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.

Causal and Associational Language in Observational Health Research: A Systematic Evaluation.

We estimated the degree to which language used in the high-profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched for and screened 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, 3 reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as none (no causal implication) in 13.8%, weak in 34.2%, moderate in 33.2%, and strong in 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers' ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.

Case-cohort design as an efficient approach to evaluating COVID-19 vaccine effectiveness, waning, heterologous immune effect and optimal dosing interval.

Though widely applied in other epidemiological fields, the case-cohort study design has seen little application in the field of vaccinology. Case-cohort studies use probabilistic sampling and reweighting to draw inferences about effects (in this case vaccine efficacy) at the population level in an efficient manner. The SARS-CoV-2 pandemic was met with high vaccine uptake, and high rates of population testing prior to the emergence of Omicron variants of concern, in Ontario, Canada, providing an ideal environment for application of case-cohort methodology. We combined a population-based case line list and vaccination database for the province of Ontario between December 2020 and October 2021. Risk of infection after vaccination was evaluated in all laboratory-confirmed vaccinated SARS-CoV-2 cases, and a 2 % sample of vaccinated controls, evaluated using survival analytic methods, including construction of Cox proportional hazards models. Vaccination status was treated as a time-varying covariate. First and second doses of SARS-CoV-2 vaccine markedly reduced risk of infection (first dose efficacy 68 %, 95 % CI 67 %-69 %; second dose efficacy 88 %, 95 % CI 87-88 %). In multivariable models, extended dosing intervals were associated with lowest risk of breakthrough infection (HR for redosing 0.64 (95 % CI 0.61-0.67) at 6-8 weeks). Heterologous vaccine schedules that mixed viral vector vaccine first doses with mRNA second doses were significantly more effective than mRNA only vaccines. Risk of infection largely vanished during the time period 4-6 months after the second vaccine dose, but rose markedly thereafter. We conclude that a case-cohort design provided an efficient means to identify strong protective effects associated with SARS-CoV-2 vaccination in real time, and also served to quantify the timing and magnitude of infection breakthrough risk in the same cohort. Heterologous vaccination and extended dosing intervals improved the durability of immune response.

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.

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.

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.

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.

Lyme Disease Risk of Exposure to Blacklegged Ticks (Acari: Ixodidae) Infected with Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in Pittsburgh Regional Parks.

Lyme disease is the most commonly reported vector-borne illness and sixth most commonly reported notifiable infectious disease in the United States. The majority of cases occur in the Northeast and upper-Midwest, and the number and geographic distribution of cases is steadily increasing. The blacklegged tick (Ixodes scapularis Say) is the principal vector of the Lyme disease spirochete (Borrelia burgdorferi sensu stricto) in eastern North America. Although Lyme disease risk has been studied in residential and recreational settings across rural to urban landscapes including metropolitan areas, risk within U.S. cities has not been adequately evaluated despite the presence of natural and undeveloped public parkland where visitors could be exposed to B. burgdorferi-infected I. scapularis. We studied the occurrence of I. scapularis and infection prevalence of B. burgdorferi in four insular regional parks within the city of Pittsburgh to assess Lyme disease risk of exposure to infected adults and nymphs. We found that the density of I. scapularis adults (1.16 ± 0.21 ticks/100 m2) and nymphs (3.42 ± 0.45 ticks/100 m2), infection prevalence of B. burgdorferi in adults (51.9%) and nymphs (19.3%), and density of infected adults (0.60 ticks/100 m2) and nymphs (0.66 ticks/100 m2) are as high in these city parks as nonurban residential and recreational areas in the highly endemic coastal Northeast. These findings emphasize the need to reconsider, assess, and manage Lyme disease risk in greenspaces within cities, especially in high Lyme disease incidence states.

Zebrafish as a Model to Assess the Teratogenic Potential of Nitrite.

High nitrate levels in the environment may result in congenital defects or miscarriages in humans. Presumably, this is due to the conversion of nitrate to nitrite by gut and salivary bacteria. However, in other mammalian studies, high nitrite levels do not cause birth defects, although they can lead to poor reproductive outcomes. Thus, the teratogenic potential of nitrite is not clear. It would be useful to have a vertebrate model system to easily assess teratogenic effects of nitrite or any other chemical of interest. Here, we demonstrate the utility of zebrafish (Danio rerio) to screen compounds for toxicity and embryonic defects. Zebrafish embryos are fertilized externally and have rapid development, making them a good model for teratogenic studies. We show that increasing the time of exposure to nitrite negatively affects survival. Increasing the concentration of nitrite also adversely affects survival, whereas nitrate does not. For embryos that survive nitrite exposure, various defects can occur, including pericardial and yolk sac edema, swim bladder noninflation, and craniofacial malformation. Our results indicate that the zebrafish is a convenient system for studying the teratogenic potential of nitrite. This approach can easily be adapted to test other chemicals for their effects on early vertebrate development.

Effects of nitrite on development of embryos and early larval stages of the zebrafish (Danio rerio).

Epidemiological studies suggest that high nitrate levels in food and water may cause birth defects or spontaneous abortions in humans. Experimental mammalian studies show that high nitrite levels adversely affect reproductive outcomes, but have not shown congenital malformations. Consequently, the teratogenic potential of nitrite is unclear. In this study, the effects of nitrite on development of zebrafish embryos and early larval stages were investigated. Eggs were exposed to ethanol (a known teratogen), nitrite, or nitrate for 24 or 96 hours, and larvae examined at 120 hours. Sublethal exposure to 300 mM ethanol for 24 hours caused severe pericardial and yolk sac edema, craniofacial and axial malformations, and swim bladder noninflation. The 96 hour LC(50) for nitrite was 411 mg/L. Less severe edema, craniofacial (but not axial) malformations, swim bladder noninflation, and immobility were observed after sublethal exposure to nitrite between 10 and 300 mg/L for 96 hours. Exposure to nitrite for 24 hours at concentrations as high as 2000 mg/L was not lethal. Only axial malformations and swim bladder noninflation were observed at 1500 mg/L. The results demonstrate that sublethal nitrite concentrations cause developmental defects. The type and magnitude of these defects differed after 24 and 96 hours of exposure.