[JAMA Network Open, 19 May 2023]

Importance: Adverse outcomes of COVID-19 in the pediatric population include disease and hospitalization, leading to school absenteeism. Booster vaccination for eligible individuals across all ages may promote health and school attendance.

Objective: To assess whether accelerating COVID-19 bivalent booster vaccination uptake across the general population would be associated with reduced pediatric hospitalizations and school absenteeism.

Design, Setting, and Participants: In this decision analytical model, a simulation model of COVID-19 transmission was fitted to reported incidence data from October 1, 2020, to September 30, 2022, with outcomes simulated from October 1, 2022, to March 31, 2023. The transmission model included the entire age-stratified US population, and the outcome model included children younger than 18 years.

Interventions: Simulated scenarios of accelerated bivalent COVID-19 booster campaigns to achieve uptake that was either one-half of or similar to the age-specific uptake observed for 2020 to 2021 seasonal influenza vaccination in the eligible population across all age groups.

Main Outcomes and Measures: The main outcomes were estimated hospitalizations, intensive care unit admissions, and isolation days of symptomatic infection averted among children aged 0 to 17 years and estimated days of school absenteeism averted among children aged 5 to 17 years under the accelerated bivalent booster campaign simulated scenarios.

Results: Among children aged 5 to 17 years, a COVID-19 bivalent booster campaign achieving age-specific coverage similar to influenza vaccination could have averted an estimated 5 448 694 (95% credible interval [CrI], 4 936 933-5 957 507) days of school absenteeism due to COVID-19 illness. In addition, the booster campaign could have prevented an estimated 10 019 (95% CrI, 8756-11 278) hospitalizations among the pediatric population aged 0 to 17 years, of which 2645 (95% CrI, 2152-3147) were estimated to require intensive care. A less ambitious booster campaign with only 50% of the age-specific uptake of influenza vaccination among eligible individuals could have averted an estimated 2 875 926 (95% CrI, 2 524 351-3 332 783) days of school absenteeism among children aged 5 to 17 years and an estimated 5791 (95% CrI, 4391-6932) hospitalizations among children aged 0 to 17 years, of which 1397 (95% CrI, 846-1948) were estimated to require intensive care.

Conclusions and Relevance: In this decision analytical model, increased uptake of bivalent booster vaccination among eligible age groups was associated with decreased hospitalizations and school absenteeism in the pediatric population. These findings suggest that although COVID-19 prevention strategies often focus on older populations, the benefits of booster campaigns for children may be substantial.

[arXiv, 23 June 2023]

We examine here the effects of recurrent vaccination and waning immunity on the establishment of an endemic equilibrium in a population. An individual-based model that incorporates memory effects for transmission rate during infection and subsequent immunity is introduced, considering stochasticity at the individual level. By letting the population size going to infinity, we derive a set of equations describing the large scale behavior of the epidemic. The analysis of the model's equilibria reveals a criterion for the existence of an endemic equilibrium, which depends on the rate of immunity loss and the distribution of time between booster doses. The outcome of a vaccination policy in this context is influenced by the efficiency of the vaccine in blocking transmissions and the distribution pattern of booster doses within the population. Strategies with evenly spaced booster shots at the individual level prove to be more effective in preventing disease spread compared to irregularly spaced boosters, as longer intervals without vaccination increase susceptibility and facilitate more efficient disease transmission. We provide an expression for the critical fraction of the population required to adhere to the vaccination policy in order to eradicate the disease, that resembles a well-known threshold for preventing an outbreak with an imperfect vaccine. We also investigate the consequences of unequal vaccine access in a population and prove that, under reasonable assumptions, fair vaccine allocation is the optimal strategy to prevent endemicity.

[Journal of Theoretical Biology, 26 May 2023]

The successive emergence of SARS-CoV-2 mutations has led to an unprecedented increase in COVID-19 incidence worldwide. Currently, vaccination is considered to be the best available solution to control the ongoing COVID-19 pandemic. However, public opposition to vaccination persists in many countries, which can lead to increased COVID-19 caseloads and hence greater opportunities for vaccine-evasive mutant strains to arise. To determine the extent that public opinion regarding vaccination can induce or hamper the emergence of new variants, we develop a model that couples a compartmental disease transmission framework featuring two strains of SARS-CoV-2 with game theoretical dynamics on whether or not to vaccinate. We combine semi-stochastic and deterministic simulations to explore the effect of mutation probability, perceived cost of receiving vaccines, and perceived risks of infection on the emergence and spread of mutant SARS-CoV-2 strains. We find that decreasing the perceived costs of being vaccinated and increasing the perceived risks of infection (that is, decreasing vaccine hesitation) will decrease the possibility of vaccine-resistant mutant strains becoming established by about fourfold for intermediate mutation rates. Conversely, we find increasing vaccine hesitation to cause both higher probability of mutant strains emerging and more wild-type cases after the mutant strain has appeared. We also find that once a new variant has emerged, perceived risk of being infected by the original variant plays a much larger role than perceptions of the new variant in determining future outbreak characteristics. Furthermore, we find that rapid vaccination under non-pharmaceutical interventions is a highly effective strategy for preventing new variant emergence, due to interaction effects between non-pharmaceutical interventions and public support for vaccination. Our findings indicate that policies that combine combating vaccine-related misinformation with non-pharmaceutical interventions (such as reducing social contact) will be the most effective for avoiding the establishment of harmful new variants.

[International Journal of Infectious Diseases, 28 February 2022]

Purpose: Given limited supplies of vaccines, having information on the costs, and associated health and economic impacts, is important for the development of optimal vaccination strategies. This study explores the epidemiological and economic impact, in terms of the value of lost production, of four vaccination strategies – fixed-dose interval (M1), prioritization of the first dose (M2), screen and forego vaccine for those with COVID-19 infection history (M3), and prioritization of the first dose along with screen and forego vaccine for those with COVID-19 infection history(M4), under constraints limiting the daily vaccine supply.

Methods & Materials: Using mathematical and statistical modelling, we quantified the number quarantined, hospitalization days, vaccine doses saved, and deaths averted, and production losses, for each strategy, in comparison to M1. The model parameters and initial conditions were based on Canadian data, and the simulation ran over 365 days starting from June 1, 2021. Sensitivity analyses explored how each strategy changes with different conditions of daily vaccine supply, the initial proportion recovered from COVID19 infection, and initial coverage of the first dose.

Results: Strategy M2 results in a reduction of 67,130,775 doses of vaccine administered, 20 lives saved, and a reduction of $3.8 billion of lost production in comparison to M1. M3 does not save any vaccine dose administered, but results in 5 lives saved, and a reduction of $575,149 in lost production in comparison to strategy M1. Due to the large proportion of the Canadian population who have already received a first vaccine dose, no screening actually occurs under scenario M3 and the daily vaccine supply was used entirely to provide second doses. While M2 is the dominant strategy under the current Canadian setting, sensitivity analyses revealed that M3 dominates when the vaccine supply increased or when the initial recovered proportion from COVID-19 was large enough.

Conclusion: The findings quantify the potential benefits of alternative vaccination strategies that can save lives and costs. Our study findings can help policymakers identify the optimal COVID19 vaccination strategy and our study framework can be adapted to other settings.

[Frontiers in Public Health, 4 January 2023]

The co-circulation of two respiratory infections with similar symptoms in a population can significantly overburden a healthcare system by slowing the testing and treatment. The persistent emergence of contagious variants of SARS-CoV-2, along with imperfect vaccines and their waning protections, have increased the likelihood of new COVID-19 outbreaks taking place during a typical flu season. Here, we developed a mathematical model for the co-circulation dynamics of COVID-19 and influenza, under different scenarios of influenza vaccine coverage, COVID-19 vaccine booster coverage and efficacy, and testing capacity. We investigated the required minimal and optimal coverage of COVID-19 booster (third) and fourth doses, in conjunction with the influenza vaccine, to avoid the coincidence of infection peaks for both diseases in a single season. We show that the testing delay brought on by the high number of influenza cases impacts the dynamics of influenza and COVID-19 transmission. The earlier the peak of the flu season and the greater the number of infections with flu-like symptoms, the greater the risk of flu transmission, which slows down COVID-19 testing, resulting in the delay of complete isolation of patients with COVID-19 who have not been isolated before the clinical presentation of symptoms and have been continuing their normal daily activities. Furthermore, our simulations stress the importance of vaccine uptake for preventing infection, severe illness, and hospitalization at the individual level and for disease outbreak control at the population level to avoid putting strain on already weak and overwhelmed healthcare systems. As such, ensuring optimal vaccine coverage for COVID-19 and influenza to reduce the burden of these infections is paramount. We showed that by keeping the influenza vaccine coverage about 35% and increasing the coverage of booster or fourth dose of COVID-19 not only reduces the infections with COVID-19 but also can delay its peak time. If the influenza vaccine coverage is increased to 55%, unexpectedly, it increases the peak size of influenza infections slightly, while it reduces the peak size of COVID-19 as well as significantly delays the peaks of both of these diseases. Mask-wearing coupled with a moderate increase in the vaccine uptake may mitigate COVID-19 and prevent an influenza outbreak.

[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.

[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.

[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.

[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.

[AIMS Mathematics, 13 December 2021]

As COVID-19 vaccines become available, different model-based approaches have been developed to evaluate strategic priorities for vaccine allocation to reduce severe illness. One strategy is to directly prioritize groups that are likely to experience medical complications due to COVID-19, such as older adults. A second strategy is to limit community spread by reducing importations, for example by vaccinating members of the mobile labour force, such as rotational workers. This second strategy may be appropriate for regions with low disease prevalence, where importations are a substantial fraction of all cases and reducing the importation rate reduces the risk of community outbreaks, which can provide significant indirect protection for vulnerable individuals. Current studies have focused on comparing vaccination strategies in the absence of importations, and have not considered allocating vaccines to reduce the importation rate. Here, we provide an analytical criteria to compare the reduction in the risk of hospitalization and intensive care unit (ICU) admission over four months when either older adults or rotational workers are prioritized for vaccination. Vaccinating rotational workers (assumed to be 6,000 individuals and about 1% of the Newfoundland and Labrador (NL) population) could reduce the average risk of hospitalization and ICU admission by 42%, if no community spread is observed at the time of vaccination, because epidemic spread is reduced and vulnerable individuals are indirectly protected. In contrast, vaccinating all individuals aged 75 and older (about 43,300 individuals, or 8% of the NL population) would lead to a 24% reduction in the average risk of hospitalization, and to a 45% reduction in the average risk of ICU admission, because a large number of individuals at high risk from COVID-19 are now vaccinated. Therefore, reducing the risk of hospitalization and ICU admission of the susceptible population by reducing case importations would require a significantly lower number of vaccines. Benefits of vaccinating rotational workers decrease with increasing infection prevalence in the community. Prioritizing members of the mobile labour force should be considered as an efficient strategy to indirectly protect vulnerable groups from COVID-19 exposure in regions with low disease prevalence.

[Clinical Infectious Diseases, 1 August 2023]

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

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

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

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

[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 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.

[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.

[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: 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.

[Vaccine, 16 September 2023]

Background: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2.

Methods: Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively.

Discussion: Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.

[Healthcare Policy, August 2023]

Background: This paper aims to assess the extent to which the COVID-19 vaccine's speed to market affected Canadian residents' decision to remain unvaccinated.

Method: A cross-sectional survey conducted in late 2021 asked participants whether they had received the vaccine and their reasons for abstaining.

Results: Of the 2,712 participants who completed the survey, 8.9% remained unvaccinated. Unvaccinated respondents who selected “They made the vaccine too fast” (59.8%), were significantly more likely to identify as white, believe that the COVID-19 pandemic was not serious and have an unvaccinated social circle.

Conclusion: Should the COVID-19 vaccine rapid regulatory process be expanded, more patients may refuse treatment than if traditional timelines are followed.

[Vaccine, 5 September 2023]

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

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

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

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

[Research Square, 4 May 2023]

Background: Vaccine hesitancy has seriously compromised the COVID-19 vaccine roll-out across the Western Pacific; nevertheless, evidence-based recommendations that account for the heterogeneity of vaccine-hesitant populations in this region remain lacking. To help design customized vaccine communication strategies, we sought to investigate the profile of the vaccine-hesitant populations in Cambodia, Japan, Lao PDR, Malaysia, Mongolia, Papua New Guinea, Philippines, Republic of Korea, and Viet Nam.

Methods: Using 16,408 survey responses from an international survey distributed in 2021 and 2022, we identified hidden subgroups by conducting latent class analysis (LCA) and examined their vaccine acceptance and booster uptake by using Ordinary Least Square (OLS) regressions.

Findings: Our LCA approach identified six classes: college students, distrusters of health care providers (HCPs), stay-at-home mothers, the elderly, compliant pragmatists, and general working population. Booster uptake were significantly low in two groups: college students [13 percentage points; 95% CI -0.21 to -0.05] and HCP distrusters [8 percentage points; 95% CI -0.15 to -0.01]; these groups’ acceptance were also similarly low. Stay-at-home mothers’ acceptance and uptake were comparable, but this group took a large portion of vaccine-hesitant people in the Philippines. The profiles of the vaccine-hesitant populations in each country were compared and categorized into four groups, depending on the composition of classes that account for the unvaccination population.

Interpretation: The results of this study suggest that drivers of vaccine hesitancy may vary by country and indicate that each country needs a customized strategy that reflects the profile of its vaccine-hesitant population. The proposed recommendations for each country can identify the target population for designing effective vaccine communication strategies.

[PLoS ONE, 22 September 2021]

Vaccinating individuals with more exposure to others can be disproportionately effective, in theory, but identifying these individuals is difficult and has long prevented implementation of such strategies. Here, we propose how the technology underlying digital contact tracing could be harnessed to boost vaccine coverage among these individuals. In order to assess the impact of this “hot-spotting” proposal we model the spread of disease using percolation theory, a collection of analytical techniques from statistical physics. Furthermore, we introduce a novel measure which we call the efficiency, defined as the percentage decrease in the reproduction number per percentage of the population vaccinated. We find that optimal implementations of the proposal can achieve herd immunity with as little as half as many vaccine doses as a non-targeted strategy, and is attractive even for relatively low rates of app usage.

[The Lancet Infectious Diseases, 7 October 2021]

In July, 2021, another wave of COVID-19 began in the USA as the highly infectious delta (B.1.617.2) SARS-CoV-2 variant drove outbreaks predominantly affecting states with relatively low vaccination coverage. Some US states have shown the feasibility of rapidly achieving high vaccination coverage. Specifically, an average of 74·0% of adults had been fully vaccinated in Vermont, Connecticut, Massachusetts, Maine, and Rhode Island by July 31. By contrast, two states facing substantial delta-driven surges, Florida and Texas, had fully vaccinated only 59·5% and 55·8% of their adult residents, respectively.1 Here, we estimate the deaths, hospital admissions, and infections that could have been averted if Florida and Texas had matched the average vaccination pace of the top-performing states and vaccinated 74·0% of their adult populations by the end of July.

[JAMA Network Open, 21 November 2022]

Importance: New York City, an early epicenter of the pandemic, invested heavily in its COVID-19 vaccination campaign to mitigate the burden of disease outbreaks. Understanding the return on investment (ROI) of this campaign would provide insights into vaccination programs to curb future COVID-19 outbreaks.

Objective: To estimate the ROI of the New York City COVID-19 vaccination campaign by estimating the tangible direct and indirect costs from a societal perspective.

Design, Setting, and Participants: This decision analytical model of disease transmission was calibrated to confirmed and probable cases of COVID-19 in New York City between December 14, 2020, and January 31, 2022. This simulation model was validated with observed patterns of reported hospitalizations and deaths during the same period.

Exposures: An agent-based counterfactual scenario without vaccination was simulated using the calibrated model.

Main Outcomes and Measures: Costs of health care and deaths were estimated in the actual pandemic trajectory with vaccination and in the counterfactual scenario without vaccination. The savings achieved by vaccination, which were associated with fewer outpatient visits, emergency department visits, emergency medical services, hospitalizations, and intensive care unit admissions, were also estimated. The value of a statistical life (VSL) lost due to COVID-19 death and the productivity loss from illness were accounted for in calculating the ROI.

Results: During the study period, the vaccination campaign averted an estimated $27.96 (95% credible interval [CrI], $26.19-$29.84) billion in health care expenditures and 315 724 (95% CrI, 292 143-340 420) potential years of life lost, averting VSL loss of $26.27 (95% CrI, $24.39-$28.21) billion. The estimated net savings attributable to vaccination were $51.77 (95% CrI, $48.50-$55.85) billion. Every $1 invested in vaccination yielded estimated savings of $10.19 (95% CrI, $9.39-$10.87) in direct and indirect costs of health outcomes that would have been incurred without vaccination.

Conclusions and Relevance: Results of this modeling study showed an association of the New York City COVID-19 vaccination campaign with reduction in severe outcomes and avoidance of substantial economic losses. This significant ROI supports continued investment in improving vaccine uptake during the ongoing pandemic.

[Journal of Global Health, September 2022]

Since the start of COVID-19 vaccination in the United States (US), over 560 million doses of authorized vaccines were administered, and 69.7% of the eligible population were fully vaccinated as of March 31, 2022 [1]. Much attention has focused on the public health toll of the pandemic. The positive impact of the rapid development and deployment of highly efficacious vaccines, ie, the reduction in deaths, hospitalizations, and health care costs, remains unclear. We estimated the reduction in COVID-19 cases, hospitalizations and mortality, as well as averted health care costs achieved by the vaccination program from December 12, 2020 to March 31, 2022.

[BMC Public Health, 27 June 2022]

Background: Mass immunization is a potentially effective approach to finally control the local outbreak and global spread of the COVID-19 pandemic. However, it can also lead to undesirable outcomes if mass vaccination results in increased transmission of effective contacts and relaxation of other public health interventions due to the perceived immunity from the vaccine.

Methods: We designed a mathematical model of COVID-19 transmission dynamics that takes into consideration the epidemiological status, public health intervention status (quarantined/isolated), immunity status of the population, and strain variations. Comparing the control reproduction numbers and the final epidemic sizes (attack rate) in the cases with and without vaccination, we quantified some key factors determining when vaccination in the population is beneficial for preventing and controlling future outbreaks.

Results: Our analyses predicted that there is a critical (minimal) vaccine efficacy rate (or a critical quarantine rate) below which the control reproduction number with vaccination is higher than that without vaccination, and the final attack rate in the population is also higher with the vaccination. We also predicted the worst case scenario occurs when a high vaccine coverage rate is achieved for a vaccine with a lower efficacy rate and when the vaccines increase the transmission efficient contacts.

Conclusions: The analyses show that an immunization program with a vaccine efficacy rate below the predicted critical values will not be as effective as simply investing in the contact tracing/quarantine/isolation implementation. We reached similar conclusions by considering the final epidemic size (or attack rates). This research then highlights the importance of monitoring the impact on transmissibility and vaccine efficacy of emerging strains.

[JAMA Network Open, 11 January 2022]

Introduction: The COVID-19 pandemic has caused more than 745 000 deaths in the US. However, the toll might have been higher without the rapid development and delivery of effective vaccines. As of October 28, 2021, 69% of 258 million US adults had been fully vaccinated.

Quantifying the population impact of COVID-19 vaccination can inform future vaccination strategies. Randomized clinical trials have established individual-level efficacy of authorized vaccines against the original strain, which exceeds 90% in preventing symptomatic and severe disease.1-3 However, the population-level effectiveness of the vaccination campaign in the US, in terms of association with reduced infections, hospitalizations, and deaths, is not as well documented, and we evaluated this using a simulation model.

Methods: This decision analytic model adheres to Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guideline. The institutional review of this study was waived by York University for the use of publicly available, deidentified data of the COVID-19 infections, deaths, and vaccination. Informed consent was not required to access the data.

We expanded our previous agent-based model4 to include transmission dynamics of the Alpha (B.1.1.7), Gamma (P.1), and Delta (B.1.617.2) variants in addition to the original strain (eMethods in the Supplement). The model was parameterized with the US demographics and age-specific risks of severe COVID-19 outcomes (eTable 1 and eTable 2 in the Supplement).5 A 2-dose vaccination strategy was implemented based on the daily vaccines administered in different age groups.6 Vaccine efficacies against infection, symptomatic disease and severe disease after each dose and for each variant were derived from published estimates (eTable 3 in the Supplement). The model was calibrated and fitted to reported national level incidence from October 1, 2020, to June 30, 2021 (eMethods in the Supplement).

We simulated pandemic trajectory under 2 counterfactuals: a no vaccination scenario and a program that achieved only half the daily vaccination rate of actual rollout. For each scenario, cumulative infections, hospitalizations, and deaths were compared with the simulated trends under the US vaccination program.

Credible intervals (CrIs) were generated from simulation outputs using the bias-corrected and accelerated bootstrap method (with 500 replications) in June 2021. The model was implemented in Julia Language Programming, version 1.6 (Julia), and outputs were analyzed in MATLAB, version 2017a (MathWorks). No significance tests were performed for this simulation study.

Results: Compared with the no vaccination scenario, the actual vaccination campaign saved an estimated 240 797 (95% CrI, 200 665-281 230) lives and prevented an estimated 1 133 617 (95% CrI, 967 487-1 301 881) hospitalizations from December 12, 2020, to June 30, 2021. The number of cases averted during the same period was projected to exceed 14 million. Vaccination prevented a wave of COVID-19 cases driven by the Alpha variant that would have occurred in April 2021 without vaccination (Figure 1), with a projected peak of 4409 (95% CrI, 2865-6312) deaths and 17 979 (95% CrI, 13 191-23 219) hospitalizations. Under the second counterfactual with daily vaccination rates at half the reported pace, we projected that the US would have still endured an additional 77 283 (95% CrI, 48 499-104 519) deaths and 336 000 (95% CrI, 225 330- 440 109) hospitalizations (Figure 2).

Discussion: Our analytical model suggested that the US COVID-19 vaccination program was associated with a reduction in the total hospitalizations and deaths by nearly half during the first 6 months of 2021. It was also associated with decreased impact of the more transmissible and lethal Alpha variant that was circulating during the same period. As new variants of SARS-CoV-2 continue to emerge, a renewed commitment to vaccine access, particularly among underserved groups and in counties with low vaccination coverage, will be crucial to preventing avoidable COVID-19 cases and bringing the pandemic to a close.

Limitations of our model included the use of reported cases for fitting, which may not reflect the true incidence. This fit does not completely match the temporal trends of reported hospitalizations and deaths. The model was nationally homogeneous; however, parameters may have varied across geographic regions. Furthermore, we did not consider waning immunity after vaccination or recovery within the study time frame.

[The Lancet Regional Health, 28 December 2022]

Background: The fourth wave of COVID-19 pandemic peaked in the US at 160,000 daily cases, concentrated primarily in southern states. As the Delta variant has continued to spread, we evaluated the impact of accelerated vaccination on reducing hospitalization and deaths across northeastern and southern regions of the US census divisions.

Methods: We used an age-stratified agent-based model of COVID-19 to simulate outbreaks in all states within two U.S. regions. The model was calibrated using reported incidence in each state from October 1, 2020 to August 31, 2021, and parameterized with characteristics of the circulating SARS-CoV-2 variants and state-specific daily vaccination rate. We then projected the number of infections, hospitalizations, and deaths that would be averted between September 2021 and the end of March 2022 if the states increased their daily vaccination rate by 20 or 50% compared to maintaining the status quo pace observed during August 2021.

Findings: A 50% increase in daily vaccine doses administered to previously unvaccinated individuals is projected to prevent a total of 30,727 hospitalizations and 11,937 deaths in the two regions between September 2021 and the end of March 2022. Southern states were projected to have a higher weighted average number of hospitalizations averted (18.8) and lives saved (8.3) per 100,000 population, compared to the weighted average of hospitalizations (12.4) and deaths (2.7) averted in northeastern states. On a per capita basis, a 50% increase in daily vaccinations is expected to avert the most hospitalizations in Kentucky (56.7 hospitalizations per 100,000 averted with 95% CrI: 45.56 - 69.9) and prevent the most deaths in Mississippi, (22.1 deaths per 100,000 population prevented with 95% CrI: 18.0 - 26.9).

Interpretation: Accelerating progress to population-level immunity by raising the daily pace of vaccination would prevent substantial hospitalizations and deaths in the US, even in those states that have passed a Delta-driven peak in infections.

Citerank: (7) 679878Seyed MoghadasSeyed Moghadas is an infectious disease modeller whose research includes mathematical and computational modelling in epidemiology and immunology. In particular, he is interested in the theoretical and computational aspects of mathematical models describing the underlying dynamics of infectious diseases, with a particular emphasis on establishing strong links between micro (individual) and macro (population) levels.10019D3ABAB, 701037MfPH – Publications144B5ACA0, 703963Mobility859FDEF6, 704045Covid-19859FDEF6, 704045Covid-19859FDEF6, 715328Nonpharmaceutical Interventions (NPIs)859FDEF6, 715831Diagnostic testing859FDEF6

[PNAS Nexus, 27 July 2022]

Quarantine and serial testing strategies for a disease depend principally on its incubation period and infectiousness profile. In the context of COVID-19, these primary public health tools must be modulated with successive SARS CoV-2 variants of concern that dominate transmission. Our analysis shows that (1) vaccination status of an individual makes little difference to the determination of the appropriate quarantine duration of an infected case, whereas vaccination coverage of the population can have a substantial effect on this duration, (2) successive variants can challenge disease control efforts by their earlier and increased transmission in the disease time course relative to prior variants, and (3) sufficient vaccine boosting of a population substantially aids the suppression of local transmission through frequent serial testing. For instance, with Omicron, increasing immunity through vaccination and boosters—for instance with 100% of the population is fully immunized and at least 24% having received a third dose—can reduce quarantine durations by up to 2 d, as well as substantially aid in the repression of outbreaks through serial testing. Our analysis highlights the paramount importance of maintaining high population immunity, preferably by booster uptake, and the role of quarantine and testing to control the spread of SARS CoV-2.

[PLoS ONE, 27 October 2022]

Initial efforts to mitigate the COVID-19 pandemic have relied heavily on non-pharmaceutical interventions (NPIs), including physical distancing, hand hygiene, and mask-wearing. However, an effective vaccine is essential to containing the spread of the virus. We developed a compartmental model to examine different vaccine strategies for controlling the spread of COVID-19. Our framework accounts for testing rates, test-turnaround times, and vaccination waning immunity. Using reported case data from the city of Toronto, Canada between Mar-Dec, 2020 we defined epidemic phases of infection using contact rates as well as the probability of transmission upon contact. We investigated the impact of vaccine distribution by comparing different permutations of waning immunity, vaccine coverage and efficacy throughout various stages of NPI’s relaxation in terms of cases and deaths. The basic reproduction number is also studied. We observed that widespread vaccine coverage substantially reduced the number of cases and deaths. Under phases with high transmission, an early or late reopening will result in new resurgence of the infection, even with the highest coverage. On the other hand, under phases with lower transmission, 60% of coverage is enough to prevent new infections. Our analysis of R0 showed that the basic reproduction number is reduced by decreasing the tests turnaround time and transmission in the household. While we found that household transmission can decrease following the introduction of a vaccine, public health efforts to reduce test turnaround times remain important for virus containment.

Citerank: (10) 679797Huaiping ZhuProfessor of mathematics at the Department of Mathematics and Statistics at York University, a York Research Chair (YRC Tier I) in Applied Mathematics, the Director of the Laboratory of Mathematical Parallel Systems at the York University (LAMPS), the Director of the Canadian Centre for Diseases Modelling (CCDM) and the Director of the One Health Modelling Network for Emerging Infections (OMNI-RÉUNIS). 10019D3ABAB, 679799Iain MoylesAssistant Professor in the Department of Mathematics and Statistics at York University. 10019D3ABAB, 679803Jacques BélairProfessor, Department of Mathematics and Statistics, Université de Montréal10019D3ABAB, 679805James WatmoughProfessor in the Department of Mathematics and Statistics at the University of New Brunswick.10019D3ABAB, 679817Julien ArinoProfessor and Faculty of Science Research Chair in Fundamental Science with the Department of Mathematics at the University of Manitoba.10019D3ABAB, 701037MfPH – Publications144B5ACA0, 701222OMNI – Publications144B5ACA0, 704045Covid-19859FDEF6, 714608Charting a FutureCharting a Future for Emerging Infectious Disease Modelling in Canada – April 2023 [1] 2794CAE1, 715328Nonpharmaceutical Interventions (NPIs)859FDEF6

[BMC Public Health, 15 July 2022]

Background: Since December 2020, public health agencies have implemented a variety of vaccination strategies to curb the spread of SARS-CoV-2, along with pre-existing Nonpharmaceutical Interventions (NPIs). Initial strategies focused on vaccinating the elderly to prevent hospitalizations and deaths, but with vaccines becoming available to the broader population, it became important to determine the optimal strategy to enable the safe lifting of NPIs while avoiding virus resurgence.

Methods: We extended the classic deterministic SIR compartmental disease-transmission model to simulate the lifting of NPIs under different vaccine rollout scenarios. Using case and vaccination data from Toronto, Canada between December 28, 2020, and May 19, 2021, we estimated transmission throughout past stages of NPI escalation/relaxation to compare the impact of lifting NPIs on different dates on cases, hospitalizations, and deaths, given varying degrees of vaccine coverages by 20-year age groups, accounting for waning immunity.

Results: We found that, once coverage among the elderly is high enough (80% with at least one dose), the main age groups to target are 20–39 and 40–59 years, wherein first-dose coverage of at least 70% by mid-June 2021 is needed to minimize the possibility of resurgence if NPIs are to be lifted in the summer. While a resurgence was observed for every scenario of NPI lifting, we also found that under an optimistic vaccination coverage (70% coverage by mid-June, along with postponing reopening from August 2021 to September 2021) can reduce case counts and severe outcomes by roughly 57% by December 31, 2021.

Conclusions: Our results suggest that focusing the vaccination strategy on the working-age population can curb the spread of SARS-CoV-2. However, even with high vaccination coverage in adults, increasing contacts and easing protective personal behaviours is not advisable since a resurgence is expected to occur, especially with an earlier reopening.

[Healthcare, 4 May 2023]

Mass vaccination is proving to be the most effective method of disease control, and several methods have been developed for the operation of mass vaccination clinics to administer vaccines safely and quickly. One such method is known as the hockey hub model, a relatively new method that involves isolating vaccine recipients in individual cubicles for the entire duration of the vaccination process. Healthcare staff move between the cubicles and administer vaccines. This allows for faster vaccine delivery and less recipient contact. In this paper we present a simulation tool which has been created to model the operation of a hockey hub clinic. This tool was developed using AnyLogic and simulates the process of individuals moving through a hockey hub vaccination clinic. To demonstrate this model, we simulate six scenarios comprising three different arrival rates with and without physical distancing. Findings demonstrate that the hockey hub method of vaccination clinic can function at a large capacity with minimal impact on wait times.

[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.

[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.

[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.

[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.

[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.

[Science Advances, 3 November 2023]

The seasonal influenza (flu) vaccine is designed to protect against those influenza viruses predicted to circulate during the upcoming flu season, but identifying which viruses are likely to circulate is challenging. We use features from phylogenetic trees reconstructed from hemagglutinin (HA) and neuraminidase (NA) sequences, together with a support vector machine, to predict future circulation. We obtain accuracies of 0.75 to 0.89 (AUC 0.83 to 0.91) over 2016–2020. We explore ways to select potential candidates for a seasonal vaccine and find that the machine learning model has a moderate ability to select strains that are close to future populations. However, consensus sequences among the most recent 3 years also do well at this task. We identify similar candidate strains to those proposed by the World Health Organization, suggesting that this approach can help inform vaccine strain selection.

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

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

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

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

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

[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.

[Biometrics, 10 August 2023]

We develop a proportional incidence model that estimates vaccine effectiveness (VE) at the population level using conditional likelihood for aggregated data. Our model assumes that the population counts of clinical outcomes for an infectious disease arise from a superposition of Poisson processes with different vaccination statuses. The intensity function in the model is calculated as the product of per capita incidence rate and the at-risk population size, both of which are time-dependent. We formulate a log-linear regression model with respect to the relative risk, defined as the ratio between the per capita incidence rates of vaccinated and unvaccinated individuals. In the regression analysis, we treat the baseline incidence rate as a nuisance parameter, similar to the Cox proportional hazard model in survival analysis. We then apply the proposed models and methods to age-stratified weekly counts of COVID-19–related hospital and ICU admissions among adults in Ontario, Canada. The data spanned from 2021 to February 2022, encompassing the Omicron era and the rollout of booster vaccine doses. We also discuss the limitations and confounding effects while advocating for the necessity of more comprehensive and up-to-date individual-level data that document the clinical outcomes and measure potential confounders.

[American Journal of Epidemiology, 9 March 2023]

Evidence from early observational studies suggested negative vaccine effectiveness (⁠VEff) for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. Since true VEff is unlikely to be negative, we explored how differences in contact among vaccinated persons (e.g., potentially from the implementation of vaccine mandates) could lead to observed negative VEff. Using a susceptible-exposed-infectious-recovered (SEIR) transmission model, we examined how vaccinated-contact heterogeneity, defined as an increase in the contact rate only between vaccinated individuals, interacted with 2 mechanisms of vaccine efficacy: vaccine efficacy against susceptibility (⁠VES) and vaccine efficacy against infectiousness (⁠VEI), to produce underestimated and in some cases, negative measurements of VEff. We found that vaccinated-contact heterogeneity led to negative estimates when VEI, and especially VES⁠, were low. Moreover, we determined that when contact heterogeneity was very high, VEff could still be underestimated given relatively high vaccine efficacies (0.7), although its effect on VEff was strongly reduced. We also found that this contact heterogeneity mechanism generated a signature temporal pattern: The largest underestimates and negative measurements of VEff occurred during epidemic growth. Overall, our research illustrates how vaccinated-contact heterogeneity could have feasibly produced negative measurements during the Omicron period and highlights its general ability to bias observational studies of VEff⁠.

[The Lancet Healthy Longevity, 14 July 2023]

Background: Older adults (aged ≥60 years) were prioritised for COVID-19 booster vaccination due to severe outcome risk, but the risk for this group is also affected by previous SARS-CoV-2 infection and vaccination. We estimated vaccine effectiveness against omicron-associated hospitalisation in older adults by previously documented infection, time since last immunological event, and age group.

Methods: This was a population-based test-negative case-control study done in Quebec, Canada, during BA.1 dominant (December, 2021, to March, 2022), BA.2 dominant (April to June, 2022), and BA.4/5 dominant (July to November, 2022) periods using provincial laboratory, immunisation, hospitalisation, and chronic disease surveillance databases. We included older adults (aged ≥60 years) with symptoms associated with COVID-19 who were tested for SARS-CoV-2 in acute-care hospitals. Cases were defined as patients who were hospitalised for COVID-19 within 14 days after testing positive; controls were patients who tested negative. Analyses spanned 3–14 months after last vaccine dose or previous infection. Logistic regression models compared COVID-19 hospitalisation risk by mRNA vaccine dose and previous infection versus unvaccinated and infection-naive participants.

Findings: Between Dec 26, 2021, and Nov 5, 2022, we included 174 819 specimens (82 870 [47·4%] from men and 91 949 [52·6%] from women; from 8455 cases and 166 364 controls), taken from 2951 cases and 48 724 controls in the BA.1 period; 1897 cases and 41 702 controls in the BA.2 period; and 3607 cases and 75 938 controls in the BA.4/5 period. In participants who were infection naive, vaccine effectiveness against hospitalisation improved with dose number, consistent with a shorter median time since last dose, but decreased with more recent omicron subvariants. Four-dose vaccine effectiveness was 96% (95% CI 93–98) during the BA.1 period, 84% (81–87) during the BA.2 period, and 68% (63–72) during the BA.4/5 period. Regardless of dose number (two to five doses) or timing since previous infection, hybrid protection was more than 90%, persisted for at least 6–8 months, and did not decline with age.

Interpretation: Older adults with both previous SARS-CoV-2 infection and two or more vaccine doses appear to be well protected for a prolonged period against hospitalisation due to omicron subvariants, including BA.4/5. Ensuring that older adults who are infection naive remain up to date with vaccination might reduce COVID-19 hospitalisations most efficiently.

[Human Vaccines & Immunotherapeutics, 8 June 2023]

Vaccine certificates have been implemented worldwide, aiming to promote vaccination rates and to reduce the spread of COVID-19. However, their use during the COVID-19 pandemic was controversial and has been criticized for infringing upon medical autonomy and individual rights. We administered a national online survey exploring social and demographic factors predicting the degree of public approval of vaccine certificates in Canada. We conducted a multivariate linear regression which revealed which factors were predictive of vaccine certificate acceptance in Canada. Self-reported minority status (p < .001), rurality (p < .001), political ideology (p < .001), age (p < .001), having children under 18 in the household (p < .001), education (p = .014), and income status (p = .034) were significant predictors of attitudes toward COVID-19 vaccine certificates. We observed the lowest vaccine-certificate approval among participants who: self-identify as a visible minority; live in rural areas; are politically conservative; are 18–34 years of age; have children under age 18 living in the household; have completed an apprenticeship or trades education; and those with an annual income between $100,000–$159,999. The present findings are valuable for their ability to inform the implementation of vaccine certificates during future pandemic scenarios which may require targeted communication between public health agencies and under-vaccinated populations.

[The Lancet Public Health, October 2023]

Background: Given the accumulating evidence that one-dose vaccination could provide high and sustained protection against human papillomavirus (HPV) infection and related diseases, we examined the population-level effectiveness and efficiency of one-dose HPV vaccination of girls compared with two-dose vaccination, using mathematical modelling.

Methods: In this mathematical modelling study, we used HPV-ADVISE LMIC, an individual-based transmission-dynamic model independently calibrated to four epidemiologically diverse low-income and middle-income countries (LMICs; India, Nigeria, Uganda, and Viet Nam). We parameterised and calibrated the model using sexual behaviour and epidemiological data identified from international population-based datasets and the literature. All base-case vaccination scenarios start in 2023 with the nonavalent vaccine and assumed 80% vaccination coverage with one or two doses. We assumed that two doses of vaccine provide 100% efficacy against vaccine-type infections and a lifelong duration of protection. We examined a non-inferior vaccination scenario for one dose compared with two doses, pessimistic scenarios of lower one-dose vaccine efficacy (85%) or a shorter duration of protection (ie, 20 or 30 years), and the effectiveness of a mitigation scenario in which schedules would switch from one dose to two doses. We also did sensitivity analyses by varying vaccination coverage. We used three outcomes: the relative reduction in cervical cancer incidence, the number of cervical cancers averted, and the number of vaccine doses needed to prevent one cervical cancer.

Findings: Assuming non-inferior vaccine characteristics for one dose compared with two doses, the model projections show that two-dose or one-dose routine vaccination of girls aged 9 years (with a multi-age cohort vaccination of girls aged 10–14 years) would avert 12·0 million (80% UI 9·5–14·5) cervical cancers in India, 4·7 million (3·4–5·8) in Nigeria, 2·3 million (1·9–2·6) in Uganda, and 0·4 million (0·2–0·5) in Viet Nam over 100 years. Under pessimistic assumptions of lower one-dose efficacy (85%) or a shorter duration of protection (ie, 30 years), one-dose routine vaccination would avert 69% (61–80) to 94% (92–96) of the cervical cancers averted with two-dose routine vaccination. However, when assuming a duration of protection of 20 years, one-dose routine vaccination would avert substantially fewer cervical cancers (ie, 35% [26–44] to 69% [65–71] of the cervical cancers averted with two-dose routine vaccination). A switch from one-dose to two-dose routine vaccination of girls aged 9 years, with a one-dose catch-up of girls aged 10–14 years, 5 years after the start of the vaccination programme, could mitigate potential losses in cervical cancer prevention from a short one-dose duration of protection (averting 92% [83–98] to 99% [97–100]) of the cervical cancers averted with two-dose routine vaccination). One-dose routine vaccination would result in fewer doses needed to prevent one cervical cancer than two-dose routine vaccination, even if the duration of protection is as low as 20 years. Finally, for countries with two-dose routine vaccination, adding one-dose multi-age cohort vaccination in the first year would provide similar benefits as a two-dose multi-age cohort vaccination, and would be more efficient even under the pessimistic assumptions of lower one-dose vaccine efficacy or duration of protection.

Interpretation: One-dose routine vaccination could avert most of the cervical cancers averted with two-dose vaccination while being more efficient, provided the duration of one-dose protection is greater than 20–30 years (depending on the LMIC). The doses saved by introducing one-dose routine vaccination could offer the opportunity to vaccinate girls before they age out of the vaccination window of 9–14 years and, potentially, to vaccinate boys or older age groups.

[The Journal of Infectious Diseases, 7 June 2022]

Background: Longer-term humoral responses to 2-dose coronavirus disease 2019 (COVID-19) vaccines remain incompletely characterized in people living with human immunodeficiency virus (HIV) (PLWH), as do initial responses to a third dose.

Methods: We measured antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, angiotensin-converting enzyme 2 (ACE2) displacement, and viral neutralization against wild-type and Omicron strains up to 6 months after 2-dose vaccination, and 1 month after the third dose, in 99 PLWH receiving suppressive antiretroviral therapy and 152 controls.

Results: Although humoral responses naturally decline after 2-dose vaccination, we found no evidence of lower antibody concentrations or faster rates of antibody decline in PLWH compared with controls after accounting for sociodemographic, health, and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after 2 doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post–third-dose humoral responses substantially exceeded post–second-dose levels, though Omicron-specific responses were consistently weaker than responses against wild-type virus. Nevertheless, post–third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post–third-dose responses.

Conclusion: PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after 2- and 3-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron

[Pediatrics, 3 March 2023]

OBJECTIVES: This study aimed to provide real-world evidence on coronavirus disease 2019 vaccine effectiveness (VE) against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years.

METHODS: We used the test-negative study design and linked provincial databases to estimate BNT162b2 vaccine effectiveness against symptomatic infection and severe outcomes caused by Omicron in children aged 5 to 11 years between January 2 and August 27, 2022 in Ontario. We used multivariable logistic regression to estimate VE by time since the latest dose, compared with unvaccinated children, and we evaluated VE by dosing interval.

RESULTS: We included 6284 test-positive cases and 8389 test-negative controls. VE against symptomatic infection declined from 24% (95% confidence interval [CI], 8% to 36%) 14 to 29 days after a first dose and 66% (95% CI, 60% to 71%) 7 to 29 days after 2 doses. VE was higher for children with dosing intervals of ≥56 days (57% [95% CI, 51% to 62%]) than 15 to 27 days (12% [95% CI, −11% to 30%]) and 28 to 41 days (38% [95% CI, 28% to 47%]), but appeared to wane over time for all dosing interval groups. VE against severe outcomes was 94% (95% CI, 57% to 99%) 7 to 29 days after 2 doses and declined to 57% (95%CI, −20% to 85%) after ≥120 days.

CONCLUSIONS: In children aged 5 to 11 years, 2 doses of BNT162b2 provide moderate protection against symptomatic Omicron infection within 4 months of vaccination and good protection against severe outcomes. Protection wanes more rapidly for infection than severe outcomes. Overall, longer dosing intervals confer higher protection against symptomatic infection, however protection decreases and becomes similar to shorter dosing interval starting 90 days after vaccination.

[International Journal of Infectious Diseases, 26 March 2023]

Since the emergence of the SARS-CoV-2 Omicron variant, multiple observational studies have reported negative vaccine effectiveness (VE) against infection, symptomatic infection, and even severity (hospitalization), potentially leading to an interpretation that vaccines were facilitating infection and disease. However, current observations of negative VE likely stem from the presence of various biases (e.g., exposure differences, testing differences). Although negative VE is more likely to arise when true biological efficacy is generally low and biases are large, positive VE measurements can also be subject to the same mechanisms of bias. In this perspective, we first outline the different mechanisms of bias that could lead to false-negative VE measurements and then discuss their ability to potentially influence other protection measurements. We conclude by discussing the use of suspected false-negative VE measurements as a signal to interrogate the estimates (quantitative bias analysis) and to discuss potential biases when communicating real-world immunity research.

[International Journal of Infectious Diseases, 24 March 2023]

Objectives: We aimed to estimate the rate of myocarditis after the messenger RNA (mRNA) COVID-19 booster vaccination by vaccine type, age, and sex.

Methods: We used data from the British Columbia COVID-19 Cohort, a population-based cohort surveillance platform. The exposure was a booster dose of an mRNA vaccine. The outcome was diagnosis of myocarditis during hospitalization or an emergency department visit within 7-21 days of booster vaccination.

Results: The overall rate of myocarditis was lower for the booster dose (6.41, 95% confidence interval [CI]: 3.50-10.75) than the second dose (17.97, 95% CI: 13.78-23.04); (Rate ratiobooster vs dose-2 = 0.34, 95% CI: 0.17-0.61). This difference was more apparent for the mRNA-1273 vaccine type. After the second dose, the myocarditis rate in males was significantly lower for BNT162b2 than mRNA-1273 overall and among those aged 18-39 years. In contrast, after the booster dose, no significant differences between myocarditis and vaccine type was observed overall or within the specific age groups among males or females.

Conclusion: Myocarditis after mRNA COVID-19 vaccines is a rare event. A lower absolute risk of myocarditis was observed after a booster dose of mRNA vaccine than the primary series second dose.

[Vaccine, 29 September 2023]

Background: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults.

Methods: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI).

Results: Of 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%–51.1%) for naTIV and 53.5% (42.8%–62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%–66.8%) for aTIV and 44.8% (39.1%–50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61–0.92), demonstrating statistically significant benefit favoring aTIV.

Conclusions: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

[Open Forum Infectious Diseases, 9 February 2023]

Background: Longer-term immune response data after 3 doses of coronavirus disease 2019 (COVID-19) mRNA vaccine remain limited, particularly among older adults and after Omicron breakthrough infection.

Methods: We quantified wild-type- and Omicron-specific serum immunoglobulin (Ig)G levels, angiotensin-converting enzyme 2 displacement activities, and live virus neutralization up to 6 months after third dose in 116 adults aged 24–98 years who remained COVID-19 naive or experienced their first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during this time.

Results: Among the 78 participants who remained COVID-19 naive throughout follow up, wild-type- and Omicron-BA.1-specific IgG concentrations were comparable between younger and older adults, although BA.1-specific responses were consistently significantly lower than wild-type-specific responses in both groups. Wild-type- and BA.1-specific IgG concentrations declined at similar rates in COVID-19-naive younger and older adults, with median half-lives ranging from 69 to 78 days. Antiviral antibody functions declined substantially over time in COVID-19-naive individuals, particularly in older adults: by 6 months, BA.1-specific neutralization was undetectable in 96% of older adults, versus 56% of younger adults. Severe acute respiratory syndrome coronavirus 2 infection, experienced by 38 participants, boosted IgG levels and neutralization above those induced by vaccination alone. Nevertheless, BA.1-specific neutralization remained significantly lower than wild-type, with BA.5-specific neutralization lower still. Higher Omicron BA.1-specific neutralization 1 month after third dose was an independent correlate of lower SARS-CoV-2 infection risk.

Conclusions: Results underscore the immune benefits of the third COVID-19 mRNA vaccine dose in adults of all ages and identify vaccine-induced Omicron-specific neutralization as a correlate of protective immunity. Systemic antibody responses and functions however, particularly Omicron-specific neutralization, decline rapidly in COVID-19-naive individuals, particularly in older adults, supporting the need for additional booster doses.

[Clinical Infectious Diseases, 17 August 2022]

Background: A major goal of coronavirus disease 2019 (COVID-19) vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of messenger RNA (mRNA) and ChAdOx1 COVID-19 vaccines against severe outcomes in 4 Canadian provinces between December 2020 and September 2021.

Methods: We conducted this multiprovincial, retrospective, test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random-effects models.

Results: We included 2 508 296 tested participants, with 31 776 COVID-19 hospitalizations and 5842 deaths. Vaccine effectiveness was 83% after a first dose and 98% after a second dose against both hospitalization and death (separately). Against severe outcomes, effectiveness was 87% (95% confidence interval [CI], 71%–94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95% CI, 96%–99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95% CI, 75%–94%) ≥56 days after a first dose, increasing to 97% (95% CI, 91%–99%) ≥56 days after a second dose. Lower 1-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules and against Alpha, Gamma, and Delta variants.

Conclusions: Two doses of mRNA or ChAdOx1 vaccine provide excellent protection against severe outcomes.

[medRxiv, 10 June 2023]

Background: Vaccine homophily describes non-heterogeneous vaccine uptake within contact networks. This study was performed to determine observable patterns of vaccine homophily, associations between vaccine homophily, self-reported vaccination, COVID-19 prevention behaviours, contact network size, and self-reported COVID-19, as well as the impact of vaccine homophily on disease transmission within and between vaccination groups under conditions of high and low vaccine efficacy.

Methods: Residents of British Columbia, Canada, aged ≥16 years, were recruited via online advertisements between February and March 2022, and provided information about vaccination status, perceived vaccination status of household and non-household contacts, compliance with COVID-19 prevention guidelines, and history of COVID-19. A deterministic mathematical model was used to assess transmission dynamics between vaccine status groups under conditions of high and low vaccine efficacy.

Results: Vaccine homophily was observed among the 1304 respondents, but was lower among those with fewer doses (p<0.0001). Unvaccinated individuals had larger contact networks (p<0.0001), were more likely to report prior COVID-19 (p<0.0001), and reported lower compliance with COVID-19 prevention guidelines (p<0.0001). Mathematical modelling showed that vaccine homophily plays a considerable role in epidemic growth under conditions of high and low vaccine efficacy. Further, vaccine homophily contributes to a high force of infection among unvaccinated individuals under conditions of high vaccine efficacy, as well as elevated force of infection from unvaccinated to vaccinated individuals under conditions of low vaccine efficacy.

Interpretation: The uneven uptake of COVID-19 vaccines and the nature of the contact network in the population play important roles in shaping COVID-19 transmission dynamics.

[medRxiv, 30 July 2023]

Two different epidemiological models of vaccination are commonly used in dynamical modeling studies. The leaky vaccination model assumes that all vaccinated individuals experience a reduced force of infection by the same amount. The polarized vaccination model assumes that some fraction of vaccinated individuals are completely protected, while the remaining fraction remains completely susceptible; this seemingly extreme assumption causes the polarized model to always predict lower final epidemic size than the leaky model under the same vaccine efficacy. However, the leaky model also makes an implicit, unrealistic assumption: vaccinated individuals who are exposed to infection but not infected remain just as susceptible as they were prior to exposures (i.e., independent of previous exposures). To resolve the independence assumption, we introduce an immune boosting mechanism, through which vaccinated, yet susceptible, individuals can gain protection without developing a transmissible infection. The boosting model further predicts identical epidemic dynamics as the polarized vaccination model, thereby bridging the differences between two models. We further develop a generalized vaccination model to explore how the assumptions of immunity affect epidemic dynamics and estimates of vaccine effectiveness.

[Journal of Mathematical Biology, 23 June 2022]

Various vaccines have been approved for use to combat COVID-19 that offer imperfect immunity and could furthermore wane over time. We analyze the effect of vaccination in an SLIARS model with demography by adding a compartment for vaccinated individuals and considering disease-induced death, imperfect and waning vaccination protection as well as waning infections-acquired immunity. When analyzed as systems of ordinary differential equations, the model is proven to admit a backward bifurcation. A continuous time Markov chain (CTMC) version of the model is simulated numerically and compared to the results of branching process approximations. While the CTMC model detects the presence of the backward bifurcation, the branching process approximation does not. The special case of an SVIRS model is shown to have the same properties.

[SSRN, 3 September 2021]

Background: After the start of the COVID-19 pandemic and its spread across the world, countries have adopted containment measures to stop its transmission, limit fatalities and relieve hospitals from strain and overwhelming imposed by the virus. Many countries implemented social distancing and lockdown strategies that negatively impacted their economies and the psychological wellbeing of their citizens, even though they contributed to saving lives. Recently approved and available, COVID-19 vaccines can provide a really viable and sustainable option for controlling the pandemic. However, their uptake represents a global challenge, due to vaccine hesitancy logistic-organizational hurdles that have made its distribution stagnant in several developed countries despite several appeal by the media, policy- and decision-makers, and community leaders. Vaccine distribution is a concern also in developing countries, where there is scarcity of doses.

Objective: To set up a metric to assess vaccination uptake and identify national socio-economic factors influencing this indicator.

Methods: We conducted a cross-country study. We first estimated the vaccination uptake rate across countries by fitting a logistic model to reported daily case numbers. Using the uptake rate, we estimated the vaccine roll-out index. Next, we used Random Forest, an “off-the-shelf” machine learning algorithm, to study the association between vaccination uptake rate and socio-economic factors.

Results: We found that the mean vaccine roll-out index is 0.016 (standard deviation 0.016), with a range between 0.0001 (Haiti) and 0.0829 (Mongolia). The top four factors associated with vaccine roll-out index are the median per capita income, human development index, percentage of individuals who have used the internet in the last three months, and health expenditure per capita.

Conclusion: The still ongoing COVID-19 pandemic has shed light on the chronic inequality in global health systems. The disparity in vaccine adoption across low- and high-income countries is a global public health challenge. We must pave the way for a universal access to vaccines and other approved treatments, regardless of demographic structures and underlying health conditions. Income disparity remains, instead, an important cause of vaccine inequity, and the tendency toward "vaccine nationalism" and “vaccine apartheid” restricts the functioning of the global vaccine allocation framework and, thus, the ending of the pandemic. Stronger mechanisms are needed to foster countries' political willingness to promote vaccine and drug access equity in a globalized society, where future pandemics and other global health rises can be anticipated.

[npj Digital Medicine, 25 May 2023]

Chatbots have become an increasingly popular tool in the field of health services and communications. Despite chatbots’ significance amid the COVID-19 pandemic, few studies have performed a rigorous evaluation of the effectiveness of chatbots in improving vaccine confidence and acceptance. In Thailand, Hong Kong, and Singapore, from February 11th to June 30th, 2022, we conducted multisite randomised controlled trials (RCT) on 2,045 adult guardians of children and seniors who were unvaccinated or had delayed vaccinations. After a week of using COVID-19 vaccine chatbots, the differences in vaccine confidence and acceptance were compared between the intervention and control groups. Compared to non-users, fewer chatbot users reported decreased confidence in vaccine effectiveness in the Thailand child group [Intervention: 4.3 % vs. Control: 17%, P = 0.023]. However, more chatbot users reported decreased vaccine acceptance [26% vs. 12%, P = 0.028] in Hong Kong child group and decreased vaccine confidence in safety [29% vs. 10%, P = 0.041] in Singapore child group. There was no statistically significant change in vaccine confidence or acceptance in the Hong Kong senior group. Employing the RE-AIM framework, process evaluation indicated strong acceptance and implementation support for vaccine chatbots from stakeholders, with high levels of sustainability and scalability. This multisite, parallel RCT study on vaccine chatbots found mixed success in improving vaccine confidence and acceptance among unvaccinated Asian subpopulations. Further studies that link chatbot usage and real-world vaccine uptake are needed to augment evidence for employing vaccine chatbots to advance vaccine confidence and acceptance.

[Research Square, 27 February 2023]

Background: The success of vaccination programs often depends on the effectiveness of the vaccine messages, particularly during emergencies such as the COVID-19 pandemic. The current suboptimal uptake of COVID-19 vaccines across many parts of the world highlights the tremendous challenges in overcoming vaccine hesitancy and refusal even in the context of a world-devastating pandemic.

Methods: We conducted a randomized controlled trial in Hong Kong to evaluate the impact of seven vaccine messages on COVID-19 vaccine uptake (with the government slogan as the control). The participants included 127,000 individuals who googled COVID-19-related information during July-October 2021.

Results: The impact of vaccine messages on uptake varied substantially over time and among different groups of users. For example, the message that emphasized the indirect protection of vaccination on family members (i) increased overall uptake by 30% (6-59%) in July but had no effect afterwards for English language users; and (ii) had no effect on overall uptake for Chinese language users throughout the study. Such volatility and heterogeneity in message effectiveness highlight the limitations of one-size-fits-all and static vaccine communication.

Conclusions: Epidemic nowcasting should include real-time monitoring of vaccine hesitancy and message effectiveness, in order to adapt messaging appropriately. This dynamic dimension of surveillance has so far been underinvested.

[Journal of Theoretical Biology, 21 February 2023]

Current persistent outbreak of COVID-19 is triggering a series of collective responses to avoid infection. To further clarify the impact mechanism of adaptive protection behavior and vaccination, we developed a new transmission model via a delay differential system, which parameterized the roles of adaptive behaviors and vaccination, and allowed to simulate the dynamic infection process among people. By validating the model with surveillance data during March 2020 and October 2021 in America, India, South Africa, Philippines, Brazil, UK, Spain and Germany, we quantified the protection effect of adaptive behaviors by different forms of activity function. The modeling results indicated that (1) the adaptive activity function can be used as a good indicator for fitting the intervention outcome, which exhibited short-term awareness in these countries, and it could reduce the total human infections by 3.68, 26.16, 15.23, 4.23, 7.26, 1.65, 5.51 and 7.07 times, compared with the reporting; (2) for complete prevention, the average proportions of people with immunity should be larger than 90%, 92%, 86%, 71%, 92%, 84%, 82% and 76% with adaptive protection behaviors, or 91%, 97%, 94%, 77%, 92%, 88%, 85% and 90% without protection behaviors; and (3) the required proportion of humans being vaccinated is a sub-linear decreasing function of vaccine efficiency, with small heterogeneity in different countries. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”.

Citerank: (9) 701037MfPH – Publications144B5ACA0, 701624Zahra MohammadiPostdoctoral Fellow, Mathematics for Public health, Fields Institute, Department of Mathematics and Statistics, University of Guelph, Memorial University of Newfoundland.10019D3ABAB, 703963Mobility859FDEF6, 704036Immunology859FDEF6, 704045Covid-19859FDEF6, 704045Covid-19859FDEF6, 715328Nonpharmaceutical Interventions (NPIs)859FDEF6, 715419Edward Thommes Edward W. Thommes is an Adjunct Professor of Mathematics at the University of Guelph and at York University. He is a Global Modeling Lead in the Modeling, Epidemiology and Data Science (MEDS) team of Sanofi Vaccines, an Affiliate Researcher in the Waterloo Institute for Complexity and Innovation (WICI), and a member of the Strategic Advisory Committee for the Mathematics for Public Health program at the Fields Institute.10019D3ABAB, 715762Monica CojocaruProfessor in the Mathematics & Statistics Department at the University of Guelph. 10019D3ABAB

[BMC Public Health, 22 August 2022]

Background: The outbreak of Coronavirus disease, which originated in Wuhan, China in 2019, has affected the lives of billions of people globally. Throughout 2020, the reproduction number of COVID-19 was widely used by decision-makers to explain their strategies to control the pandemic.

Methods: In this work, we deduce and analyze both initial and effective reproduction numbers for 12 diverse world regions between February and December of 2020. We consider mobility reductions, mask wearing and compliance with masks, mask efficacy values alongside other non-pharmaceutical interventions (NPIs) in each region to get further insights in how each of the above factored into each region’s SARS-COV-2 transmission dynamic.

Results: We quantify in each region the following reductions in the observed effective reproduction numbers of the pandemic: i) reduction due to decrease in mobility (as captured in Google mobility reports); ii) reduction due to mask wearing and mask compliance; iii) reduction due to other NPI’s, over and above the ones identified in i) and ii).

Conclusion: In most cases mobility reduction coming from nationwide lockdown measures has helped stave off the initial wave in countries who took these types of measures. Beyond the first waves, mask mandates and compliance, together with social-distancing measures (which we refer to as other NPI’s) have allowed some control of subsequent disease spread. The methodology we propose here is novel and can be applied to other respiratory diseases such as influenza or RSV.

[BMC Medicine, 23 November 2022]

Background: Diagnostic testing has been pivotal in detecting SARS-CoV-2 infections and reducing transmission through the isolation of positive cases. We quantified the value of implementing frequent, rapid antigen (RA) testing in the workplace to identify screening programs that are cost-effective.

Methods: To project the number of cases, hospitalizations, and deaths under alternative screening programs, we adapted an agent-based model of COVID-19 transmission and parameterized it with the demographics of Ontario, Canada, incorporating vaccination and waning of immunity. Taking into account healthcare costs and productivity losses associated with each program, we calculated the incremental cost-effectiveness ratio (ICER) with quality-adjusted life year (QALY) as the measure of effect. Considering RT-PCR testing of only severe cases as the baseline scenario, we estimated the incremental net monetary benefits (iNMB) of the screening programs with varying durations and initiation times, as well as different booster coverages of working adults.

Results: Assuming a willingness-to-pay threshold of CDN$30,000 per QALY loss averted, twice weekly workplace screening was cost-effective only if the program started early during a surge. In most scenarios, the iNMB of RA screening without a confirmatory RT-PCR or RA test was comparable or higher than the iNMB for programs with a confirmatory test for RA-positive cases. When the program started early with a duration of at least 16 weeks and no confirmatory testing, the iNMB exceeded CDN$1.1 million per 100,000 population. Increasing booster coverage of working adults improved the iNMB of RA screening.

Conclusions: Our findings indicate that frequent RA testing starting very early in a surge, without a confirmatory test, is a preferred screening program for the detection of asymptomatic infections in workplaces.

Citerank: (11) 679761Caroline ColijnDr. Caroline Colijn works at the interface of mathematics, evolution, infection and public health, and leads the MAGPIE research group. She joined SFU's Mathematics Department in 2018 as a Canada 150 Research Chair in Mathematics for Infection, Evolution and Public Health. She has broad interests in applications of mathematics to questions in evolution and public health, and was a founding member of Imperial College London's Centre for the Mathematics of Precision Healthcare.10019D3ABAB, 679770Christopher McCabeDr. Christopher McCabe is the CEO and Executive Director of the Institute of Health Economics (IHE).10019D3ABAB, 679862Paul TupperProfessor in the Department of Mathematics at Simon Fraser University.10019D3ABAB, 685420Hospitals16289D5D4, 686720Erin KirwinErin Kirwin (she/her) is a Health Economist at the Institute of Health Economics (IHE) in Alberta, Canada. She holds a Bachelor of Arts (Honours) in Economics and International Development Studies from McGill University and a Master of Arts in Economics from the University of Alberta. Prior to joining the IHE, Erin was the Manager of Advanced Analytics at Alberta Health. Erin is a PhD candidate at the University of Manchester.10019D3ABAB, 701020CANMOD – PublicationsPublications by CANMOD Members144B5ACA0, 704045Covid-19859FDEF6, 708794Health economics859FDEF6, 714608Charting a FutureCharting a Future for Emerging Infectious Disease Modelling in Canada – April 2023 [1] 2794CAE1, 715454Workforce impact859FDEF6, 715952Long covid859FDEF6

[PLOS Global Public Health, 13 October 2021]

In vaccination campaigns against COVID-19, many jurisdictions are using age-based rollout strategies, reflecting the much higher risk of severe outcomes of infection in older groups. In the wake of growing evidence that approved vaccines are effective at preventing not only adverse outcomes, but also infection, we show that such strategies are less effective than strategies that prioritize essential workers. This conclusion holds across numerous outcomes, including cases, hospitalizations, Long COVID (cases with symptoms lasting longer than 28 days), deaths and net monetary benefit. Our analysis holds in regions where the vaccine supply is limited, and rollout is prolonged for several months. In such a setting with a population of 5M, we estimate that vaccinating essential workers sooner prevents over 200,000 infections, over 600 deaths, and produces a net monetary benefit of over $500M.

[BMJ Global Health, 12 December 2023]

Introduction: Fragmentation in immunisation reporting systems pose challenges in measuring vaccine coverage for First Nations children in Canada. Some Nations have entered into data-sharing agreements with the province of Alberta’s health ministry, enabling novel opportunities to calculate coverage.

Methods: Partnering with a First Nations community in Alberta, this retrospective cohort study calculated routine childhood vaccine coverage. Administrative data for vaccines delivered within and outside the community were linked to calculate partial and complete immunisation coverage in 2013–2019 at ages 2 and 7 years for children living in the community. We also compared vaccine coverage each year for (a) children who were and were not continuous community residents and (b) children who received or not their first vaccine at the on-reserve community health centre. We also calculated the mean complete coverage across all study years with 95% CIs.

Results: For most vaccines, coverage was higher (p<0.05) at ages 2 and 7 years for children that received their first vaccine at the First Nations health centre, compared with those who received their first dose elsewhere. For example, for pneumococcal vaccine, the mean level of complete coverage in 2-year-olds was 55.7% (52.5%–58.8%) for those who received their first vaccine in the community, compared with 33.3% (29.4%–37.3%) for those who did not; it was also higher at 7 years (75.6%, 72.7%–78.5%, compared with 55.5%, 49.7%–61.3%).

Conclusion: Initiating the vaccine series at the on-reserve community health centre had a positive impact on coverage. The ability to measure accurate coverage through data-sharing agreements and vaccine record linkage will support First Nations communities in identifying individual and community immunity. The findings also support the transfer of health funding and service delivery to First Nations to improve childhood immunisation uptake.

[Vaccine, 6 February 2024]

Background: Social networks have an important impact on our health behaviours, including vaccination. People’s vaccination beliefs tend to mirror those of their social network. As social networks are homogenous in many ways, we sought to determine in the context of COVID-19 which factors were most predictive of belonging to a mostly vaccinated or unvaccinated social group.

Methods: We conducted a cross-sectional survey among Canadian residents in November and December 2021. Participants were asked about the vaccination status of their social networks their beliefs relating to COVID-19, and various sociodemographic factors. Respondents were split into three groups based on social network vaccination: low-, medium-, and high-risk. Chi-squared tests tested associations between factors and risk groups, and an ordinal logistic model was created to determine their direction and strength.

Results: Most respondents (81.1 %) were classified as low risk (i.e., a mostly vaccinated social network) and few respondents (3.7 %) were classified as high-risk (i.e., an unvaccinated social group). Both the chi-square test (29.2 % difference between the low- and high- risk groups [1.8 % vs. 31.0 %], p < 0.001) and the ordinal logistic model (odds ratio between the low- and high-risk groups: 14.45, p < 0.01) found that respondents’ perceptions of COVID-19 as a “not at all serious” risk to Canadians was the most powerful predictor of belonging to a predominantly unvaccinated social circle. The model also found that those in mostly unvaccinated social circles also more often reported severe COVID-19 symptoms (odds ratio between the low- and high-risk groups: 2.26, p < 0.05).

Conclusion: Perception of COVID-19 as a threat to others may signal communities with lower vaccination coverage and higher risk of severe outcomes. This may have implications for strategies to improve public outreach, messaging, and planning for downstream consequences of low intervention uptake.

[BMC Infectious Diseases, 15 January 2024]

Background and objectives: Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC).

Methods: We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults < 25 years between November 2020-May 2021 and phase 2 enrolled children < 10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity.

Results: A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups).

Conclusions: SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms.

[PLoS ONE, 4 April 2024]

Background: We previously demonstrated that when vaccines prevent infection, the dynamics of mixing between vaccinated and unvaccinated sub-populations is such that use of imperfect vaccines markedly decreases risk for vaccinated people, and for the population overall. Risks to vaccinated people accrue disproportionately from contact with unvaccinated people. In the context of the emergence of Omicron SARS-CoV-2 and evolving understanding of SARS-CoV-2 epidemiology, we updated our analysis to evaluate whether our earlier conclusions remained valid.

Methods: We modified a previously published Susceptible-Infectious-Recovered (SIR) compartmental model of SARS-CoV-2 with two connected sub-populations: vaccinated and unvaccinated, with non-random mixing between groups. Our expanded model incorporates diminished vaccine efficacy for preventing infection with the emergence of Omicron SARS-CoV-2 variants, waning immunity, the impact of prior immune experience on infectivity, “hybrid” effects of infection in previously vaccinated individuals, and booster vaccination. We evaluated the dynamics of an epidemic within each subgroup and in the overall population over a 10-year time horizon.

Results: Even with vaccine efficacy as low as 20%, and in the presence of waning immunity, the incidence of COVID-19 in the vaccinated subpopulation was lower than that among the unvaccinated population across the full 10-year time horizon. The cumulative risk of infection was 3–4 fold higher among unvaccinated people than among vaccinated people, and unvaccinated people contributed to infection risk among vaccinated individuals at twice the rate that would have been expected based on the frequency of contacts. These findings were robust across a range of assumptions around the rate of waning immunity, the impact of “hybrid immunity”, frequency of boosting, and the impact of prior infection on infectivity in unvaccinated people.

Interpretation: Although the emergence of the Omicron variants of SARS-CoV-2 has diminished the protective effects of vaccination against infection with SARS-CoV-2, updating our earlier model to incorporate loss of immunity, diminished vaccine efficacy and a longer time horizon, does not qualitatively change our earlier conclusions. Vaccination against SARS-CoV-2 continues to diminish the risk of infection among vaccinated people and in the population as a whole. By contrast, the risk of infection among vaccinated people accrues disproportionately from contact with unvaccinated people.