Cross-Canada Variability in Blood Donor SARS-CoV-2 Seroprevalence by Social Determinants of Health.

We compared the seroprevalence of SARS-CoV-2 anti-nucleocapsid antibodies in blood donors across Canadian regions in 2021. The seroprevalence was the highest in Alberta and the Prairies, and it was so low in Atlantic Canada that few correlates were observed. Being male and of young age were predictive of seropositivity. Racialization was associated with higher seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. Living in a materially deprived neighborhood predicted higher seroprevalence, but it was more linear across quintiles in Alberta and the Prairies, whereas in British Columbia and Ontario, the most affluent 60% were similarly low and the most deprived 40% similarly elevated. Living in a more socially deprived neighborhood (more single individuals and one parent families) was associated with lower seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. These data show striking variability in SARS-CoV-2 seroprevalence across regions by social determinants of health. IMPORTANCE Canadian blood donors are a healthy adult population that shows clear disparities associated with racialization and material deprivation. This underscores the pervasiveness of the socioeconomic gradient on SARS-CoV-2 infections in Canada. We identify regional differences in the relationship between SARS-CoV-2 seroprevalence and social determinants of health. Cross-Canada studies, such as ours, are rare because health information is under provincial jurisdiction and is not available in sufficient detail in national data sets, whereas other national seroprevalence studies have insufficient sample sizes for regional comparisons. Ours is the largest seroprevalence study in Canada. An important strength of our study is the interpretation input from a public health team that represented multiple Canadian provinces. Our blood donor seroprevalence study has informed Canadian public health policy at national and provincial levels since the start of the SARS-CoV-2 pandemic.

Seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies among a cohort of children and adolescents in Montreal, Canada

ImportanceRepeated serological testing for SARS-CoV-2 allows the monitoring of antibody dynamics in populations, including detecting infections that are missed by RT-PCR or antigen testing. Understanding the factors associated with seroconversion and seroreversion as well as the duration of infection-induced antibodies can also inform public health recommendations regarding disease prevention and mitigation efforts. ObjectiveTo use serological testing to assess the prevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies in children and adolescents in Montreal, Canada. DesignThis analysis reports on three rounds of data collection from a prospective cohort study (Enfants et COVID-19: Etude de seroprevalence [EnCORE]). The study rounds occurred as follows: Round 1 October 2020-March 2021, Round 2 May to July 2021, and Round 3 November 2021 to January 2022. Most Round 3 samples were collected prior to the spread of the Omicron BA.1 variant in Quebec. SettingPopulation-based sample. ParticipantsChildren and adolescents aged 2 to 17 years in Montreal, Canada. ExposurePotential exposure to SARS-CoV-2. Main Outcomes and MeasuresParticipants provided dried blood spots (DBS) for antibody detection and parents completed online questionnaires for sociodemographics and COVID-19 symptoms and testing history. The serostatus of participants was determined by enzyme-linked immunosorbent assays (ELISAs) using the receptor-binding domain (RBD) from the spike protein and the nucleocapsid protein (N) as antigens. We estimated seroprevalence for each round of data collection and by participant and household characteristics. Seroconversion rates were calculated as were the likelihoods of remaining seropositive at six months and one year. ResultsThe study included DBS samples from 1 632, 936, and 723 participants in the first, second, and third rounds of data collection, respectively. The baseline seroprevalence was 5{middle dot}8% (95% CI 4{middle dot}8-7{middle dot}1), which increased to 10{middle dot}5% and 10{middle dot}9% for the respective follow-ups (95% CI 8{middle dot}6-12{middle dot}7; 95% CI 8{middle dot}8-13{middle dot}5). The overall average crude rate of seroconversion over the study period was 12{middle dot}7 per 100 person-years (95% CI 10{middle dot}9-14{middle dot}5). Adjusted hazard rates of seroconversion by child and household characteristics showed higher rates in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes less than 100K. The likelihood of remaining seropositive at six months was 67% (95% CI 59-76) and dropped to 19% (95% CI 11%-33%) at one year. Conclusions and RelevanceThe data reported here provide estimates of pre-Omicron seroprevalence, seroconversion rates and time to seroreversion in a population-based cohort of children and adolescents. Serological studies continue to provide valuable contributions for infection prevalence estimates and help us better understand the dynamics of antibody levels following infection. Continued study of seroconversion and seroreversion can inform public health recommendations such as COVID-19 vaccination and booster schedules. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat was the rate of seroconversion and time to seroreversion for SARS-CoV-2 antibodies among children and adolescents in Montreal between October 2020 to January 2022? FindingsThe overall average crude rate of seroconversion was 12{middle dot}7 per 100 person-years (95% CI 10{middle dot}9-14{middle dot}5). We observed higher rates of seroconversion in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes less than 100K. Among all children who seroconverted, 71% had not been previously diagnosed with COVID-19. Median time to seroreversion was 7{middle dot}5 months. MeaningEven before the emergence of the Omicron variants, we observed a high rate of seroconversion for infection-induced SARS-CoV-2 antibodies along with widespread antibody waning by one year. Many children and adolescents seroconverted despite not receiving a prior COVID-19 diagnosis, indicating that RT-PCR and antigen testing continue to underestimate true disease prevalence.

Immunogenicity of Pfizer-BioNTech COVID-19 mRNA Primary Vaccination Series in Recovered Individuals Depends on Symptoms at Initial Infection.

ImportancePublic health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. We present detailed immunological evidence to clarify the requirements for one-or two-dose primary vaccination series for naturally primed individuals. ObjectiveEvaluate the immune response to COVID-19 mRNA vaccines in healthcare workers (HCWs) who recovered from a SARS-CoV-2 infection. DesignMulticentric observational prospective cohort study of HCWs with a PCR-confirmed SARS-CoV-2 infection designed to evaluate the dynamics of T and B cells immune responses to primary infection and COVID-19 mRNA vaccination over 12 months. ParticipantsUnvaccinated HCWs with PCR-confirmed SARS-CoV-2 infection were selected based on the presence or absence of symptoms at infection and serostatus at enrollment. Age- and sex-matched adults not infected with SARS-CoV-2 prior to vaccination were included as naive controls. ExposureVaccination with Pfizer BioNTech BNT162b2 mRNA vaccine. Main Outcome(s) and Measure(s)Immunity score (zero to three), before and after vaccination, based on anti-RBD IgG ratio, serum capacity to neutralize live virus and IFN-{gamma} secretion capacity in response to SARS-CoV-2 peptide pools above the positivity threshold for each of the three assays. We compared the immunity score between groups based on subjects symptoms at diagnosis and/or serostatus prior to vaccination. ResultsNone of the naive participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naive individuals, with significantly weaker responses than those who were symptomatic during infection. Conclusions and RelevanceIndividuals who did not develop symptoms during their initial SARS-CoV-2 infection and were seronegative prior to vaccination present immune responses comparable to that of naive individuals. These findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection. KEY POINTS QuestionIs a single dose of COVID-19 mRNA vaccine sufficient to induce robust immune responses in individuals with prior SARS-CoV-2 infection? FindingsIn this cohort of 55 health care workers previously infected with SARS-CoV-2, we show that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Lack of symptoms and a negative serostatus prior to vaccination leads to immune responses comparable to naive individuals. MeaningOur results support a two-dose primary series requirement for any individual with prior history of asymptomatic SARS-CoV-2 infection.

The REinfection in COVID-19 Estimation of Risk (RECOVER) study: Reinfection and serology dynamics in a cohort of Canadian healthcare workers.

BackgroundUnderstanding the immune response to natural infection by SARS-CoV-2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection. MethodWe conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR-confirmed SARS-CoV-2 infection to : (i) measure the average incidence rate of reinfection and (ii), describe the serological immune response to the primary infection. ResultsWe detected 5 cases of reinfection over 14 months of follow-up, for a reinfection incidence rate of 3.3 per 100 person-years. Median duration of seropositivity was 420 days in symptomatics at primary infection compared to 213 days in asymptomatics (p<0.0001). Other variables associated with prolonged seropositivity for IgG against the spike protein included age 55 and above, obesity, and non-Caucasian ethnicity. SummaryAmong healthcare workers, the incidence of reinfection with SARS-CoV-2 following a primary infection remained rare, although our analysis predates the circulation of the Omicron variant.

Should healthcare workers with SARS-CoV-2 household exposures work? A Cohort Study.

ImportanceDue to high community transmission of the Omicron variant, healthcare workers (HCWs) have been increasingly reporting household exposures to confirmed COVID-19 cases. Quebec (Canada) provincial guidelines required to quarantine these HCWs. Facing the risk of staffing shortages, our hospital decided to allow them to work. ObjectiveTo evaluate the risk for HCWs, who were household contacts, to become positive for COVID-19 by RT-PCR and evaluate the risk of nosocomial COVID-19 transmission. DesignCohort of HCWs with a history of household exposure to a confirmed case of COVID-19. SettingCHU Sainte-Justine, a tertiary care mother and child center in Montreal (QC) Canada ParticipantsConsecutive HCWs who contacted OHS between December 20, 2021 and January 17, 2022 for a history of household exposure to COVID-19. ExposureConfirmed case of COVID-19 in the household Main outcome and measuresThe main outcome was a positive RT-PCR for SARS-CoV-2. Outbreaks and nosocomial cases were identified through daily analysis of COVID-19 cases, by sector and part of the usual Infection Prevention and Control surveillance process. ResultsOverall, 237 of 475 (50%) HCWs who declared a known household contact with a confirmed COVID-19 case remained negative. Of those who became positive, 196 (82.4%) were positive upon initial testing and were quarantined. Only 42 (15%) of 279 HCWs who were allowed to work became positive, a median of 4 days after the initial test. The absence of symptoms at initial evaluation (OR 3.8, 95% CI 2.5-5.7) and having received a third vaccine dose more than 7 days before (OR 1.88, 95% CI 1.3 - 2.8) were associated with an increased odds of remaining negative. There was no outbreak among HCWs and no nosocomial transmission to patients from a HCW that was allowed to work, while a known household contact. Conclusion and relevanceMeasures taken to protect the health care environment from COVID-19 must be cautiously balanced with the risk of staffing shortage. Allowing vaccinated asymptomatic HCWs who are known household contacts of confirmed COVID-19 cases to work is likely a safe alternative, when staff shortage is anticipated.

Evaluation of real-life use of Point-Of-Care Rapid Antigen TEsting for SARS-CoV-2 in schools for outbreak control (EPOCRATES)

AbstractO_ST_ABSBackgroundC_ST_ABSWe evaluated the use of rapid antigen detection tests (RADT) for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in school settings to determine RADTs performance compared to PCR. MethodsIn this real-world, prospective observational cohort study, high-school students and staff were recruited from two high-schools in Montreal (Canada) and followed from January 25th to June 10th, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared to other high schools in the same area. ResultsOverall, 2,099 students and 286 school staff members consented to participate. The overall RADTs specificity varied from 99.8 to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR on D6-7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 57 (72.5%) were secondary to household transmission, 13 (25%) to intra-school transmission and one to community contacts between students in the same school. ConclusionRADT did not perform well as a screening tool in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADT on the spot may avoid subsequent significant exposures in class. Table of Contents SummaryRapid antigen tests were compared to standard PCR to diagnose SARS-CoV-2 infections in high-school students. They performed better in symptomatic individuals. Whats Known on This SubjectRapid antigen detection tests (RADT) are often used to diagnose respiratory pathogens at the point-of-care. Their performance characteristics vary, but they usually have high specificity and moderate sensitivity compared with PCR. What This Study AddsRADT sensitivity ranged from 28.6% in asymptomatic individuals to 83.3% in symptomatic individuals. Return to school after 7 days of quarantine was safe in exposed students. Secondary cases were identified in 28% of classes with an index case.

Saliva-based detection of COVID-19 infection in a real-world setting using reagent-free Raman spectroscopy and machine learning

SignificanceThe primary method of COVID-19 detection is reverse transcription polymerase chain reaction (RT-PCR) testing. PCR test sensitivity may decrease as more variants of concern arise. AimWe aimed to develop a reagent-free way to detect COVID-19 in a real-world setting with minimal constraints on sample acquisition. ApproachWe present a workflow for collecting, preparing and imaging dried saliva supernatant droplets using a non-invasive, label-free technique - Raman spectroscopy - to detect changes in the molecular profile of saliva associated with COVID-19 infection. ResultsUsing machine learning and droplet segmentation, amongst all confounding factors, we discriminated between COVID-positive and negative individuals yielding receiver operating coefficient (ROC) curves with an area under curve (AUC) of 0.8 in both males (79% sensitivity, 75% specificity) and females (84% sensitivity, 64% specificity). Taking the sex of the saliva donor into account increased the AUC by 5%. ConclusionThese findings may pave the way for new rapid Raman spectroscopic screening tools for COVID-19 and other infectious diseases.

Social and racial/ethnic differences in parental willingness to vaccinate children against COVID-19 in Montreal, Canada

BackgroundThe success of current and prospective COVID-19 vaccine campaigns for children and adolescents will in part depend on the willingness of parents to accept vaccination. This study examined social determinants of parental COVID-19 vaccine acceptance and uptake for children and adolescents. MethodsWe used cross-sectional data from an ongoing COVID-19 cohort study in Montreal, Canada and included all parents of 2 to 18-year-olds who completed an online questionnaire between May 18 and June 26, 2021 (n=809). We calculated child age-adjusted prevalence estimates of vaccine acceptance by parental education, race/ethnicity, birthplace, household income, and neighbourhood, and used multinomial logistic regression to estimate adjusted prevalence differences (aPD) and ratios (aPR). Social determinants of vaccine uptake were estimated for the vaccine-eligible sample of 12 to 18 year-olds (n=306). ResultsIntention to vaccinate children against COVID-19 was high, with only 12.4% of parents unlikely to have their child vaccinated. Parents with younger children were less likely to accept vaccination, as were those from lower-income households, racialized groups, and those born outside Canada. The percent of parents whose child was vaccinated or very likely to be vaccinated was 18.4 percentage points lower among those with annual household incomes <$100,000 vs. [≥]$150,000 (95% CI: 10.1 to 26.7). Racialized parents reported greater unwillingness to vaccinate compared to White parents (aPD=10.3; 95% CI: 1.5, 19.1). Vaccine-eligible adolescents from the most deprived neighbourhood were half as likely to be vaccinated compared to those from the least deprived neighbourhood (aPR = 0.48; 95% CI: 0.18 to 0.77). InterpretationThis study identified marked social inequalities in COVID-19 vaccine acceptance and uptake for children and adolescents. Efforts are needed to reach disadvantaged and marginalized populations with tailored strategies that promote informed decision making and facilitate access to vaccination.

Seroprevalence of anti-SARS-CoV-2 antibodies among school and daycare children and personnel: Protocol for a cohort study in Montreal, Canada

BackgroundFurther evidence is needed to understand the contribution of schools and daycares to the spread of COVID-19 in the context of diverse transmission dynamics and continually evolving public health interventions. The Enfants et COVID-19: Etude de seroprevalence (EnCORE) study will estimate the seroprevalence and seroconversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among school and daycare children and personnel. In addition, the study will examine associations between seroprevalence and socio-demographic characteristics and reported COVID-19 symptoms and tests, and investigates changes in health, lifestyle and well-being outcomes. MethodsThis study includes children and personnel from 62 schools and daycares in four neighbourhoods in Montreal, Canada. All children age 2-17 years attending one of the participating schools or daycares and their parents are invited to participate, as well as a sample of personnel members. Participants respond to brief questionnaires and provide blood samples, collected via dried blood spot (DBS), at baseline (October 2020-March 2021) and follow-up (May-June 2021). Questionnaires include socio-demographic and household characteristics, reported COVID-19 symptoms and tests, potential COVID-19 risk factors and prevention efforts, and health and lifestyle information. Logistic regression using generalized estimating equations will be used to estimate seroprevalence and seroconversion, accounting for school-level clustering. DiscussionThe results of the EnCORE study will contribute to our knowledge about SARS-CoV-2 transmission in schools and daycares, which is critical for decisions regarding school attendance and the management of school outbreaks through the remainder of this school year and beyond.