Differential Adaptive Immune Responses Following SARS-CoV-2 Infection in Children Compared to Adults (preprint)

BackgroundSARS-CoV-2 infection elicits distinct clinical features in children and adults. Profiling the adaptive immune response following infection in children is essential to better understand and characterize these differences. MethodsHumoral and cell-mediated immune responses from unvaccinated pediatric and adult participants were analyzed following asymptomatic or mild non-Omicron SARS-CoV-2 infection. Levels of IgG and IgA targeting spike (S), receptor-binding domain (RBD), and nucleocapsid (N) proteins of SARS-CoV-2 were measured, while neutralizing antibody (nAb) titers were assessed against three viral strains (Wuhan, Omicron BA.1 and BA.4/BA.5). Specific T-cell memory responses were investigated by quantifying interferon-gamma (IFN-{gamma}) secreting cells after stimulation with ancestral and variant strains of SARS-CoV-2, and seasonal human {beta}- coronaviruses (HCoV)-OC43 and -HKU1. ResultsThe study comprised 28 children (3 to 17 [median=10] years old) and 28 adults (19 to 62 [median=42]). At a mean time of seven months ({+/-} 2.8 months) after SARS-CoV-2 infection, children and adults mounted comparable antibody levels against S and RBD, as well as similar neutralization capacity. However, children displayed a weaker cellular memory response to SARS- CoV-2 than adults, with a median of 88 [28-184] spot forming units per million of PBMCs in children compared to 208 [141-340] in adults (***, P < .001). In children, the level of IFN-{gamma} secreting cells in response to SARS-CoV-2 corresponds to that of seasonal coronaviruses. ConclusionLong-term memory T-cell responses to SARS-CoV-2 are enhanced in adults compared to children who demonstrate equivalent responses to SARS-CoV-2 and other HCoV. HIGHLIGHTSO_LIChildren infected with SARS-CoV-2 show comparable binding and neutralizing antibody levels as adults seven months after infection. C_LIO_LIThere are notable differences in the intensity of the T-cell response following SARS-CoV- 2 infection between children and adults. C_LIO_LIChildren have more pronounced T-cell immunodominance towards the spike versus non- spike proteins compared to adults at seven months post-infection C_LIO_LIIn contrast, T-cell responses to SARS-CoV-2 are globally reduced in children compared to adults but are alike to other seasonal {beta}-coronaviruses. C_LI

Omicron Breakthrough Infection Elicits Superior Humoral and Mucosal Immune Responses to SARS-CoV-2 Variants than an Intramuscular Booster Dose (preprint)

Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT. Our results show that mild BT infection induces cell-mediated immune responses to variants comparable to an intramuscular vaccine booster dose. In contrast, BT subjects had higher salivary IgG and IgA levels against the Omicron Spike and enhanced reactivity to the ancestral Spike for the IgA isotype, which also reacted with SARS-CoV-1. Serum neutralizing antibody levels against the ancestral strain and the variants were also higher after BT infection. Our results support the need for mucosal vaccines to emulate the enhanced mucosal and humoral immunity induced by Omicron without exposing individuals to the risks associated with SARS-CoV-2 infection.

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 (preprint)

Importance: Repeated 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. Objective: To use serological testing to assess the prevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies in children and adolescents in Montreal, Canada. Design: This 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. Setting: Population-based sample. Participants: Children and adolescents aged 2 to 17 years in Montreal, Canada. Exposure: Potential exposure to SARS-CoV-2. Main Outcomes and Measures: Participants 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. Results: The 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 5.8% (95% CI 4.8-7.1), which increased to 10.5% and 10.9% for the respective follow-ups (95% CI 8.6-12.7; 95% CI 8.8-13.5). The overall average crude rate of seroconversion over the study period was 12.7 per 100 person-years (95% CI 10.9-14.5). 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 Relevance: The 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.

PRevention of COVID-19 with Oral Vitamin D supplemental Therapy in Essential healthCare Teams (PROTECT): Ancillary study of a randomised controlled trial (preprint)

Background: The study objectives were to ascertain the efficacy of vitamin D supplementation in rapidly increasing serum vitamin D and of implementation of a hybrid (virtual and in-person) trial. Methods In a randomised triple-blind controlled trial, healthcare workers were allocated to receive an oral bolus of 100,000 IU with 10,000 IU/week vitamin D 3 or placebo. The co-primary outcomes of this ancillary study were the change from baseline in serum 25-hydroxyvitamin D [(Δ) 25(OH)D] and proportion with vitamin D sufficiency (25(OH)D ≥ 75nmol/L), at endpoint. Adherence to supplements and procedures as well as adverse event rates were documented. Results Thirty-four (19 intervention, 15 control) subjects were randomised, with 28 (41%) virtual visits. After 44.78 ± 11.00 days from baseline, a significant adjusted group difference of 44.2 (34.7, 53.8) nmol/L was observed in the Δ 25(OH)D (95%CI) in favor of supplementation; 77.8% of intervention, and 13.3% of control, patients were vitamin D sufficient (OR:6.11, 95%CI:1.6, 22.9 ). The adherence to intervention was 94.7% in the intervention and 100% in the control groups. Irrespective of visit type, high adherence was observed in sampling procedures and completion of fortnightly online questionnaire. No adverse events attributable to vitamin D were reported. Conclusion The vitamin D supplementation rapidly and safely raised 25(OH)D levels to sufficient levels for a biological effect. Similarly high adherence to study procedures was observed with virtual and in-person participation. Trial registration: This trial was registered at https://clinicaltrials.gov on July 23, 2020 (#NCT04483635)

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

ABSTRACT Importance Public 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. Objective Evaluate the immune response to COVID-19 mRNA vaccines in healthcare workers (HCWs) who recovered from a SARS-CoV-2 infection. Design Multicentric 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. Participants Unvaccinated 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 naïve controls. Exposure Vaccination 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-γ 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. Results None of the naïve 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 naïve individuals, with significantly weaker responses than those who were symptomatic during infection. Conclusions and Relevance Individuals 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 naïve 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 Question Is a single dose of COVID-19 mRNA vaccine sufficient to induce robust immune responses in individuals with prior SARS-CoV-2 infection? Findings In 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 naïve individuals. Meaning Our 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. (preprint)

Background : Understanding 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. Method : We 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. Results : We 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. Summary : Among 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. (preprint)

Due to high community transmission of the Omicron variant, healthcare workers (HCWs) have been increasingly reporting household exposures to confirmed COVID19 cases. Quebec (Canada) provincial guidelines required to quarantine these HCWs. Facing the risk of staffing shortages, our hospital decided to allow them to work. Objective: To evaluate the risk for HCWs, who were household contacts, to become positive for COVID19 and evaluate the risk of nosocomial COVID19 transmission. Design: Cohort of consecutive HCWs with a history of household exposure to a confirmed case of COVID19 who contacted OHS at CHU Sainte-Justine, Montreal (QC) Canada between December 20, 2021 and January 17, 2022 for a history of household exposure to COVID19. Exposure: Confirmed case of COVID19 in the household Main outcome and measures: The 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. Results: Overall, 237 of 475 (50%) HCWs who declared a known household contact with a confirmed COVID19 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 relevance: Measures taken to protect the health care environment from COVID19 must be cautiously balanced with the risk of staffing shortage. Allowing vaccinated asymptomatic HCWs who are known household contacts of confirmed COVID19 cases to work is likely a safe alternative, when staff shortage is anticipated.

The COVID-19 pandemic impacted maternal mental health differently depending on pregnancy status and trimester of gestation (preprint)

Introduction: We aimed to measure the impact of the COVID-19 pandemic on maternal mental health, stratifying on pregnancy status, trimester of gestation, and pandemic period/wave. Methods: : Pregnant persons and persons who delivered in Canada during the pandemic, >18 years, were recruited, and data were collected using a web-based strategy. The current analysis includes data on persons enrolled between 06/2020-08/2021. Maternal sociodemographic indicators, mental health measures (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7), stress) were self-reported. Maternal mental health in pregnant women (stratified by trimester, and pandemic period/wave at recruitment) was compared with mental health of women who had delivered; determinants of severe depression were identified with multivariate logistic regression models. Results: : 2,574 persons were pregnant and 626 had already delivered at recruitment. Participants who had delivered had significantly higher mean depressive symptom scores compared to those pregnant at recruitment (9.1 (SD, 5.7) vs. 8.4 (SD, 5.3), p=0.009). Among those who were pregnant at recruitment, depressive symptoms were significantly higher in women recruited in their third trimester, and those recruited during the 2 nd wave of the pandemic. Maternal anxiety (aOR 1.51; 95%CI 1.44-1.59) and stress (aOR 1.35; 95%CI 1.24-1.48) were the most significant predictors of severe maternal depression (EDPS˃13) in pregnancy. Conclusion: The COVID-19 pandemic had a significant impact on maternal depression during pregnancy and in the post-partum period. Given that gestational depression/anxiety/stress have been associated with preterm birth and childhood cognitive problems, it is essential to continue following women/children, and develop strategies to reduce COVID-19’s longer-term impact.

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

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 (preprint)

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.

Seroprevalence of Anti-SARS-CoV-2 Antibodies Among School and Daycare Children: Baseline Results From a Cohort Study in Montreal, Canada (preprint)

Background: Montreal was one of the highest COVID-19 burdened cities in Canada during the first and second waves of the pandemic. We estimated the seroprevalence of SARS-CoV-2 in children and teenagers in four neighbourhoods of Montreal, Canada.Methods: All children attending selected schools and daycares within the four neighbourhoods were invited to participate in the study. Study participation included an online questionnaire that parents completed, followed by at-home dried blood spot (DBS) collection. Serological results were analyzed using a research-based ELISA assay. Statistical analyses included multivariable logistic regression models to calculate average marginal effects and robust standard errors to account for clustering by school or daycare. Several different sociodemographic differences were examined between the seronegative and seropositive children.Findings: There were 30 daycares, 22 primary schools, and 11 secondary schools that participated in the study with 1,632 participants having provided a DBS sample that was of sufficient quality for the serological analysis. The average seroprevalence was 5·8% (95%CI 4·6 to 7·0) but increased over time from 3·2% (95% CI 0·7 to 5·8) in October-November 2020 to 8.4% (95% CI 4·4 to 12·4) in March-April 2021. The children of visible minority parents were nearly twice as likely to be seropositive as children of non-visible minority parents (1·93, 95%CI 1·11 to 2·75). Interpretation: Our results provide a benchmark of the seroprevalence status in Canadian children and provide further evidence of COVID-19 inequities. It will be important to continue monitoring the serological status of children, particularly in the context of new COVID-19 variants of concern and in the absence of mass vaccination campaigns targeting young children.Funding Information: Public Health Agency of Canada through the COVID-19 Immunity Task Force.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: All participants provided informed consent for the survey and ethics approval was received from the research ethics boards of the Université de Montréal and the Centre Hospitalier Universitaire Sainte-Justine.

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

Little is known about the extent of social or racial/ethnic differences in parental hesitancy around COVID-19 vaccination for their children. Using cross-sectional data from an ongoing cohort study in Montreal, Canada, we examined willingness to vaccinate children according to level of education, neighbourhood, and visible minority status. Parents of children aged 2-17 completed a vaccine hesitancy module of an online questionnaire and we used logistic regression to estimate associations between vaccine willingness and education, neighbourhood, and visible minority status. Of the 380 parents who completed the module, 61% were very likely, 25% somewhat likely, 9.2% somewhat unlikely, and 4.5% very unlikely to have their child vaccinated against COVID-19. Visible minority status was strongly associated with willingness to vaccinate, while neighbourhood and level of education were not significantly associated. Further research is needed to quantify these differences on a larger scale and to better understand why certain communities have lower vaccination intention in order to develop tailored strategies to promote vaccine acceptance and uptake.

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

Background: Further 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. Methods: This 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. Discussion: The 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. Keywords SARS-CoV-2; COVID-19; Children; School; Serology; Protocol; Canada

Impact of the COVID-19 Pandemic on Maternal Mental Health During Pregnancy: The CONCEPTION Study – Phase I (preprint)

Background: Mental health regional differences during pregnancy through the COVID-19 pandemic are understudied. The first phase of CONCEPTION cohort aims to compare country-specific mental health status in pregnant women following the start of the pandemic.Methods: Pregnant women, >18 years were recruited, and data collected using a web-based strategy. Although Canadian women were primarily targeted, pregnant women worldwide were eligible. The current analysis includes data on women enrolled between 06/2020-11/2020. Self-reported data included COVID-19 testing/diagnosis, mental health measures (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7)), prenatal care/birth plan changes. We compared maternal mental health stratifying on country/continents of residence; and identified determinants of mental health with multivariable linear regression models.Findings: Of 2,109 pregnant women recruited (mean gestational age, 24·7 weeks (SD 9·7)), 1,932 were from Canada, 48 the United States (US), 73 Europe, 35 Africa, and 21 Asia/Oceania. Among the 226 pregnant women who were tested for SARS-CoV-2, 26 were positive (11·5% test positivity rate); COVID-19 prevalence was 1·2% (26/2,109). Mean depressive symptom scores were lower in Canada (EPDS 8·2, SD 5·2) compared to the US (EPDS 10·5, SD 4·8) and Europe (EPDS 10·4, SD 6·5) (p<0·05). Maternal anxiety, stress, decreased income and access to health care due to the pandemic were independently increasing maternal depression. Mean anxiety symptoms were higher in the US (GAD-7 6·5, SD 4·3) than Canada (GAD-7 4·3, SD 3·8) (p<0·05). Maternal depression, stress, and earlier recruitment during the pandemic were independently associated with increased maternal anxiety.Interpretation: In this first international study on the impact of the COVID-19 pandemic, CONCEPTION has shown significant country/continent-specific variations in depression and anxiety during pregnancy. Given that gestational depression/anxiety have been associated with preterm birth and childhood cognitive problems, strategies are needed to reduce COVID-19’s mental health burden. Funding: Faculty of Pharmacy, Université de Montréal, Canada.Declaration of Interests: We declare no competing interests.Ethics Approval Statement: This study was approved by the CHU Sainte-Justine's Research Ethics Committee, which autorized worldwide recruitment of subjects.

Navigating Inequities: A Roadmap out of the Pandemic (preprint)

The COVID-19 pandemic has exposed social inequities that rival biological inequities in disease exposure and severity. Merely identifying some inequities without understanding all of them can lead to harmful misrepresentations and deepening disparities. Applying an ‘equity lens’ to bring inequities into focus without a vision to extinguish them is short-sighted. Interventions to address inequities should be as diverse as the pluralistic populations experiencing them. We present the first validated equity framework applied to COVID-19 that sheds light on the full spectrum of health inequities, navigates their sources and intersections, and directs ethically just interventions. The Equity Matrix also provides a comprehensive map to guide surveillance and research in order to unveil epidemiological uncertainties of novel diseases like COVID-19, recognising that inequities may exist where evidence is currently insufficient. Successfully applied to vaccines in recent years, this tool has resulted in the development of clear, timely and transparent guidance with positive stakeholder feedback on its comprehensiveness, relevance and appropriateness. Informed by evidence and experience from other vaccine-preventable diseases, this Equity Matrix could be valuable to countries across the social gradient to slow the spread of SARS-CoV-2 by abating the spread of inequities. In the race to SARS-CoV-2 vaccines, this urgently needed roadmap can effectively and efficiently steer global leadership towards equitable allocation with diverse strategies for diverse inequities. Such a roadmap has been absent from discussions on managing the COVID-19 pandemic, and is critical for our passage out of it.