infection was associated with greater protection against BA.2 infection (risk reduction of 72%, 95% CI 65–78), and protection was increased further among those who had received two doses of mRNA vaccine (96%, 95–96), but was not improved with a third dose (96%, 95–97).

Interpretation: Health-care workers who had received two doses of mRNA vaccine and had previous BA.1 infection were subsequently well protected for a prolonged period against BA.2 reinfection, with a third vaccine dose conferring no improvement to that hybrid protection. If this protection also pertains to future variants, there might be limited benefit from additional vaccine doses for people with hybrid immunity, depending on timing and variant.

[Clinical Microbiology, 20 September 2022]

There is evidence that COVID-19 convalescent plasma may improve outcomes of patients with impaired immune systems; however, more clinical trials are required. Although we have previously used a 50% plaque reduction/neutralization titer (PRNT50) assay to qualify convalescent plasma for clinical trials and virus-like particle (VLP) assays to validate PRNT50 methodologies, these approaches are time-consuming and expensive. Here, we characterized the ability of the Abbott severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG II Quant assay to identify high- and low-titer plasma for wild-type and variant (Alpha, Beta, Gamma, and Delta) SARS-CoV-2 characterized by both VLP assays and PRNT50. Plasma specimens previously tested in wild-type, Alpha, Beta, Gamma, and Delta VLP neutralization assays were selected based on availability. Selected specimens were evaluated by the Abbott SARS-CoV-2 IgG II Quant assay [Abbott anti-Spike (S); Abbott, Chicago, IL], and values in units per milliliter were converted to binding antibody units (BAU) per milliliter. Sixty-three specimens were available for analysis. Abbott SARS-CoV-2 IgG II Quant assay values in BAU per milliliter were significantly different between high- and low-titer specimens for wild-type (Mann-Whitney U = 42, P < 0.0001), Alpha (Mann-Whitney U = 38, P < 0.0001), Beta (Mann-Whitney U = 29, P < 0.0001), Gamma (Mann-Whitney U = 0, P < 0.0001), and Delta (Mann-Whitney U = 42, P < 0.0001). A conservative approach using the highest 95% confidence interval (CI) values from wild-type and variant of concern (VOC) SARS-CoV-2 experiments would identify a potential Abbott SARS-CoV-2 IgG II Quant assay cutoff of ≥7.1 × 103 BAU/mL.

IMPORTANCE: The United States Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the use of COVID-19 convalescent plasma (CCP) to treat hospitalized patients with COVID-19 in August 2020. However, by 4 February 2021, the FDA had revised the convalescent plasma EUA. This revision limited the authorization for high-titer COVID-19 convalescent plasma and restricted patient groups to hospitalized patients with COVID-19 early in their disease course or hospitalized patients with impaired humoral immunity. Traditionally our group utilized 50% plaque reduction/neutralization titer (PRNT50) assays to qualify CCP in Canada. Since that time, the Abbott SARS-CoV-2 IgG II Quant assay (Abbott, Chicago IL) was developed for the qualitative and quantitative determination of IgG against the SARS-CoV-2. Here, we characterized the ability of the Abbott SARS-CoV-2 IgG II Quant assay to identify high- and low-titer plasma for wild-type and variant (Alpha, Beta, Gamma, and Delta) SARS-CoV-2.

[Preventive Medicine Reports, December 2022]

The long-term dynamics of COVID-19 disease incidence and public health measures may impact individuals’ precautionary behaviours as well as support for measures. The objectives of this study were to assess longitudinal changes in precautionary behaviours and support for public health measures. Survey data were collected online from 1030 Canadians in each of 5 cycles in 2020: June 15-July 13; July 22-Aug 8; Sept 7–15; Oct 14–21; and Nov 12–17. Precautionary behaviour increased over the study period in the context of increasing disease incidence. When controlling for the stringency of public health measures and disease incidence, mixed effects logistic regression models showed these behaviours did not significantly change over time. Odds ratios for avoiding contact with family and friends ranged from 0.84 (95% CI 0.59–1.20) in September to 1.25 (95% CI 0.66–2.37) in November compared with July 2020. Odds ratios for attending an indoor gathering ranged from 0.86 (95% CI 0.62–1.20) in August to 1.71 (95% CI 0.95–3.09) in October compared with July 2020. Support for non-essential business closures increased over time with 2.33 (95% CI 1.14–4.75) times higher odds of support in November compared to July 2020. Support for school closures declined over time with lower odds of support in September (OR 0.66 [95% CI 0.45–0.96]), October (OR 0.48 [95% CI 0.26–0.87]), and November (OR 0.39 [95% CI 0.19–0.81]) compared with July 2020. In summary, respondents’ behaviour mirrored government guidance between July and November 2020 and supported individual precautionary behaviour and limitations on non-essential businesses over school closures.

[PLoS ONE, 9 September 2022]

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

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

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

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

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

[Frontiers in Immunology, 6 September 2022]

SARS-CoV-2 Omicron infections are common among individuals who are vaccinated or have recovered from prior variant infection, but few reports have immunologically assessed serial Omicron infections. We characterized SARS-CoV-2 humoral responses in an individual who acquired laboratory-confirmed Omicron BA.1.15 ten weeks after a third dose of BNT162b2, and BA.2 thirteen weeks later. Responses were compared to 124 COVID-19-naive vaccinees. One month post-second and -third vaccine doses, the participant’s wild-type and BA.1-specific IgG, ACE2-displacement and virus neutralization activities were average for a COVID-19-naive triple-vaccinated individual. BA.1 infection boosted the participant’s responses to the cohort ≥95th percentile, but even this strong “hybrid” immunity failed to protect against BA.2. Reinfection increased BA.1 and BA.2-specific responses only modestly. Though vaccines clearly protect against severe disease, results highlight the continued importance of maintaining additional protective measures to counteract the immune-evasive Omicron variant, particularly as vaccine-induced immune responses naturally decline over time.

[PLoS ONE, 29 August 2022]

Background: COVID-19 has rapidly emerged as a global public health threat with infections recorded in nearly every country. Responses to COVID-19 have varied in intensity and breadth, but generally have included domestic and international travel limitations, closure of non-essential businesses, and repurposing of health services. While these interventions have focused on testing, treatment, and mitigation of COVID-19, there have been reports of interruptions to diagnostic, prevention, and treatment services for other public health threats.

Objectives: We conducted a scoping review to characterize the early impact of COVID-19 on HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition.

Methods: A scoping literature review was completed using searches of PubMed and preprint servers (medRxiv/bioRxiv) from November 1st, 2019 to October 31st, 2020, using Medical Subject Headings (MeSH) terms related to SARS-CoV-2 or COVID-19 and HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition. Empiric studies reporting original data collection or mathematical models were included, and available data synthesized by region. Studies were excluded if they were not written in English.

Results: A total of 1604 published papers and 205 preprints were retrieved in the search. Overall, 8.0% (129/1604) of published studies and 10.2% (21/205) of preprints met the inclusion criteria and were included in this review: 7.3% (68/931) on HIV, 7.1% (24/339) on tuberculosis, 11.6% (26/224) on malaria, 7.8% (19/183) on sexual and reproductive health, and 9.8% (13/132) on malnutrition. Thematic results were similar across competing health risks, with substantial indirect effects of the COVID-19 pandemic and response on diagnostic, prevention, and treatment services for HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition.

Discussion: COVID-19 emerged in the context of existing public health threats that result in millions of deaths every year. Thus, effectively responding to COVID-19 while minimizing the negative impacts of COVID-19 necessitates innovation and integration of existing programs that are often siloed across health systems. Inequities have been a consistent driver of existing health threats; COVID-19 has worsened disparities, reinforcing the need for programs that address structural risks. The data reviewed here suggest that effective strengthening of health systems should include investment and planning focused on ensuring the continuity of care for both rapidly emergent and existing public health threats.

[The Journal of Infectious Diseases, 27 January 2022]

Background: In British Columbia, Canada, most adults 50–69 years old became eligible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in April 2021, with chimpanzee adenoviral vectored vaccine (ChAdOx1) restricted to ≥55-year-olds and second doses deferred ≥6 weeks to optimize single-dose coverage.

Methods: Among adults 50–69 years old, single-dose messenger RNA (mRNA) and ChAdOx1 vaccine effectiveness (VE) against SARS-CoV-2 infection and hospitalization, including variant-specific, was assessed by test-negative design between 4 April and 2 October 2021.

Results: Single-dose VE included 11 861 cases and 99 544 controls. Median of postvaccination follow-up was 32 days (interquartile range, 15–52 days). Alpha, Gamma, and Delta variants comprised 23%, 18%, and 56%, respectively, of genetically characterized viruses. At 21–55 days postvaccination, single-dose mRNA and ChAdOx1 VE (95% confidence interval [CI]) was 74% (71%–76%) and 59% (53%–65%) against any infection and 86% (80%–90%) and 94% (85%–97%) against hospitalization, respectively. VE (95% CI) was similar against Alpha and Gamma infections for mRNA (80% [76%–84%] and 80% [75%–84%], respectively) and ChAdOx1 (69% [60%–76%] and 66% [56%–73%], respectively). mRNA VE was lower at 63% (95% CI, 56%–69%) against Delta but 85% (95% CI, 71%–92%) against Delta-associated hospitalization (nonestimable for ChAdOx1).

Conclusions: A single mRNA or ChAdOx1 vaccine dose gave important protection against SARS-CoV-2, including early variants of concern. ChAdOx1 VE was lower against infection, but 1 dose of either vaccine reduced the hospitalization risk by >85% to at least 8 weeks postvaccination. Findings inform program options, including longer dosing intervals.

[Clinical Infectious Diseases, 1 July 2022]

Background: In Canada, first and second doses of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were uniquely spaced 16 weeks apart. We estimated 1- and 2-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Québec, Canada, including protection against varying outcome severity, variants of concern (VOCs), and the stability of single-dose protection up to 16 weeks postvaccination.

Methods: A test-negative design compared vaccination among SARS-CoV-2 test–positive and weekly matched (10:1), randomly sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by 1 dose ≥14 days or 2 doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression.

Results: Primary analysis included 5316 cases and 53 160 controls. Single-dose VE was 70% (95% confidence interval [CI], 68%–73%) against SARS-CoV-2 infection; 73% (95% CI, 71%–75%) against illness; and 97% (95% CI, 92%–99%) against hospitalization. Two-dose VE was 86% (95% CI, 81%–90%) and 93% (95% CI, 89%–95%), respectively, with no hospitalizations. VE was higher for non-VOCs than VOCs (73% Alpha) among single-dose recipients but not 2-dose recipients. Across 16 weeks, no decline in single-dose VE was observed, with appropriate stratification based upon prioritized vaccination determined by higher vs lower likelihood of direct patient contact.

Conclusions: One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least 4 months postvaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy.

[Clinical Infectious Diseases, 1 July 2022]

Background: Novel variants of concern (VOCs) have been associated with both increased infectivity and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virulence of SARS-CoV-2 is closely linked to age. Whether relative increases in virulence of novel VOCs are similar across the age spectrum or are limited to some age groups is unknown.

Methods: We created a retrospective cohort of people in Ontario, Canada, who tested positive for SARS-CoV-2 and were screened for VOCs (n = 259 984) between 7 February 2021 and 31 October 2021. Cases were classified as N501Y-positive VOC, probable Delta VOC, or VOC undetected. We constructed age-specific logistic regression models to evaluate associations between N501Y-postive or Delta VOC infections and infection severity using hospitalization, intensive care unit (ICU) admission, and death as outcome variables. Models were adjusted for sex, comorbidity, vaccination status, and temporal trends.

Results: Infection with either N501Y-positive or Delta VOCs was associated with significant elevations in risk of hospitalization, ICU admission, and death across age groups compared with infections where a VOC was not detected. The Delta VOC increased hospitalization risk in children aged <10 years by a factor of 2.5 (adjusted odds ratio; 95% confidence interval, 1.3 to 5.0) compared with non-VOCs. There was a significant inverse relationship between age and relative increase in risk of death with the Delta VOC, with younger age groups showing a greater relative increase in risk of death than older individuals.

Conclusions: SARS-CoV-2 VOCs appear to be associated with increased relative virulence of infection in all age groups, though low absolute numbers of outcomes in younger individuals make estimates in these groups imprecise.

[Clinical Infectious Diseases, 1 July 2022]

Background: People in prison are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We examined the seroprevalence of SARS-CoV-2 and associated carceral risk factors among incarcerated adult men in Quebec, Canada.

Methods: We conducted a cross-sectional seroprevalence study in 2021 across 3 provincial prisons, representing 45% of Quebec’s incarcerated male provincial population. The primary outcome was SARS-CoV-2 antibody seropositivity (Roche Elecsys serology test). Participants completed self-administered questionnaires on sociodemographic, clinical, and carceral characteristics. The association of carceral variables with SARS-CoV-2 seropositivity was examined using Poisson regression models with robust standard errors. Crude and adjusted prevalence ratios (aPR) with 95% confidence intervals (95% CIs) were calculated.

Results: Between 19 January 2021 and 15 September 2021, 246 of 1100 (22%) recruited individuals tested positive across 3 prisons (range, 15%–27%). Seropositivity increased with time spent in prison since March 2020 (aPR, 2.17; 95% CI, 1.53–3.07 for “all” vs “little time”), employment during incarceration (aPR, 1.64; 95% CI, 1.28–2.11 vs not), shared meal consumption during incarceration (“with cellmates”: aPR, 1.46; 95% CI, 1.08–1.97 vs “alone”; “with sector”: aPR, 1.34; 95% CI, 1.03–1.74 vs “alone”), and incarceration post-prison outbreak (aPR, 2.32; 95% CI, 1.69–3.18 vs “pre-outbreak”).

Conclusions: The seroprevalence of SARS-CoV-2 among incarcerated individuals was high and varied among prisons. Several carceral factors were associated with seropositivity, underscoring the importance of decarceration and occupational safety measures, individual meal consumption, and enhanced infection prevention and control measures including vaccination during incarceration.

[PLoS ONE, 31 March 2023]

Background: Vaccines against SARS-CoV-2 have been shown to reduce risk of infection as well as severe disease among those with breakthrough infection in adults. The latter effect is particularly important as immune evasion by Omicron variants appears to have made vaccines less effective at preventing infection. Therefore, we aimed to quantify the protection conferred by mRNA vaccination against hospitalization due to SARS-CoV-2 in adolescent and pediatric populations.

Methods: We retrospectively created a cohort of reported SARS-CoV-2 case records from Ontario’s Public Health Case and Contact Management Solution among those aged 4 to 17 linked to vaccination records from the COVaxON database on January 19, 2022. We used multivariable logistic regression to estimate the association between vaccination and hospitalization among SARS-CoV-2 cases prior to and during the emergence of Omicron.

Results: We included 62 hospitalized and 27,674 non-hospitalized SARS-CoV-2 cases, with disease onset from May 28, 2021 to December 4, 2021 (Pre-Omicron) and from December 23, 2021 to January 9, 2022 (Omicron). Among adolescents, two mRNA vaccine doses were associated with an 85% (aOR = 0.15; 95% CI: [0.04, 0.53]; p<0.01) lower likelihood of hospitalization among SARS-CoV-2 cases caused by Omicron. Among children, one mRNA vaccine dose was associated with a 79% (aOR = 0.21; 95% CI: [0.03, 0.77]; p<0.05) lower likelihood of hospitalization among SARS-CoV-2 cases caused by Omicron. The calculation of E-values, which quantifies how strong an unmeasured confounder would need to be to nullify our findings, suggest that these effects are unlikely to be explained by unmeasured confounding.

Conclusions: Despite immune evasion by SARS-CoV-2 variants, vaccination continues to be associated with a lower likelihood of hospitalization among adolescent and pediatric Omicron (B.1.1.529) SARS-CoV-2 cases, even when the vaccines do not prevent infection. Continued efforts are needed to increase vaccine uptake among adolescent and pediatric populations.

[Canada Communicable Disease Report, 31 May 2023]

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

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

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

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