A Population-Based Study of SARS-CoV-2 IgG Antibody Responses to Vaccination in Manitoba.

Understanding variables that influence antibody responses to COVID-19 vaccination within a population can provide valuable information on future vaccination strategies. In this population-based study, we examined the antibody responses to COVID-19 vaccination in Manitoba using residual serum specimens collected between January 2021 and March 2022 (n = 20,365). Samples were tested for spike and nucleocapsid IgG against SARS-CoV-2 using clinically validated assays. We assessed the impacts of multiple factors on post-vaccination antibody titres including type of vaccine, age, sex, geographic location, number of doses received, and timing of vaccination. Our investigation demonstrated that vaccination with one dose of Moderna mRNA-1273 elicited higher anti-spike IgG titres overall compared to Pfizer BNT162b2 vaccination, while one dose of Pfizer BNT162b2 followed by a second dose of Moderna mRNA-1273 exhibited higher titres than two doses of Pfizer BNT162b2 or Moderna mRNA-1273, irrespective of age. Age and time post-vaccination had considerable effects on antibody responses, with older age groups exhibiting lower anti-spike IgG titres than younger ages, and titres of those vaccinated with Pfizer BNT162b2 waning faster than those vaccinated with Moderna mRNA-1273 or a combination of Pfizer BNT162b2 and Moderna mRNA-1273. Antibody titres did not appear to be affected by sex or geographic location. Our results identify how factors such as age and type of vaccine can influence antibody responses to vaccination, and how antibody titres wane over time. This information highlights the importance of tailoring vaccine regimens to specific populations, especially those at increased risk of severe COVID-19 and can be used to inform future vaccination strategies, scheduling of booster doses, and public health measures.

Riding high: seroprevalence of SARS-CoV-2 after 4 pandemic waves in Manitoba, Canada, April 2020-February 2022.

BACKGROUND: Canada is emerging from the largest SARS-CoV-2 Omicron wave to date, with over 3.3 million confirmed cases. Unfortunately, PCR confirmed cases illuminate only a small portion of infections in the community and underestimate true disease burden. Population based seroprevalence studies, which measure antibody levels against a virus can more accurately estimate infection rates in the community and identify geographical and epidemiological trends to inform public health responses. METHODS: The Manitoba COVID-19 Seroprevalence (MCS) study is a population-based cross-sectional study to assess the prevalence of SARS-CoV-2 antibodies across the province. Residual convenience specimens (n = 14,901) were tested for anti-SARS-CoV-2 nucleocapsid and spike IgG antibodies from April 1, 2020 to February 31, 2022. We estimated the monthly and cumulative prevalence using an exponential decay model, accounting for population demographics, sensitivity/specificity, and antibody waning. This approach generated estimates of natural infection as well as total antibody including vaccine-induced immunity within the community. FINDINGS: After four waves of the pandemic, 60.1% (95%CI-56.6-63.7) of Manitobans have generated SARS-CoV-2 antibodies due to natural exposure independent of vaccination. Geographical analysis indicates a large portion of provincial prevalence stems from increased transmission in the Northern (92.3%) and Southern (71.8%) regional health authorities. Despite the high mortality rates reported by Manitoba, infection fatality ratios (IFR) peaked at 0.67% and declined to 0.20% following the Omicron wave, indicating parity with other national and international jurisdictions. Manitoba has achieved 93.4% (95%CI- 91.5-95.1) total antibody when including vaccination. INTERPRETATION: Our data shows that more than 3 in 5 Manitobans have been infected by SARS-CoV-2 after four waves of the pandemic. This study also identifies key geographical and age specific prevalence rates that have contributed greatly to the overall severity of the pandemic in Manitoba and will inform jurisdictions considering reduction of public health measures.

The descriptive epidemiology of pre-omicron SARS-CoV-2 breakthrough infections and severe outcomes in Manitoba, Canada.

Introduction: Vaccination plays a key role in curbing severe outcomes resulting from COVID-19 disease. With the Omicron variant and the relaxing of public health protections breakthrough infections are increasingly common, and certain groups remain at higher risk for severe outcomes from breakthrough infections. We analysed population-based public health data from Manitoba, Canada to understand characteristics of those experiencing breakthrough infections and severe outcomes from breakthrough infections. Data from previous pandemic stages can provide valuable information regarding severe outcomes associated with breakthrough infection in the Omicron and future phases. Methods: Positive SARS-CoV-2 PCR tests from Cadham Provincial Laboratory were linked to case information from the population-based Public Health Information Management System. A retrospective design was used with time-to-event analyses to examine severe outcomes among those experiencing breakthrough infection. Results: Breakthrough cases were more likely to have 2 + chronic conditions, compared to age-, sex-, and time-period matched unvaccinated cases (24% vs. 17%), with hypertension (30%), diabetes (17%), and asthma (14%) being the most prevalent chronic conditions amongst breakthrough cases. Severe outcomes resulting from breakthrough infection was associated with age and chronic conditions, with those with 2 + chronic conditions at higher risk of severe outcomes (adjusted hazard ratio: 3.6, 95% confidence intervals: 2.0-6.4). Risk of severe outcomes varied by age group, with those 70 + years at over 13 times the risk of severe outcomes (95% CI: 4.5-39.8), compared to those 18-29 years of age. Discussion: Our results demonstrate the impact of chronic conditions on the likelihood of, and severity of outcomes from breakthrough infections. These findings underscore the importance of vaccination programs prioritizing vulnerable populations.

Healthcare utilization among persons living with HIV in Manitoba, Canada, prior to HIV diagnosis: A case-control analysis.

BACKGROUND: Understanding care patterns of persons living with HIV prior to diagnosis can inform prevention opportunities, earlier diagnosis, and engagement strategies. We examined healthcare utilization among HIV-positive individuals and compared them to HIV-negative controls. METHODS: Data were from a retrospective cohort from Manitoba, Canada. Participants included individuals living with HIV presenting to care between 2007 and 2011, and HIV-negative controls, matched (1:5) by age, sex, and region. Data from population-based administrative databases included physician visits, hospitalizations, drug dispensation, and chlamydia and gonorrhea testing. Diagnoses associated with physician visits were classified according to International Classification of Diseases chapters. Conditional logistic regression models were used to compare cases/controls, with adjusted odds ratios (AORs) and their 95% confidence intervals (95% CI) reported. RESULTS: A total of 193 cases and 965 controls were included. Physician visits and hospitalizations were higher for cases, compared to controls. In the 2 years prior to case date, cases were more likely to be diagnosed with "blood disorders" (AOR: 4.2, 95% CI: 2.0-9.0), be treated for mood disorders (AOR: 2.4, 95% CI: 1.6-3.4), and to have 1+ visits to a hospital (AOR: 2.2, 95% CI: 1.4-3.6). CONCLUSION: Opportunities exist for prevention, screening, and earlier diagnosis. There is a need for better integration of healthcare services with public health.

Comparaison de l'infectivité du coronavirus du syndrome respiratoire aigu sévère 2 chez les enfants et les adultes.

CONTEXTE: Le rôle des enfants dans la propagation et la transmission communautaire du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) est encore mal compris. Nous visons à quantifier l'infectivité du SRAS-CoV-2 d'échantillons nasopharyngés provenant d'enfants comparativement à ceux provenant d'adultes. MÉTHODES: Nous avons obtenu des écouvillons nasopharyngés de cas adultes et pédiatriques de la maladie à coronavirus 2019 (COVID-19) ainsi que de leurs contacts qui ont obtenu un résultat positif à la présence du SRAS-CoV-2 lors d'un test de dépistage au Manitoba entre les mois de mars et décembre 2020. Nous avons comparé la croissance virale en culture cellulaire, les valeurs de cycle seuil de test d'amplification en chaîne par polymérase couplé à une transcription inverse (RT-PCR) de l'enveloppe (E) du gène du SRAS-CoV-2 et de la dose infectieuse pour 50 % de la culture tissulaire (DICT50/mL) entre les adultes et les enfants. RÉSULTATS: Parmi les 305 échantillons positifs à la présence du SRAS-CoV-2 validés par RT-PCR, 97 échantillons provenaient d'enfants de 10 ans et moins, 78 échantillons d'enfants de 11­17 ans et 130 échantillons d'adultes (≥ 18 ans). On a observé une croissance virale en culture dans 31 % des échantillons, dont 18 (19 %) échantillons d'enfants de 10 ans et moins, 18 (23 %) d'enfants de 11­17 ans et 57 (44 %) d'adultes (enfants c. adultes, rapport de cotes 0,45; intervalle de confiance [IC] à 95 % 0,28­0,72). Le cycle seuil était de 25,1 (IC à 95 % 17,7­31,3) chez les enfants de 10 ans et moins, 22,2 (IC à 95 % 18,3­29,0) chez les enfants de 11­17 ans et 18,7 (IC à 95 % 17,9­30,4) chez les adultes (p < 0,001). La DICT50/mL médiane était considérablement plus faible chez les enfants de 11­17 ans (316, écart interquartile [EI] 178­2125) que chez les adultes (5620, EI 1171­17 800, p < 0,001). Le cycle seuil était un indicateur exact d'une culture positive chez les enfants et les adultes (aire sous la courbe de la fonction d'efficacité du récepteur, 0,87, IC à 95 % 0,81­0,93 c. 0,89, IC à 95 % 0,83­0,96, p = 0,6). INTERPRÉTATION: Comparés aux adultes, les enfants qui ont obtenu un résultat positif à un test de dépistage du SRAS-CoV-2 à l'aide d'un écouvillon nasopharyngé étaient moins susceptibles de présenter une croissance du virus en culture et obtenaient un cycle seuil plus élevé et une concentration virale moins élevée, indiquant que les enfants ne sont pas les principaux vecteurs de la transmission du SRAS-CoV-2.

Infectivity of severe acute respiratory syndrome coronavirus 2 in children compared with adults.

BACKGROUND: The role of children in the transmission and community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. We aimed to quantify the infectivity of SARS-CoV-2 in nasopharyngeal samples from children compared with adults. METHODS: We obtained nasopharyngeal swabs from adult and pediatric cases of coronavirus disease 2019 (COVID-19) and from their contacts who tested positive for SARS-CoV-2 in Manitoba between March and December 2020. We compared viral growth in cell culture, cycle threshold values from the reverse transcription polymerase chain reaction (RT-PCR) of the SARS-CoV-2 envelope (E) gene and the 50% tissue culture infective dose (TCID50/mL) between adults and children. RESULTS: Among 305 samples positive for SARS-CoV-2 by RT-PCR, 97 samples were from children aged 10 years or younger, 78 were from children aged 11-17 years and 130 were from adults (≥ 18 yr). Viral growth in culture was present in 31% of samples, including 18 (19%) samples from children 10 years or younger, 18 (23%) from children aged 11-17 years and 57 (44%) from adults (children v. adults, odds ratio 0.45, 95% confidence interval [CI] 0.28-0.72). The cycle threshold was 25.1 (95% CI 17.7-31.3) in children 10 years or younger, 22.2 (95% CI 18.3-29.0) in children aged 11-17 years and 18.7 (95% CI 17.9-30.4) in adults (p < 0.001). The median TCID50/mL was significantly lower in children aged 11-17 years (316, interquartile range [IQR] 178-2125) than adults (5620, IQR 1171 to 17 800, p < 0.001). Cycle threshold was an accurate predictor of positive culture in both children and adults (area under the receiver-operator curve, 0.87, 95% CI 0.81-0.93 v. 0.89, 95% CI 0.83-0.96, p = 0.6). INTERPRETATION: Compared with adults, children with nasopharyngeal swabs that tested positive for SARS-CoV-2 were less likely to grow virus in culture, and had higher cycle thresholds and lower viral concentrations, suggesting that children are not the main drivers of SARS-CoV-2 transmission.

The HIV care cascade in Manitoba, Canada: Methods, measures, and estimates to meet local needs.

BACKGROUND AND OBJECTIVE: We describe the development of the first HIV care cascade for Manitoba, Canada, detailing steps taken to establish indicator definitions for each cascade step, and derive a full complement of local estimates. METHODS: Manitoba is a Canadian Prairie Province with disproportionately high annual HIV incidence. In 2013, a clinical cohort of people living with HIV was established within the primary HIV care program in Manitoba. Using cohort data from 2017, we describe the creation of a set of indicator definitions and calculate estimates for each cascade step to create the first Manitoban cascade model. RESULTS: Of the 703 cohort participants categorized as alive and diagnosed, 638 (90.8%) were in care, 606 (86.2%) retained in care, 573 (81.5%) on treatment, and 523 (74.4%) virologically suppressed. The greatest point of leakage occurred between the first and second steps; 9.3% of those alive and diagnosed in 2017 were not in care in the same calendar year. CONCLUSION: This is the first comprehensive examination of HIV clinical epidemiology in Manitoba using a cascade framework, with the potential inform programming to improve service coverage within Manitoba and significantly contribute to evidence informing provincial policies to support these efforts.

Cohort profile: the LHIV-Manitoba clinical cohort of people living with HIV in Manitoba, Canada.

PURPOSE: The LHIV-Manitoba cohort was developed as a way to provide a comprehensive source of HIV-related health information in the central Canadian Prairie province of Manitoba. The cohort will provide important information as we aim to better understand local HIV epidemiology and address key knowledge and practice gaps in HIV prevention, treatment and care programming in the province. PARTICIPANTS: In total, 890 individuals, aged 18 or older and living or receiving HIV care in Manitoba are enrolled in the cohort. A complete clinical dataset exists for 725 participants, which includes variables on sociodemographic characteristics, comorbidities and co-infections, self-reported HIV exposure categories and HIV clinical indicators. A limited clinical dataset exists for an additional 165 individuals who were enrolled posthumously. 97.5% of cohort participants' clinical records are linked to provincial administrative health datasets. FINDINGS TO DATE: The average age of cohort participants is 49.7 years. Approximately three-quarters of participants are male, 42% self-identified as white and 42% as Indigenous. The majority of participants (64%) reported condomless vaginal sex as a risk exposure for HIV. Nearly one-fifth (18%) of participants have an active hepatitis C virus infection and the cohort's median CD4 count increased from 316 cells/mm3 to 518 cells/mm3 between time of entry into care and end of the first quarter in 2019. FUTURE PLANS: The LHIV-Manitoba cohort is an open cohort, and as such, participant enrolment, data collection and analyses will be continually ongoing. Future analyses will focus on the impact of provincial drug plans on clinical outcomes, determinants of mortality among cohort participants and deriving estimates for a local HIV care cascade.

Large community mumps outbreak in Manitoba, Canada, September 2016-December 2018.

BACKGROUND: After routine mumps immunization programs were implemented in Manitoba in the 1980s, incidence was low, with 0-9 cases of disease annually. In September 2016, a mumps outbreak began in fully vaccinated university students in Winnipeg, Manitoba. OBJECTIVE: We describe the investigation of this province-wide mumps outbreak, which lasted between September 2016 and December 2018. We present the details of public health measures implemented and challenges encountered. Possible contributing factors to the sustained transmission are also provided. METHODS: Probable and confirmed cases of mumps were investigated by public health departments using the investigation form developed for this outbreak. Confirmed mumps cases were linked to the provincial immunization registry. An outbreak response team planned and implemented control measures across the province. RESULTS: The outbreak began in vaccinated university students in September 2016 and spread across the province. Activity was high and prolonged in the northern remote areas. By the end of 2018, 2,223 cases had been confirmed. All age groups were affected, and incidence was highest among people aged 18-29 years. Two-dose coverage of mumps-containing vaccine in confirmed cases was close to 70%. CONCLUSION: This prolonged outbreak revealed a large vulnerable population likely resulting from under-vaccination and waning vaccine-induced immunity in the absence of natural boosting from exposure to mumps virus. It is important to maintain high two-dose coverage with mumps-containing vaccines. A third dose of mumps-containing vaccine in future outbreaks may be considered.

Creating Clinical Cohorts: Challenges Encountered in Two Canadian Provinces.

In 2013, the Living with HIV (LHIV) Innovation team established clinical cohorts of people living with HIV in Manitoba and Newfoundland and Labrador, and they linked the data to provincial health administrative databases. Access to these data enabled researchers to conduct studies across provincial borders; contribute to a national dialogue on HIV health system performance; and give recommendations for evidence-based healthcare, health policy and public health. However, research funding is episodic; maintaining cohorts requires stable funding. We support the establishment of a cross-jurisdictional approach to facilitate streamlined data collection and linkage without interruption and to allow for meaningful analysis in order to inform national policies.

Laboratory Detection of First and Repeat Chlamydia Cases Influenced by Testing Patterns: A Population-Based Study.

OBJECTIVES: The purpose of this study was to describe and explore potential driving factors of trends in reported chlamydia infections over time in Manitoba, Canada. METHODS: Surveillance and laboratory testing data from Manitoba Health, Seniors and Active Living were analysed using SAS v9.4. Kaplan-Meier plots of time from the first to second chlamydia infection were constructed, and Cox proportional hazards regression was used to estimate the risk of second repeat chlamydia infections in males and females. RESULTS: Overall, the number of reported infections found mirrored the number of tests conducted. From 2008 to 2014, the number of first infections found among females decreased as the number of first tests conducted among females also decreased. Between 2008 and 2012, the number of repeat tests among females increased and was accompanied by an increase in the number of repeat positive results from 2009 to 2013. From 2008 to 2016, the number of repeat tests and repeat positive results increased steadily among males. CONCLUSIONS: Chlamydia infection rates consistently included a subset composed of repeat infections. The number of cases identified appears to mirror testing volumes, drawing into question incidence calculations that do not include testing volumes. SUMMARY BOX: 1) What is the current understanding of this subject? Chlamydia incidence is high in Manitoba, particularly among young women and in northern Manitoba.2) What does this report add to the literature? This report suggests that incidence calculated using case-based surveillance data alone does not provide an accurate estimate of chlamydia incidence in Manitoba and is heavily influenced by testing patterns.3) What are the implications for public health practice? In general, improving testing rates in clinical practices as well as through the provision of rapid services in non-clinical venues could result in higher screening and treatment rates. In turn, this could lead to a better understanding of true disease occurrence.

The effect of timing of oseltamivir chemoprophylaxis in controlling influenza A H3N2 outbreaks in long-term care facilities in Manitoba, Canada, 2014-2015: a retrospective cohort study.

OBJECTIVE: This study examined the effect of the timing of administration of oseltamivir chemoprophylaxis for the control of influenza A H3N2 outbreaks among residents in long-term care facilities (LTCFs) in Manitoba, Canada, during the 2014-2015 influenza season. METHODS: A retrospective cohort study was conducted of all LTCF influenza A H3N2 outbreaks (n=94) using a hierarchical logistic regression analysis. The main independent variable was how many days passed between the start of the outbreak and commencement of oseltamivir chemoprophylaxis. The dependent variable was whether each person in the institution developed influenza-like illness (yes or no). RESULTS: Delay of oseltamivir chemoprophylaxis was associated with increased odds of infection in both univariate (t=5·41; df=51; P<·0001) and multivariable analyses (t=6·04; df=49; P<·0001) with an adjusted odds ratio of 1.3 (95% confidence interval [CI], 1·2-1·5) per day for influenza A H3N2. CONCLUSIONS: The sooner chemoprophylaxis is initiated, the lower the odds of secondary infection with influenza in LTCFs during outbreaks caused by influenza A H3N2 in Manitoba. For every day that passed from the start of the outbreak to the initiation of oseltamivir, the odds of a resident at risk of infection in the facility developing symptomatic infection increased by 33%.

Prior history of testing for syphilis, hepatitis B and hepatitis C among a population-based cohort of HIV-positive individuals and their HIV-negative controls.

Understanding patterns of serological testing for hepatitis B & C, and syphilis among HIV-positive individuals, prior to HIV diagnosis, can inform HIV diagnosis, engagement and prevention strategies. This was a population-based, retrospective analysis of prior serological testing among HIV-positive individuals in Manitoba, Canada. HIV cases were age-, sex- and region-matched to HIV-negative controls at a 1:5 ratio. Conditional logistic regression was used to examine previous serological tests and HIV status. Odds ratios (ORs) and their 95% confidence intervals (95% CI) were reported. A total of 193 cases and 965 controls were included. In the 5 years prior to diagnosis, 50% of cases had at least one test, compared to 26% of controls. Compared to those who did not have serological testing in the 5 years prior to HIV infection, those who had one serological test were at twice the odds of being HIV positive (OR: 1.9, 95% CI: 1.2-2.9), while those with 2 or more tests were at even higher odds (OR: 5.5, 95%CI: 3.7-8.4). HIV cases had higher serological testing rates. Interactions between public health and other healthcare providers should be strengthened.