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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.
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BackgroundPaediatric inflammatory multisystem syndrome (PIMS) is a rare but serious condition temporally associated with SARS-CoV-2 infection. Using the Canadian Paediatric Surveillance Program (CPSP), a national surveillance system, we aimed to 1) study the impact of SARS-CoV-2 linkage on clinical and laboratory characteristics, and outcomes in hospitalized children with PIMS across Canada 2) identify risk factors for ICU admission, and 3) establish the minimum national incidence of hospitalizations due to PIMS and compare it to acute COVID-19. MethodsWeekly online case reporting was distributed to the CPSP network of more than 2800 pediatricians, from March 2020 to May 2021. Comparisons were made between cases with respect to SARS-CoV-2 linkage. Multivariable modified Poisson regression was used to identify risk factors for ICU admission and Minimum incidence proportions were calculated. FindingsIn total, 406 PIMS cases were analyzed, of whom 202 (49{middle dot} 8%) had a positive SARS-CoV-2 linkage, 106 (26{middle dot} 1%) had a negative linkage, and 98 (24{middle dot} 1%) had an unknown linkage. The median age was 5{middle dot} 4 years (IQR 2{middle dot} 5-9{middle dot} 8), 60% were male, and 83% had no identified comorbidities. Compared to cases with a negative SARS-CoV-2 linkage, children with a positive SARS-CoV-2 linkage were older (8{middle dot} 1 years [IQR 4{middle dot} 2-11{middle dot} 9] vs. 4{middle dot} 1 years [IQR 1{middle dot} 7-7{middle dot} 7]; p<0{middle dot} 001), had more cardiac involvement (58{middle dot} 8% vs. 37{middle dot} 4%; p<0{middle dot} 001), gastrointestinal symptoms (88{middle dot} 6% vs. 63{middle dot} 2%; p<0{middle dot} 001), and shock (60{middle dot} 9% vs. 16{middle dot} 0%; p<0{middle dot} 001). At-risk groups for ICU admission include children [≥] 6 years and those with a positive SARS-CoV-2 linkage. No deaths were reported. The minimum incidence of PIMS hospitalizations during the study period was 5{middle dot} 6 hospitalizations per 100,000 population <18 years. InterpretationWhile PIMS is rare, almost 1 in 3 hospitalized children required ICU admission and respiratory/hemodynamic support, particularly those [≥] 6 years and with a positive SARS-CoV-2 linkage. FundingFinancial support for the CPSP was received from the Public Health Agency of Canada.
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BackgroundChildren living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada. MethodsWe conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program from April 2020-May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization. FindingsWe identified 544 children hospitalized with SARS-CoV-2 infection, including 60{middle dot}7% with COVID-19-related disease and 39{middle dot}3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1{middle dot}9 years (IQR 0{middle dot}1-13{middle dot}3) and 43{middle dot}0% had chronic comorbid conditions. Severe disease occurred in 29{middle dot}7% of COVID-19-related hospitalizations (n=98/330), most frequently among children aged 2-4 years (48{middle dot}7%) and 12-17 years (41{middle dot}3%). Comorbid conditions associated with severe disease included technology dependence (adjusted risk ratio [aRR] 2{middle dot}01, 95% confidence interval [CI] 1{middle dot}37-2{middle dot}95), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1{middle dot}84, 95% CI 1{middle dot}32-2{middle dot}57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1{middle dot}63, 95% CI 1{middle dot}12-2{middle dot}39). InterpretationWhile severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children. FundingFinancial support for the CPSP was received from the Public Health Agency of Canada.
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ImportanceLongitudinal mass testing using rapid antigen detection tests (RADT) for serial screening of asymptomatic persons has been proposed for preventing SARS-CoV-2 community transmission. The feasibility of this strategy relies on implementation of accurate self-performed RADT testing where people live, work, or attend school. ObjectiveTo quantify the adequacy of serial self-performed SARS-CoV-2 RADT testing in the workplace, in terms of the frequency of correct execution of procedural steps and accurate interpretation of the range of possible RADT results. We compared results using the instructions provided by the manufacturer to those with modified instructions that were informed by the most frequent or most critical errors we observed. DesignRepeated cross-sectional, diagnostic accuracy study performed prospectively in the field. SettingBusinesses in Montreal, Quebec, Canada, with at least 2 active cases of SARS-CoV-2 infection. ParticipantsUntrained, asymptomatic persons in their workplace, not meeting Public Health quarantine criteria. ExposuresA Modified Quick Reference Guide compared to the original manufacturers instructions. Main Outcome(s) and Measure(s)The difference in the proportions of correctly performed procedural steps, and the difference in proportions of correctly interpreted RADT proficiency panel results. The secondary outcome, among subjects with two self-testing visits, compared the second to the first self-test visit using the same measures. ResultsOverall, 1892 tests were performed among 647 subjects. For self-test visit 1, significantly better accuracy in test interpretation was observed using the Modified Quick Reference Guide for weak positive (55.6% vs. 12.3%; 43.3 percentage point improvement, 95% confidence interval [CI] 33.0%-53.8%), positive (89.6% vs. 51.5%; 38.1% difference, 95%CI 28.5%-47.5%), strong positive (95.6% vs. 84.0%; 11.6% improvement, 95%CI 6.8%-16.3%) and invalid (87.3% vs. 77.3%; 10.0% improvement, 95%CI 3.8%-16.3%) tests. Use of the modified guide was associated with smaller, statistically significant, improvements on self-test visit 2. For procedural steps identified as critical for the validity of test results, adherence to procedural testing steps did not differ meaningfully according to instructions provided or reader experience. Conclusions and RelevanceLongitudinal mass RADT testing for SARS-CoV-2 can be accurately self-performed in an intended-use setting; this work provides evidence for how to optimise performance. Key PointsO_ST_ABSQuestioC_ST_ABSDo untrained users correctly perform and interpret the results of SARS-CoV-2 rapid antigen detection tests (RADT) in the workplace, and how can their performance be optimised? FindingsIn this prospective field evaluation of self-performed SARS-CoV-2 RADT in an intended-use setting, we found that the accuracy of RADT interpretation was poor when the manufacturers instructions were used. A Modified Quick Reference Guide yielded significantly better user performance. MeaningLongitudinal mass RADT testing for SARS-CoV-2 can be accurately self-performed in an intended-use setting; this work provides evidence for how to optimise performance.
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ImportanceThere are limited data on outcomes of SARS-CoV-2 infection among infants (<1 year of age). In the absence of approved vaccines for infants, understanding characteristics associated with hospitalization and severe disease from COVID-19 in this age group will help inform clinical management and public health interventions. ObjectiveThe objective of this study was to describe the clinical manifestations, disease severity, and characteristics associated with hospitalization among infants infected with the initial strains of SARS-CoV-2. DesignProspective study of infants with SARS-CoV-2 from April 8th 2020 to May 31st 2021. SettingNational study using the infrastructure of the Canadian Paediatric Surveillance Program, reporting inpatients and outpatients seen in clinics and emergency departments. ParticipantsInfants <1 year of age with microbiologically confirmed SARS-CoV-2 infection. ExposureInfant-level characteristics associated with hospitalization for COVID-19. Main outcomes and MeasuresCases were classified as either: 1) Non-hospitalized patient with SARS-CoV-2 infection; 2) COVID-19-related hospitalization; or 3) non-COVID-19-related hospitalization (e.g., incidentally detected SARS-CoV-2). Case severity was defined as asymptomatic, outpatient care, mild (inpatient care), moderate or severe disease. Multivariable logistic regression was performed to identify characteristics associated with hospitalization. ResultsA total of 531 cases were reported, including 332 (62.5%) non-hospitalized and 199 (37.5%) hospitalized infants. Among hospitalized infants, 141 of 199 infants (70.9%) were admitted because of COVID-19-related illness, and 58 (29.1%) were admitted for reasons other than acute COVID-19. Amongst all cases with SARS-CoV-2 infection, the most common presenting symptoms included fever (66.5%), coryza (47.1%), cough (37.3%) and decreased oral intake (25.0%). In our main analysis, infants with a comorbid condition had higher odds of hospitalization compared to infants with no comorbid conditions (aOR=4.53, 2.06-9.97), and infants <1 month had higher odds of hospitalization then infants aged 1-3 months (aOR=3.78, 1.97-7.26). In total, 20 infants (3.8%) met criteria for severe disease. Conclusions and RelevanceWe describe one of the largest cohorts of infants with SARS-CoV-2 infection. Overall, severe COVID-19 in this age group is uncommon with most infants having mild disease. Comorbid conditions and younger age were associated with COVID-19-related hospitalization amongst infants. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the spectrum of illness, disease severity, and characteristics associated with hospitalization in infants with SARS-CoV-2 infection? FindingsA total of 531 cases were reported to the Canadian Paediatric Surveillance Program, including 332 (62.5%) non-hospitalized and 199 (37.5%) hospitalized infants. In total, 20 infants met criteria for severe disease (3.8%). Infants characteristics associated with admission included age of less than one month and comorbid conditions. MeaningThis study provides data on the spectrum of disease, severity, and characteristics associated with admission due to COVID-19 in infants, which informs clinical management and public health interventions in this specific population.
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BackgroundOur understanding of the global scale of SARS-CoV-2 infection remains incomplete: routine surveillance data underestimates infection and cannot infer on population immunity, there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed SARS-CoV-2 seroprevalence studies, standardized to those described in WHOs Unity protocol for general population seroepidemiological studies, two years into the pandemic, to estimate the extent of population infection and remaining susceptibility. Methods and FindingsWe conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between 2020-01-01 and 2022-05-20. The review protocol is registered with PROSPERO, (CRD42020183634). We included general population cross-sectional and cohort studies meeting an assay quality threshold (90% sensitivity, 97% specificity; exceptions for humanitarian settings). We excluded studies with an unclear or closed population sample frame. Eligible studies - those aligned with the WHO Unity protocol - were extracted and critically appraised in duplicate, with Risk of Bias evaluated using a modified Joanna Briggs Institute checklist. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate under-ascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. The main limitations of our methodology include that some estimates were driven by certain countries or populations being over-represented. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% LMIC) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/sub-national scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1-62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6-28.8] to 86.7% [84.6-88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3-11.0%] to 95.9% [92.6-97.8%] in Europe high-income countries in December 2021). After the emergence of Omicron, infection-induced seroprevalence rose to 47.9% [41.0-54.9%] in EUR HIC and 33.7% [31.6-36.0%] in AMR HIC in March 2022. In 2021 Quarter Three (July to September), median seroprevalence to cumulative incidence ratios ranged from around 2:1 in the Americas and Europe HICs to over 100:1 in Africa (LMICs). Children 0-9 years and adults 60+ were at lower risk of seropositivity than adults 20-29 (p<0.0001 and p=0.005, respectively). In a multivariable model using pre-vaccination data, stringent public health and social measures were associated with lower seroprevalence (p=0.02). ConclusionsIn this study, we observed that global seroprevalence has risen considerably over time and with regional variation, however around 40 % of the global population remains susceptible to SARS-CoV-2 infection. Our estimates of infections based on seroprevalence far exceed reported COVID-19 cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.
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ImportanceChildren are less likely than adults to have severe outcomes from SARS-CoV-2 infection and the corresponding risk factors are not well established. ObjectiveTo identify risk factors for severe disease in symptomatic children hospitalized for PCR-positive SARS-CoV-2 infection. DesignCohort study, enrollment from February 1, 2020 until May 31, 2021 Setting15 childrens hospitals in Canada, Iran, and Costa Rica ParticipantsPatients <18 years of age hospitalized with symptomatic SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C) ExposuresVariables assessed for their association with disease severity included patient demographics, presence of comorbidities, clinical manifestations, laboratory parameters and chest imaging findings. Main Outcomes and MeasuresThe primary outcome was severe disease defined as a WHO COVID-19 clinical progression scale of [≥]6, i.e., requirement of non-invasive ventilation, high flow nasal cannula, mechanical ventilation, vasopressors, or death. Multivariable logistic regression was used to evaluate factors associated with severe disease. ResultsWe identified 403 hospitalizations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Severe disease occurred in 33.8% (102/403). In multivariable analyses, presence of multiple comorbidities (adjusted odds ratio 2.24, 95% confidence interval 1.04-4.81), obesity (2.87, 1.19-6.93), neurological disorder (3.22, 1.37-7.56), anemia, and/or hemoglobinopathy (5.88, 1.30-26.46), shortness of breath (4.37, 2.08-9.16), bacterial and/or viral coinfections (2.26, 1.08-4.73), chest imaging compatible with COVID-19 (2.99, 1.51-5.92), neutrophilia (2.60, 1.35-5.02), and MIS-C diagnosis (3.86, 1.56-9.51) were independent risk factors for severity. Comorbidities, especially obesity (40.9% vs 3.9%, p<0.001), were more frequently present in adolescents [≥]12 years of age. Neurological disorder (3.16, 1.19-8.43) in children <12 years of age and obesity (3.21, 1.15-8.93) in adolescents were the specific comorbidities associated with disease severity in age-stratified adjusted analyses. Sensitivity analyses excluding the 81 cases with MIS-C did not substantially change the identified risk factors. Conclusions and RelevancePediatric risk factors for severe SARS-CoV-2 infection vary according to age and can potentially guide vaccination programs and treatment approaches in children. Key pointsO_ST_ABSQuestionC_ST_ABSWhat are the risk factors for severe disease in children hospitalized for PCR-positive SARS-CoV-2 infection? FindingsIn this multinational cohort study of 403 children, multiple comorbidities, obesity, neurological disorder, anemia, and/or hemoglobinopathy, shortness of breath, bacterial and/or viral coinfections, chest imaging compatible with COVID-19, neutrophilia, and MIS-C diagnosis were independent risk factors for severity. The risk profile and presence of comorbidities differed between pediatric age groups, but age itself was not associated with severe outcomes. MeaningThese results can inform targeted treatment approaches and vaccine programs that focus on patient groups with the highest risk of severe outcomes.
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BackgroundWe aimed to assess the specificity of SARS-CoV-2 antibody detection assays among people with known tissue-borne parasitic infections. MethodsWe tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 Neutralization Antibody Detection Kit, Abbott SARS-CoV-2 IgG assay, and STANDARD Q COVID-19 IgM/IgG Combo Rapid Test) among 559 pre-COVID-19 sera. ResultsThe specificity of assays was 95-98% overall. However, lower specificity was observed among sera from patients with protozoan infections of the reticuloendothelial system, such as human African trypanosomiasis (Abbott Architect; 88% [95%CI 75-95]), visceral leishmaniasis (SD RDT IgG; 80% [95%CI 30-99]), and from patients with recent malaria from a holoendemic area of Senegal (ranging from 91% for Abbott Architect and SD RDT IgM to 98-99% for cPass and SD RDT IgG). For specimens from patients with evidence of past or present helminth infection overall, test specificity estimates were all [≥] 96%. Sera collected from patients clinically suspected of parasitic infections that tested negative for these infections yielded a specificity of 98-100%. The majority (>85%) of false-positive results were positive by only one assay. ConclusionsThe specificity of SARS-CoV-2 serological assays among sera from patients with tissue-borne parasitic infections was below the threshold required for decisions about individual patient care. Specificity is markedly increased by the use of confirmatory testing with a second assay. Finally, the SD RDT IgG proved similarly specific to laboratory-based assays and provides an option in low-resource settings when detection of anti-SARS-CoV-2 IgG is indicated.
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BACKGROUNDSARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We investigated risk factors for severe disease and explored changes in severity over time. METHODSChildren up to 17 years of age admitted March 1, 2020 through March 7th, 2021 to 15 hospitals in Canada, Iran and Costa Rica with confirmed or probable MIS-C were included. Descriptive analysis and comparison by diagnostic criteria, country, and admission date was performed. Adjusted absolute average risks (AR) and risk differences (RD) were estimated for characteristics associated with ICU admission or cardiac involvement. RESULTSOf 232 cases (106 confirmed) with median age 5.8 years, 56% were male, and 22% had comorbidities. ICU admission occurred in 73 (31%) but none died. Median length of stay was 6 days (inter-quartile range 4-9). Children 6 to 12 years old had the highest AR for ICU admission (44%; 95% confidence interval [CI] 34-53). Initial ferritin greater than 500 mcg/L was associated with ICU admission. When comparing cases admitted up to October 31, 2020 to those admitted later, the AR for ICU admission increased from 25% (CI 17-33) to 37% (CI 29-46) and for cardiac involvement from 44% (CI 35-53) to 75% (CI 66-84). Risk estimates for ICU admission in the Canadian cohort demonstrated a higher risk in December 2020-March 2021 compared to March-May 2020 (RD 25%; 95%CI 7-44). INTERPRETATIONMIS-C occurred primarily in previously well children. Illness severity appeared to increase over time. Despite a high ICU admission incidence, most children were discharged within one week.
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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.
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BackgroundA cohort study was conducted to describe and compare the characteristics of SARS-CoV-2 infection in hospitalized children in three countries. MethodsThis was a retrospective cohort of consecutive children admitted to 15 hospitals (13 in Canada and one each in Iran and Costa Rica) up to November 16, 2020. Cases were included if they had SARS-CoV-2 infection or multi-system inflammatory syndrome in children (MIS-C) with molecular detection of SARS-CoV-2 or positive SARS-CoV-2 serology. ResultsOf 211 included cases (Canada N=95; Costa Rica N=84; Iran N=32), 103 (49%) had a presumptive diagnosis of COVID-19 or MIS-C at admission while 108 (51%) were admitted with other diagnoses. Twenty-one (10%) of 211 met criteria for MIS-C. Eighty-seven (41%) had comorbidities. Children admitted in Canada were older than those admitted to non-Canadian sites (median 4.1 versus 2.2 years; p<0.001) and less likely to require mechanical ventilation (3/95 [3%] versus 15/116 [13%]; p<0.05). Sixty-four of 211 (30%) required supplemental oxygen or intensive care unit (ICU) admission and 4 (1.9%) died. Age < 30 days, admission outside Canada, presence of at least one comorbidity and chest imaging compatible with COVID-19 predicted severe or critical COVID-19 (defined as death or need for supplemental oxygen or ICU admission). ConclusionsApproximately half of hospitalized children with confirmed SARS-CoV-2 infection or MIS-C were admitted with other suspected diagnoses. Disease severity was higher at non-Canadian sites. Neonates, children with comorbidities and those with chest radiographs compatible with COVID-19 were at increased risk for severe or critical COVID-19. Main pointsApproximately half of hospitalized children with laboratory confirmed MIS-C or SARS-CoV-2 infection were admitted with another primary diagnoses. The severity of disease was higher in the middle income countries (Costa Rica and Iran) than in Canada.
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BackgroundSARS-CoV-2 surrogate neutralization assays that obviate the need for viral culture offer substantial advantages regarding throughput and cost. The cPass SARS-CoV-2 Neutralization Antibody Detection Kit (Genscript) is the first such commercially available assay, detecting antibodies that block RBD/ACE-2 interaction. We aimed to evaluate cPass to inform its use and assess its added value compared to anti-RBD ELISA assays. MethodsSerum reference panels comprising 205 specimens were used to compare cPass to plaque-reduction neutralization test (PRNT) and a pseudotyped lentiviral neutralization (PLV) assay for detection of neutralizing antibodies. We assessed the correlation of cPass with an ELISA detecting anti-RBD IgG, IgM, and IgA antibodies at a single timepoint and across intervals from onset of symptoms of SARS-CoV-2 infection. ResultsCompared to PRNT-50, cPass sensitivity ranged from 77% - 100% and specificity was 95% - 100%. Sensitivity was also high compared to the pseudotyped lentiviral neutralization assay (93% [95%CI 85-97]), but specificity was lower (58% [95%CI 48-67]). Highest agreement between cPass and ELISA was for anti-RBD IgG (r=0.823). Against the pseudotyped lentiviral neutralization assay, anti-RBD IgG sensitivity (99% [95%CI 94-100]) was very similar to that of cPass, but overall specificity was lower (37% [95%CI 28-47]). Against PRNT-50, results of cPass and anti-RBD IgG were nearly identical. ConclusionsThe added value of cPass compared to an IgG anti-RBD ELISA was modest.
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BackgroundMany studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making. MethodsIn this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634. ResultsWe identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4-8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6 % in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (p<0.001). National studies had lower seroprevalence estimates than regional and local studies (p<0.001). Compared to Caucasian persons, Black persons (prevalence ratio [RR] 3.37, 95% CI 2.64-4.29), Asian persons (RR 2.47, 95% CI 1.96-3.11), Indigenous persons (RR 5.47, 95% CI 1.01-32.6), and multi-racial persons (RR 1.89, 95% CI 1.60-2.24) were more likely to be seropositive. Seroprevalence was higher among people ages 18-64 compared to 65 and over (RR 1.27, 95% CI 1.11-1.45). Health care workers in contact with infected persons had a 2.10 times (95% CI 1.28-3.44) higher risk compared to health care workers without known contact. There was no difference in seroprevalence between sex groups. Seroprevalence estimates from national studies were a median 18.1 times (IQR 5.9-38.7) higher than the corresponding SARS-CoV-2 cumulative incidence, but there was large variation between Global Burden of Disease regions from 6.7 in South Asia to 602.5 in Sub-Saharan Africa. Notable methodological limitations of serosurveys included absent reporting of test information, no statistical correction for demographics or test sensitivity and specificity, use of non-probability sampling and use of non-representative sample frames. DiscussionMost of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response. FundingPublic Health Agency of Canada through the COVID-19 Immunity Task Force.
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BackgroundEvidence-based infection control strategies are needed for healthcare workers (HCWs) following high-risk exposure to SARS-CoV-2. This study evaluated the negative predictive value (NPV) of a home-based 7-day infection control strategy. MethodsHCWs advised by their Infection Control or Occupational Health officer to self-isolate due to a high-risk SARS-CoV-2 exposure were enrolled between May-September 2020. The strategy consisted of symptom-triggered nasopharyngeal SARS-CoV-2 RNA testing from day 0-6 post exposure, followed by standardized home-based nasopharyngeal swab and saliva testing on day 7. The NPV of this strategy was calculated for i) clinical COVID-19 diagnosis from day 8-14 post exposure, and for ii) asymptomatic SARS-CoV-2 detected by standardized nasopharyngeal swab and saliva specimens collected at days 9-10 and 14 post exposure. Interim results are reported in the context of a second wave threatening this essential workforce. ResultsAmong 30 HCWs enrolled to date (age 31{+/-}9 years, 24 [80.0%] female), 3 were diagnosed with COVID-19 by day 14 post exposure (secondary attack rate 10.0%), with all cases detected by the 7-day infection control strategy: NPV for subsequent clinical COVID-19 or asymptomatic SARS-CoV-2 detection by day 14 was 100.0% (95%CI: 93.1-100.0%). InterpretationAmong HCWs with high-risk exposure to SARS-CoV-2, a home-based 7-day infection control strategy may have a high NPV for subsequent COVID-19 and asymptomatic SARS-CoV-2 detection. While ongoing data collection and data sharing are needed to improve the precision of the estimated NPV, we report interim results to inform infection control strategies in light of a second wave threatening this essential workforce.