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.

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 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.

Evaluation of an automated feedback intervention to improve antibiotic prescribing among primary care physicians (OPEN Stewardship): a multinational controlled interrupted time-series study.

Tools to advance antimicrobial stewardship in the primary health care setting, where most antimicrobials are prescribed, are urgently needed. The aim of this study was to evaluate OPEN Stewarship (Online Platform for Expanding aNtibiotic Stewardship), an automated feedback intervention, among a cohort of primary care physicians. We performed a controlled, interrupted time-series study of 32 intervention and 725 control participants, consisting of primary care physicians from Ontario, Canada and Southern Israel, from October 2020 to December 2021. Intervention participants received three personalized feedback reports targeting several aspects of antibiotic prescribing. Study outcomes (overall prescribing rate, prescribing rate for viral respiratory conditions, prescribing rate for acute sinusitis, and mean duration of therapy) were evaluated using multilevel regression models. We observed a decrease in the mean duration of antibiotic therapy (IRR = 0.94; 95% CI: 0.90, 0.99) in intervention participants during the intervention period. We did not observe a significant decline in overall antibiotic prescribing (OR = 1.01; 95% CI: 0.94, 1.07), prescribing for viral respiratory conditions (OR = 0.87; 95% CI: 0.73, 1.03), or prescribing for acute sinusitis (OR = 0.85; 95% CI: 0.67, 1.07). In this antimicrobial stewardship intervention among primary care physicians, we observed shorter durations of therapy per antibiotic prescription during the intervention period. The COVID-19 pandemic may have hampered recruitment; a dramatic reduction in antibiotic prescribing rates in the months before our intervention may have made physicians less amenable to further reductions in prescribing, limiting the generalizability of the estimates obtained.IMPORTANCEAntibiotic overprescribing contributes to antibiotic resistance, a major threat to our ability to treat infections. We developed the OPEN Stewardship (Online Platform for Expanding aNtibiotic Stewardship) platform to provide automated feedback on antibiotic prescribing in primary care, where most antibiotics for human use are prescribed but where the resources to improve antibiotic prescribing are limited. We evaluated the platform among a cohort of primary care physicians from Ontario, Canada and Southern Israel from October 2020 to December 2021. The results showed that physicians who received personalized feedback reports prescribed shorter courses of antibiotics compared to controls, although they did not write fewer antibiotic prescriptions. While the COVID-19 pandemic presented logistical and analytical challenges, our study suggests that our intervention meaningfully improved an important aspect of antibiotic prescribing. The OPEN Stewardship platform stands as an automated, scalable intervention for improving antibiotic prescribing in primary care, where needs are diverse and technical capacity is limited.

An Evaluation of the Impact of an OPEN Stewardship Generated Feedback Intervention on Antibiotic Prescribing among Primary Care Veterinarians in Canada and Israel.

An interrupted time-series study design was implemented to evaluate the impact of antibiotic stewardship interventions on antibiotic prescribing among veterinarians. A total of 41 veterinarians were enrolled in Canada and Israel and their prescribing data between 2019 and 2021 were obtained. As an intervention, veterinarians periodically received three feedback reports comprising feedback on the participants' antibiotic prescribing and prescribing guidelines. A change in the level and trend of antibiotic prescribing after the administration of the intervention was compared using a multi-level generalized linear mixed-effect negative-binomial model. After the receipt of the first (incidence rate ratios [IRR] = 0.88; 95% confidence interval (CI): 0.79, 0.98), and second (IRR = 0.85; 95% CI: 0.75, 0.97) feedback reports, there was a reduced prescribing rate of total antibiotic when other parameters were held constant. This decline was more pronounced among Israeli veterinarians compared to Canadian veterinarians. When other parameters were held constant, the prescribing of critical antibiotics by Canadian veterinarians decreased by a factor of 0.39 compared to that of Israeli veterinarians. Evidently, antibiotic stewardship interventions can improve antibiotic prescribing in a veterinary setting. The strategy to sustain the effect of feedback reports and the determinants of differences between the two cohorts should be further explored.

Hepatitis B and C in individuals with a history of antipsychotic medication use: A population-based evaluation.

BACKGROUND: A better understanding of links between mental illness and risk of bloodborne infectious disease could inform preventive and therapeutic strategies in individuals with mental illness. METHODS: We performed a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) to estimate the seroprevalence of hepatitis B and C in individuals with and without a prior prescription for antipsychotic medications, and to determine whether differences in seroprevalence could be explained by differential distribution in known infection risk factors. Multivariable logistic regression models were used to examine the association between receipt of antipsychotic medication and HBV and HCV seropositivity. RESULTS: Those who had HBV core antibody had 1.64 (95% CI: 0.89, 3.02) times the odds and those with HCV antibody (anti-HCV) had 3.48 (95% CI: 1.71, 7.09) times the odds of having a prescription for at least one antipsychotic medication compared to those who did not have HBV core antibody or HCV antibody, respectively. While prior antipsychotic receipt was a potent risk marker for HCV seropositivity, risk was explained by adjusting for known bloodborne infection risk factors (adjusted ORs 1.01 [95% CI: 0.50, 2.02] and 1.38 [95% CI: 0.44, 4.36] for HBV and HCV, respectively). CONCLUSIONS: Prior receipt of antipsychotic medications is a strong predictor of HCV (and to a lesser extent HBV) seropositivity. Treatment with antipsychotic medications should be considered as additional risk markers for individuals who may benefit from targeted prevention, screening, and harm reduction interventions for HCV.

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.

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.

Seasonality of influenza and coseasonality with avian influenza in Bangladesh, 2010-19: a retrospective, time-series analysis.

BACKGROUND: Seasonal and avian influenza viruses circulate among human and poultry populations in Bangladesh. However, the epidemiology of influenza is not well defined in this setting. We aimed to characterise influenza seasonality, examine regional heterogeneity in transmission, and evaluate coseasonality between circulating influenza viruses in Bangladesh. METHODS: In this retrospective, time-series study, we used data collected between January, 2010, and December, 2019, from 32 hospital-based influenza surveillance sites across Bangladesh. We estimated influenza peak timing and intensity in ten regions using negative binomial harmonic regression models, and applied meta-analytic methods to determine whether seasonality differed across regions. Using live bird market surveillance data in Dhaka, Bangladesh, we estimated avian influenza seasonality and examined coseasonality between human and avian influenza viruses. FINDINGS: Over the 10-year study period, we included 8790 human influenza cases and identified a distinct influenza season, with an annual peak in June to July each year (peak calendar week 27·6, 95% CI 26·7-28·6). Epidemic timing varied by region (I2=93·9%; p<0·0001), with metropolitan regions peaking earlier and epidemic spread following a spatial diffusion pattern based on geographical proximity. Comparatively, avian influenza displayed weak seasonality, with moderate year-round transmission and a small peak in April (peak calendar week 14·9, 95% CI 13·2-17·0), which was out of phase with influenza peaks in humans. INTERPRETATION: In Bangladesh, influenza prevention and control activities could be timed with annual seasonality, and regional heterogeneity should be considered in health resource planning. Year-round avian influenza transmission poses a risk for viral spillover, and targeted efforts will be crucial for mitigating potential reassortment and future pandemic threats. FUNDING: Canadian Institute of Health Research Vanier Canada Graduate Scholarship.

Examining the role of person-to-person transmission during a verocytotoxigenic Escherichia coli outbreak in Ontario, Canada.

OBJECTIVE: Person-to-person transmission can occur during outbreaks of verotoxigenic Escherichia coli (VTEC), however the impact of this transmission route is not well understood. This study aimed to examine the role of person-to-person transmission during a VTEC outbreak, and how targeting this route may reduce outbreak size. A deterministic compartmental model describing a VTEC outbreak was constructed and fit to data from a 2008 outbreak in Ontario, Canada. Using the best-fit model, simulations were run to calculate the: reduction in transmission rate after implementing interventions, proportion of cases infected through both transmission routes, and number of cases prevented by interventions. Latin hypercube sensitivity analysis was conducted to examine the sensitivity of the outbreak size to the model parameters. RESULTS: Based on the best-fit model, ~ 14.25% of the cases likely arose due to person-to-person transmission. Interventions reduced this transmission rate by ~ 73%, causing a reduction in outbreak size of ~ 17% (47 cases). Sensitivity analysis showed that the model was highly sensitive to changes in all parameters of the model. The model demonstrates that person-to-person could be an important transmission route during VTEC outbreaks. Targeting this route of transmission through hand hygiene and work exclusions could reduce the final outbreak size.

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.

The Association Between Self-Reported Non-Injection Cocaine Use and Hepatitis C in the United States: An Analysis of the National Health and Nutrition Examination Survey.

OBJECTIVE: Previous studies conducted on hepatitis C virus (HCV) transmission have focused primarily on its transmission among people who inject drugs. However, there is evidence that transmission may also occur through the sharing of contaminated non-injection implements used to consume drugs nasally, orally, or by inhalation. Studies to date have not conclusively established a relationship between these routes of cocaine use and HCV. We quantified the association between cocaine use and HCV, specifically among individuals who have never injected an illicit substance. METHOD: Data from the 2011-2018 National Health and Nutrition Examination Survey were analyzed. Multivariable logistic regression was used to test for an association between cocaine use and HCV among 10,106 individuals (5,201 females). Covariates included age, race, sex, education, income, and immigrant status. RESULTS: In the unadjusted model, individuals who reported cocaine use had 4.79 (95% CI [2.70, 8.47]) times the odds of ever having HCV compared with those who did not use cocaine. In the adjusted model, individuals who reported cocaine use had 4.48 (95% CI [2.36, 8.50]) times the odds of ever having HCV compared with those who did not use cocaine. CONCLUSIONS: This study highlights that individuals who report non-injection cocaine use have an inflated risk of HCV compared with individuals who report no cocaine use. Harm reduction interventions to reduce the transmission of HCV should therefore be targeted to all people who use drugs, including those who use cocaine orally, intra-nasally, and by inhalation.

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.

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.