Examining the effects of voluntary avoidance behaviour and policy-mediated behaviour change on the dynamics of SARS-CoV-2: A mathematical model.

Background: Throughout the SARS-CoV-2 pandemic, policymakers have had to navigate between recommending voluntary behaviour change and policy-driven behaviour change to mitigate the impact of the virus. While individuals will voluntarily engage in self-protective behaviour when there is an increasing infectious disease risk, the extent to which this occurs and its impact on an epidemic is not known. Methods: This paper describes a deterministic disease transmission model exploring the impact of individual avoidance behaviour and policy-mediated avoidance behaviour on epidemic outcomes during the second wave of SARS-CoV-2 infections in Ontario, Canada (September 1, 2020 to February 28, 2021). The model incorporates an information feedback function based on empirically derived behaviour data describing the degree to which avoidance behaviour changed in response to the number of new daily cases COVID-19. Results: Voluntary avoidance behaviour alone was estimated to reduce the final attack rate by 23.1%, the total number of hospitalizations by 26.2%, and cumulative deaths by 27.5% over 6 months compared to a counterfactual scenario in which there were no interventions or avoidance behaviour. A provincial shutdown order issued on December 26, 2020 was estimated to reduce the final attack rate by 66.7%, the total number of hospitalizations by 66.8%, and the total number of deaths by 67.2% compared to the counterfactual scenario. Conclusion: Given the dynamics of SARS-CoV-2 in a pre-vaccine era, individual avoidance behaviour in the absence of government action would have resulted in a moderate reduction in disease however, it would not have been sufficient to entirely mitigate transmission and the associated risk to the population in Ontario. Government action during the second wave of the COVID-19 pandemic in Ontario reduced infections, protected hospital capacity, and saved lives.

Impact of immune evasion, waning and boosting on dynamics of population mixing between a vaccinated majority and unvaccinated minority.

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.

Impact of community mask mandates on SARS-CoV-2 transmission in Ontario after adjustment for differential testing by age and sex.

Mask use for prevention of respiratory infectious disease transmission is not new but has proven controversial during the SARS-CoV-2 pandemic. In Ontario, Canada, irregular regional introduction of community mask mandates in 2020 created a quasi-experiment useful for evaluating the impact of such mandates; however, Ontario SARS-CoV-2 case counts were likely biased by testing focused on long-term care facilities and healthcare workers. We developed a regression-based method that allowed us to adjust cases for under-testing by age and gender. We evaluated mask mandate effects using count-based regression models with either unadjusted cases, or testing-adjusted case counts, as dependent variables. Models were used to estimate mask mandate effectiveness, and the fraction of SARS-CoV-2 cases, severe outcomes, and costs, averted by mask mandates. Models using unadjusted cases as dependent variables identified modest protective effects of mask mandates (range 31-42%), with variable statistical significance. Mask mandate effectiveness in models predicting test-adjusted case counts was higher, ranging from 49% (95% CI 44-53%) to 76% (95% CI 57-86%). The prevented fraction associated with mask mandates was 46% (95% CI 41-51%), with 290,000 clinical cases, 3,008 deaths, and loss of 29,038 quality-adjusted life years averted from 2020 June to December, representing $CDN 610 million in economic wealth. Under-testing in younger individuals biases estimates of SARS-CoV-2 infection risk and obscures the impact of public health preventive measures. After adjustment for under-testing, mask mandates emerged as highly effective. Community masking saved substantial numbers of lives, and prevented economic costs, during the SARS-CoV-2 pandemic in Ontario, Canada.

Vaccine effectiveness against hospitalization among adolescent and pediatric SARS-CoV-2 cases between May 2021 and January 2022 in Ontario, Canada: A retrospective cohort study.

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.

Estimating the test-adjusted incidence of Chlamydia trachomatis infections identified through Public Health Ontario Laboratories in Peel region, Ontario, 2010-2018: a population-based study.

BACKGROUND: Public health guidelines for chlamydia testing are not sex specific, but young females test at a disproportionally higher rate than males and other age groups. This study aims to describe testing trends across age and sex subgroups, then estimate a test-adjusted incidence of chlamydia in these subgroups to identify gaps in current testing practices. METHODS: We used a population-based study to examine observed chlamydia rates by age and sex subgroups: 15-19 years, 20-29 years, 30-39 years and older than 40 years. The study included diagnostic test results recorded by Public Health Ontario Laboratories between Jan. 1, 2010, and Dec. 31, 2018, for individuals living in Peel region, Ontario. We then employed meta-regression models as a method of standardization to estimate the effect of sex and age on standardized morbidity ratio, testing ratio and test positivity, then calculate a test-adjusted incidence of chlamydia for each subgroup. RESULTS: Over the study period, infection, testing and test positivity varied across age and sex subgroups. Observed incidence and testing were highest in females aged 20-29 years, whereas males had the highest standardized test positivity across all age groups. After estimating test-adjusted incidence for each age-sex subgroup, males in the 15-19-year and 30-39-year age groups had an increase in incidence of 60.2% and 9.7%, respectively, compared with the observed incidence. INTERPRETATION: We found that estimated test-adjusted incidence was higher than observed incidence in males aged 15-19 years and 30-39 years. This suggests that infections in males are likely being missed owing to differential testing, and this may be contributing to the persistent increase in reported cases in Canada. Public health programming that targets males, especially in high-risk settings and communities, and use of innovative partner notification methods could be critical to curbing overall rates of chlamydia.

Severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Pregnancy in Ontario: A Matched Cohort Analysis.

BACKGROUND: Pregnancy represents a physiological state associated with increased vulnerability to severe outcomes from infectious diseases, both for the pregnant person and developing infant. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than nonpregnant people to accept vaccination. METHODS: We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy using a population-based SARS-CoV-2 case file from Ontario, Canada. Because of varying propensity to receive vaccination, and changes in dominant circulating viral strains over time, a time-matched cohort study was performed to evaluate the relative risk of severe illness in pregnant women with SARS-CoV-2 compared to other SARS-CoV-2 infected women of childbearing age (10-49 years old). Risk of severe SARS-CoV-2 outcomes was evaluated in pregnant women and time-matched nonpregnant controls using multivariable conditional logistic regression. RESULTS: Compared with the rest of the population, nonpregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio, 1.28), whereas risk of infection was reduced among pregnant women (standardized morbidity ratio, 0.43). After adjustment for confounding, pregnant women had a markedly elevated risk of hospitalization (adjusted odds ratio, 4.96; 95% confidence interval, 3.86-6.37) and intensive care unit admission (adjusted odds ratio, 6.58; 95% confidence interval, 3.29-13.18). The relative increase in hospitalization risk associated with pregnancy was greater in women without comorbidities than in those with comorbidities (P for heterogeneity, .004). CONCLUSIONS: Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favors SARS-CoV-2 vaccination in pregnant women.

Relative Virulence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Among Vaccinated and Unvaccinated Individuals Hospitalized With SARS-CoV-2.

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.

Quantifying the economic gains associated with COVID-19 vaccination in the Canadian population: A cost-benefit analysis.

Background: Vaccination has been a key part of Canada's coronavirus disease 2019 (COVID-19) pandemic response. Although the clinical benefits of vaccination are clear, an understanding of the population-level benefits of vaccination relative to the programmatic costs is of value. The objective of this article is to quantify the economic impact of COVID-19 vaccination in the Canadian population between December 2020 and March 2022. Methods: We conducted a model-based cost-benefit analysis of Canada's COVID-19 vaccination program. We used an epidemiological model to estimate the number of COVID-19 symptomatic cases, hospitalizations, post-COVID condition (PCC) cases, and deaths in the presence and absence of vaccination. Median, lower and upper 95% credible interval (95% CrI) outcome values from 100 model simulations were used to estimate the direct and indirect costs of illness, including the value of health. We used a societal perspective and a 1.5% discount rate. Results: We estimated that the costs of the vaccination program were far outweighed by the savings associated with averted infections and associated downstream consequences. Vaccination increased the net benefit by CAD $298.1 billion (95% CrI: 27.2-494.6) compared to the no vaccination counterfactual. The largest benefits were due to averted premature mortality, resulting in an estimated $222.0 billion (95% CrI: 31.2-379.0) benefit. Conclusion: Our model-based economic evaluation provides a retrospective assessment of COVID-19 vaccination during the first 16 months of the program in Canada and suggests that it was welfare-improving, considering the decreased hospitalizations and use of healthcare resources, deaths averted and lower morbidity from conditions such as PCC.

Pandemic fatigue or enduring precautionary behaviours? Canadians' long-term response to COVID-19 public health measures.

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

Impact of population mixing between vaccinated and unvaccinated subpopulations on infectious disease dynamics: implications for SARS-CoV-2 transmission.

BACKGROUND: The speed of vaccine development has been a singular achievement during the COVID-19 pandemic, although uptake has not been universal. Vaccine opponents often frame their opposition in terms of the rights of the unvaccinated. We sought to explore the impact of mixing of vaccinated and unvaccinated populations on risk of SARS-CoV-2 infection among vaccinated people. METHODS: We constructed a simple susceptible-infectious-recovered compartmental model of a respiratory infectious disease with 2 connected subpopulations: people who were vaccinated and those who were unvaccinated. We simulated a spectrum of patterns of mixing between vaccinated and unvaccinated groups that ranged from random mixing to complete like-with-like mixing (complete assortativity), in which people have contact exclusively with others with the same vaccination status. We evaluated the dynamics of an epidemic within each subgroup and in the population as a whole. RESULTS: We found that the risk of infection was markedly higher among unvaccinated people than among vaccinated people under all mixing assumptions. The contact-adjusted contribution of unvaccinated people to infection risk was disproportionate, with unvaccinated people contributing to infections among those who were vaccinated at a rate higher than would have been expected based on contact numbers alone. We found that as like-with-like mixing increased, attack rates among vaccinated people decreased from 15% to 10% (and increased from 62% to 79% among unvaccinated people), but the contact-adjusted contribution to risk among vaccinated people derived from contact with unvaccinated people increased. INTERPRETATION: Although risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to people who are unvaccinated, their choices affect risk of viral infection among those who are vaccinated in a manner that is disproportionate to the portion of unvaccinated people in the population.

Sporadic SARS-CoV-2 cases at the neighbourhood level in Toronto, Ontario, 2020: a spatial analysis of the early pandemic period.

BACKGROUND: As the largest city in Canada, Toronto has played an important role in the dynamics of SARS-CoV-2 transmission in Ontario, and the burden of disease across Toronto neighbourhoods has shown considerable heterogeneity. The purpose of this study was to investigate the spatial variation of sporadic SARS-CoV-2 cases in Toronto neighbourhoods by detecting clusters of increased risk and investigating effects of neighbourhood-level risk factors on rates. METHODS: Data on sporadic SARS-CoV-2 cases, at the neighbourhood level, for Jan. 25 to Nov. 26, 2020, were obtained from the City of Toronto COVID-19 dashboard. We used a flexibly shaped spatial scan to detect clusters of increased risk of sporadic COVID-19. We then used a generalized linear geostatistical model to investigate whether average household size, population density, dependency ratio and prevalence of low-income households were associated with sporadic SARS-CoV-2 rates. RESULTS: We identified 3 clusters of elevated risk of SARS-CoV-2 infection, with standardized morbidity ratios ranging from 1.59 to 2.43. The generalized linear geostatistical model found that average household size (relative risk [RR] 2.17, 95% confidence interval [CI] 1.80-2.61) and percentage of low-income households (RR 1.03, 95% CI 1.02-1.04) were significant predictors of sporadic SARS-CoV-2 cases at the neighbourhood level. INTERPRETATION: During the study period, 3 clusters of increased risk of sporadic SARS-CoV-2 infection were identified, and average household size and percentage of low-income households were found to be associated with sporadic SARS-CoV-2 rates at the neighbourhood level. The findings of this study can be used to target resources and create policy to address inequities that are shown through heterogeneity of SARS-CoV-2 cases at the neighbourhood level in Toronto, Ontario.

Age-Specific Changes in Virulence Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern.

BACKGROUND: Novel variants of concern (VOCs) have been associated with both increased infectivity and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virulence of SARS-CoV-2 is closely linked to age. Whether relative increases in virulence of novel VOCs are similar across the age spectrum or are limited to some age groups is unknown. METHODS: We created a retrospective cohort of people in Ontario, Canada, who tested positive for SARS-CoV-2 and were screened for VOCs (n = 259 984) between 7 February 2021 and 31 October 2021. Cases were classified as N501Y-positive VOC, probable Delta VOC, or VOC undetected. We constructed age-specific logistic regression models to evaluate associations between N501Y-postive or Delta VOC infections and infection severity using hospitalization, intensive care unit (ICU) admission, and death as outcome variables. Models were adjusted for sex, comorbidity, vaccination status, and temporal trends. RESULTS: Infection with either N501Y-positive or Delta VOCs was associated with significant elevations in risk of hospitalization, ICU admission, and death across age groups compared with infections where a VOC was not detected. The Delta VOC increased hospitalization risk in children aged <10 years by a factor of 2.5 (adjusted odds ratio; 95% confidence interval, 1.3 to 5.0) compared with non-VOCs. There was a significant inverse relationship between age and relative increase in risk of death with the Delta VOC, with younger age groups showing a greater relative increase in risk of death than older individuals. CONCLUSIONS: SARS-CoV-2 VOCs appear to be associated with increased relative virulence of infection in all age groups, though low absolute numbers of outcomes in younger individuals make estimates in these groups imprecise.

Estimating SARS-CoV-2 Seroprevalence in Canadian Blood Donors, April 2020 to March 2021: Improving Accuracy with Multiple Assays.

We have previously used composite reference standards and latent class analysis (LCA) to evaluate the performance of laboratory assays in the presence of tarnished gold standards. Here, we apply these techniques to repeated, cross-sectional study of Canadian blood donors, whose sera underwent parallel testing with four separate SARS-CoV-2 antibody assays. We designed a repeated cross-sectional design with random cross-sectional sampling of all available retention samples (n = 1500/month) for a 12 -month period from April 2020 until March 2021. Each sample was evaluated for SARS-CoV-2 IgG antibodies using four assays an Abbott Architect assay targeting the nucleocapsid antigen (Abbott-NP, Abbott, Chicago IL) and three in-house IgG ELISAs recognizing distinct recombinant viral antigens: full-length spike glycoprotein (Spike), spike glycoprotein receptor binding domain (RBD) and nucleocapsid (NP). We used two analytic approaches to estimate SAR-CoV-2 seroprevalence: a composite reference standard and LCA. Using LCA to estimate true seropositivity status based on the results of the four antibody tests, we estimated that seroprevalence increased from 0.8% (95% CI: 0.5-1.4%) in April 2020 to 6.3% (95% CI: 5.1-7.6%) in March 2021. Our study provides further support for the use of LCA in upcoming public health crises, epidemics, and pandemics when a gold standard assay may not be available or identifiable. IMPORTANCE Here, we describe an approach to estimating seroprevalence in a low prevalence setting when multiple assays are available and yet no known gold standard exists. Because serological studies identify cases through both diagnostic testing and surveillance, and otherwise silent, unrecognized infections, serological data can be used to estimate the true infection fatality ratio of a disease. However, seroprevalence studies rely on assays with imperfect sensitivity and specificity. Seroreversion (loss of antibody response) also occurs over time, and with the advent of vaccination, distinction of antibody response resulting from vaccination as opposed to antibody response due to infection has posed an additional challenge. Our approach indicates that seroprevalence on Canadian blood donors by the end of March 2021was less than 10%. Our study supports the use of latent class analysis in upcoming public health crises, epidemics, and pandemics when a gold standard assay may not be available or identifiable.

Comparison of longitudinal trends in self-reported symptoms and COVID-19 case activity in Ontario, Canada.

BACKGROUND: Limitations in laboratory diagnostic capacity impact population surveillance of COVID-19. It is currently unknown whether participatory surveillance tools for COVID-19 correspond to government-reported case trends longitudinally and if it can be used as an adjunct to laboratory testing. The primary objective of this study was to determine whether self-reported COVID-19-like illness reflected laboratory-confirmed COVID-19 case trends in Ontario Canada. METHODS: We retrospectively analyzed longitudinal self-reported symptoms data collected using an online tool-Outbreaks Near Me (ONM)-from April 20th, 2020, to March 7th, 2021 in Ontario, Canada. We measured the correlation between COVID-like illness among respondents and the weekly number of PCR-confirmed COVID-19 cases and provincial test positivity. We explored contemporaneous changes in other respiratory viruses, as well as the demographic characteristics of respondents to provide context for our findings. RESULTS: Between 3,849-11,185 individuals responded to the symptom survey each week. No correlations were seen been self-reported CLI and either cases or test positivity. Strong positive correlations were seen between CLI and both cases and test positivity before a previously documented rise in rhinovirus/enterovirus in fall 2020. Compared to participatory surveillance respondents, a higher proportion of COVID-19 cases in Ontario consistently came from low-income, racialized and immigrant areas of the province- these groups were less well represented among survey respondents. INTERPRETATION: Although digital surveillance systems are low-cost tools that have been useful to signal the onset of viral outbreaks, in this longitudinal comparison of self-reported COVID-like illness to Ontario COVID-19 case data we did not find this to be the case. Seasonal respiratory virus transmission and population coverage may explain this discrepancy.

Estimated costs and quality-adjusted life-years lost due to N. gonorrhoeae infections acquired in 2015 in the United States: A modelling study of overall burden and disparities by age, race/ethnicity, and other factors.

Background: Disparities in the health and economic burden of gonorrhoea have not been systematically quantified. We estimated population-level health losses and costs associated with gonococcal infection and sequelae in the United States. Methods: We used probability-tree models to capture gonorrhoea sequelae and to estimate attributable disease burden in terms of the discounted lifetime costs and quality-adjusted life-years (QALYs) lost due to incident infections acquired during 2015 from the healthcare system perspective. Numbers of infections in 2015 were obtained from a published gonorrhoea transmission model. We evaluated population-level disease burden, disaggregated by sex, age, race/ethnicity, and for men who have sex with men (MSM). We conducted a multivariate sensitivity analysis for key parameters. Findings: Discounted lifetime QALYs lost per incident gonococcal infection were estimated as 0.093 (95% uncertainty interval [UI] 0.022-0.22) for women, 0.0020 (0.0015-0.0024) for heterosexual men, and 0.0015 (0.00070-0.0021) for MSM. Discounted lifetime costs per incident infection were USD 261 (109-480), 169 (88-263), and 133 (50-239), respectively. At the population level, total discounted lifetime QALYs lost due to infections acquired during 2015 were 53,293 (12,326-125,366) for women, 621 (430-872) for heterosexual men, and 1,078 (427-1,870) for MSM. Total discounted lifetime costs were USD 150 million (64-277 million), 54 million (25-92 million), and 97 million (34-197 million), respectively. The highest total burden of both QALYs and costs at the population-level was observed in Non-Hispanic Black women, and highest burden per 1,000 person-years was identified in MSM among men and American Indian/Alaska Native among women. Interpretation: Gonorrhoea causes substantial health losses and costs in the United States. These results can inform planning and prioritization of prevention services. Funding: Centers for Disease Control and Prevention, Charles A. King Trust.

Quantifying contact patterns in response to COVID-19 public health measures in Canada.

BACKGROUND: A variety of public health measures have been implemented during the COVID-19 pandemic in Canada to reduce contact between individuals. The objective of this study was to provide empirical contact pattern data to evaluate the impact of public health measures, the degree to which social contacts rebounded to normal levels, as well as direct public health efforts toward age- and location-specific settings. METHODS: Four population-based cross-sectional surveys were administered to members of a paid panel representative of Canadian adults by age, gender, official language, and region of residence during May (Survey 1), July (Survey 2), September (Survey 3), and December (Survey 4) 2020. A total of 4981 (Survey 1), 2493 (Survey 2), 2495 (Survey 3), and 2491 (Survey 4) respondents provided information about the age and setting for each direct contact made in a 24-h period. Contact matrices were constructed and contacts for those under the age of 18 years imputed. The next generation matrix approach was used to estimate the reproduction number (Rt) for each survey. Respondents with children under 18 years estimated the number of contacts their children made in school and extracurricular settings. RESULTS: Estimated Rt values were 0.49 (95% CI: 0.29-0.69) for May, 0.48 (95% CI: 0.29-0.68) for July, 1.06 (95% CI: 0.63-1.52) for September, and 0.81 (0.47-1.17) for December. The highest proportion of reported contacts occurred within the home (51.3% in May), in 'other' locations (49.2% in July) and at work (66.3 and 65.4% in September and December). Respondents with children reported an average of 22.7 (95% CI: 21.1-24.3) (September) and 19.0 (95% CI 17.7-20.4) (December) contacts at school per day per child in attendance. CONCLUSION: The skewed distribution of reported contacts toward workplace settings in September and December combined with the number of reported school-related contacts suggest that these settings represent important opportunities for transmission emphasizing the need to support and ensure infection control procedures in both workplaces and schools.

Evaluation of the relative virulence of novel SARS-CoV-2 variants: a retrospective cohort study in Ontario, Canada.

BACKGROUND: Between February and June 2021, the initial wild-type strains of SARS-CoV-2 were supplanted in Ontario, Canada, by new variants of concern (VOCs), first those with the N501Y mutation (i.e., Alpha/B1.1.17, Beta/B.1.351 and Gamma/P.1 variants) and then the Delta/B.1.617 variant. The increased transmissibility of these VOCs has been documented, but knowledge about their virulence is limited. We used Ontario's COVID-19 case data to evaluate the virulence of these VOCs compared with non-VOC SARS-CoV-2 strains, as measured by risk of hospitalization, intensive care unit (ICU) admission and death. METHODS: We created a retrospective cohort of people in Ontario who tested positive for SARS-CoV-2 and were screened for VOCs, with dates of test report between Feb. 7 and June 27, 2021. We constructed mixed-effect logistic regression models with hospitalization, ICU admission and death as outcome variables. We adjusted models for age, sex, time, vaccination status, comorbidities and pregnancy status. We included health units as random intercepts. RESULTS: Our cohort included 212 326 people. Compared with non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 52% (95% confidence interval [CI] 42%-63%) for hospitalization, 89% (95% CI 67%-117%) for ICU admission and 51% (95% CI 30%-78%) for death. Increased risk with the Delta variant was more pronounced at 108% (95% CI 78%-140%) for hospitalization, 235% (95% CI 160%-331%) for ICU admission and 133% (95% CI 54%-231%) for death. INTERPRETATION: The increasing virulence of SARS-CoV-2 VOCs will lead to a considerably larger, and more deadly, pandemic than would have occurred in the absence of the emergence of VOCs.

COVID-19 Case Age Distribution: Correction for Differential Testing by Age.

BACKGROUND: Despite expected initial universal susceptibility to a novel pandemic pathogen like SARS-CoV-2, the pandemic has been characterized by higher observed incidence in older persons and lower incidence in children and adolescents. OBJECTIVE: To determine whether differential testing by age group explains observed variation in incidence. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Persons diagnosed with SARS-CoV-2 and those tested for SARS-CoV-2. MEASUREMENTS: Test volumes from the Ontario Laboratories Information System, number of laboratory-confirmed SARS-CoV-2 cases from the Integrated Public Health Information System, and population figures from Statistics Canada. Demographic and temporal patterns in incidence, testing rates, and test positivity were explored using negative binomial regression models and standardization. Sources of variation in standardized ratios were identified and test-adjusted standardized infection ratios (SIRs) were estimated by metaregression. RESULTS: Observed disease incidence and testing rates were highest in the oldest age group and markedly lower in those younger than 20 years; no differences in incidence were seen by sex. After adjustment for testing frequency, SIRs were lowest in children and in adults aged 70 years or older and markedly higher in adolescents and in males aged 20 to 49 years compared with the overall population. Test-adjusted SIRs were highly correlated with standardized positivity ratios (Pearson correlation coefficient, 0.87 [95% CI, 0.68 to 0.95]; P < 0.001) and provided a case identification fraction similar to that estimated with serologic testing (26.7% vs. 17.2%). LIMITATIONS: The novel methodology requires external validation. Case and testing data were not linkable at the individual level. CONCLUSION: Adjustment for testing frequency provides a different picture of SARS-CoV-2 infection risk by age, suggesting that younger males are an underrecognized group at high risk for SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

A sub-national real-time epidemiological and vaccination database for the COVID-19 pandemic in Canada.

The COVID-19 pandemic has demonstrated the need for real-time, open-access epidemiological information to inform public health decision-making and outbreak control efforts. In Canada, authority for healthcare delivery primarily lies at the provincial and territorial level; however, at the outset of the pandemic no definitive pan-Canadian COVID-19 datasets were available. The COVID-19 Canada Open Data Working Group was created to fill this crucial data gap. As a team of volunteer contributors, we collect daily COVID-19 data from a variety of governmental and non-governmental sources and curate a line-list of cases and mortality for all provinces and territories of Canada, including information on location, age, sex, travel history, and exposure, where available. We also curate time series of COVID-19 recoveries, testing, and vaccine doses administered and distributed. Data are recorded systematically at a fine sub-national scale, which can be used to support robust understanding of COVID-19 hotspots. We continue to maintain this dataset, and an accompanying online dashboard, to provide a reliable pan-Canadian COVID-19 resource to researchers, journalists, and the general public.