Determinants of COVID-19 vaccine hesitancy among students and parents in Sentinel Schools Network of Catalonia, Spain.

Vaccine hesitancy is defined as a delay in acceptance of vaccines despite its availability, caused by many determinants. Our study presents the key reasons, determinants and characteristics associated with COVID-19 vaccine acceptability among students over 16 years and parents of students under 16 years and describe the COVID-19 vaccination among students in the settings of sentinel schools of Catalonia, Spain. This is a cross-sectional study that includes 3,383 students and the parents between October 2021 and January 2022. We describe the student's vaccination status and proceed a univariate and multivariate analysis using a Deletion Substitution Addition (DSA) machine learning algorithm. Vaccination against COVID-19 reached 70.8% in students under 16 years and 95.8% in students over 16 years at the end of the study project. The acceptability among unvaccinated students was 40.9% and 20.8% in October and January, respectively, and among parents was proportionally higher among students aged 5-11 (70.2%) in October and aged 3-4 (47.8%) in January. The key reason to not vaccinate themselves, or their children, were concern about side effects, insufficient research about the effect of the vaccine in children, rapid development of vaccines, necessity for more information and previous infection by SARS-CoV-2. Several variables were associated with refusal end hesitancy. For students, the main ones were risk perception and use of alternative therapies. For parents, the age of students, sociodemographic variables, socioeconomic impact related to the pandemic, and use of alternative therapies were more evident. Monitoring vaccine acceptance and refusal among children and their parents has been important to understand the interaction between different multilevel determinants and we hope it will be useful to improve public health strategies for future interventions in this population.

Multisystem inflammatory syndrome in children and SARS-CoV-2 variants: a two-year ambispective multicentric cohort study in Catalonia, Spain.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe disease temporarily related to SARS-CoV-2. We aimed to describe the epidemiological, clinical, and laboratory findings of all MIS-C cases diagnosed in children < 18 years old in Catalonia (Spain) to study their trend throughout the pandemic. This was a multicenter ambispective observational cohort study (April 2020-April 2022). Data were obtained from the COVID-19 Catalan surveillance system and from all hospitals in Catalonia. We analyzed MIS-C cases regarding SARS-CoV-2 variants for demographics, symptoms, severity, monthly MIS-C incidence, ratio between MIS-C and accumulated COVID-19 cases, and associated rate ratios (RR). Among 555,848 SARS-CoV-2 infections, 152 children were diagnosed with MIS-C. The monthly MIS-C incidence was 4.1 (95% CI: 3.4-4.8) per 1,000,000 people, and 273 (95% CI: 230-316) per 1,000,000 SARS-CoV-2 infections (i.e., one case per 3,700 SARS-CoV-2 infections). During the Omicron period, the MIS-C RR was 8.2 (95% CI: 5.7-11.7) per 1,000,000 SARS-CoV-2 infections, which was significantly lower (p < 0.001) than that for previous variant periods in all age groups. The median [IQR] age of MIS-C was 8 [4-11] years, 62.5% male, and 80.2% without comorbidities. Common symptoms were gastrointestinal findings (88.2%) and fever > 39 °C (81.6%); nearly 40% had an abnormal echocardiography, and 7% had coronary aneurysm. Clinical manifestations and laboratory data were not different throughout the variant periods (p > 0.05).  Conclusion: The RR between MIS-C cases and SARS-CoV-2 infections was significantly lower in the Omicron period for all age groups, including those not vaccinated, suggesting that the variant could be the main factor for this shift in the MISC trend. Regardless of variant type, the patients had similar phenotypes and severity throughout the pandemic. What is Known: • Before our study, only two publications investigated the incidence of MIS-C regarding SARS-CoV-2 variants in Europe, one from Southeast England and another from Denmark. What is New: • To our knowledge, this is the first study investigating MIS-C incidence in Southern Europe, with the ability to recruit all MIS-C cases in a determined area and analyze the rate ratio for MIS-C among SARS-CoV-2 infections throughout variant periods. • We found a lower rate ratio of MISC/infections with SARS-CoV-2 in the Omicron period for all age groups, including those not eligible for vaccination, suggesting that the variant could be the main factor for this shift in the MISC trend.

Unravelling the role of the mandatory use of face covering masks for the control of SARS-CoV-2 in schools: a quasi-experimental study nested in a population-based cohort in Catalonia (Spain).

OBJECTIVE: To assess the effectiveness of mandatory use of face covering masks (FCMs) in schools during the first term of the 2021-2022 academic year. DESIGN: A retrospective population-based study. SETTING: Schools in Catalonia (Spain). POPULATION: 599 314 children aged 3-11 years attending preschool (3-5 years, without FCM mandate) and primary education (6-11 years, with FCM mandate). STUDY PERIOD: From 13 September to 22 December 2021 (before Omicron variant). INTERVENTIONS: A quasi-experimental comparison between children in the last grade of preschool (5 years old), as a control group, and children in year 1 of primary education (6 years old), as an interventional group. MAIN OUTCOME MEASURES: Incidence of SARS-CoV-2, secondary attack rates (SARs) and effective reproductive number (R*). RESULTS: SARS-CoV-2 incidence was significantly lower in preschool than in primary education, and an increasing trend with age was observed. Six-year-old children showed higher incidence than 5 year olds (3.54% vs 3.1%; OR 1.15 (95% CI 1.08 to 1.22)) and slightly lower but not statistically significant SAR (4.36% vs 4.59%; incidence risk ratio 0.96 (95% CI 0.82 to 1.11)) and R* (0.9 vs 0.93; OR 0.96 (95% CI 0.87 to 1.09)). Results remained consistent using a regression discontinuity design and linear regression extrapolation approaches. CONCLUSIONS: We found no significant differences in SARS-CoV-2 transmission due to FCM mandates in Catalonian schools. Instead, age was the most important factor in explaining the transmission risk for children attending school.

Multisystem Inflammatory Syndrome in Children in Western Countries? Decreasing Incidence as the Pandemic Progresses?: An Observational Multicenter International Cross-sectional Study.

BACKGROUND: SARS-CoV-2 variations as well as immune protection after previous infections and/or vaccination may have altered the incidence of multisystemic inflammatory syndrome in children (MIS-C). We aimed to report an international time-series analysis of the incidence of MIS-C to determine if there was a shift in the regions or countries included into the study. METHODS: This is a multicenter, international, cross-sectional study. We collected the MIS-C incidence from the participant regions and countries for the period July 2020 to November 2021. We assessed the ratio between MIS-C cases and COVID-19 pediatric cases in children <18 years diagnosed 4 weeks earlier (average time for the temporal association observed in this disease) for the study period. We performed a binomial regression analysis for 8 participating sites [Bogotá (Colombia), Chile, Costa Rica, Lazio (Italy), Mexico DF, Panama, The Netherlands and Catalonia (Spain)]. RESULTS: We included 904 cases of MIS-C, among a reference population of 17,906,432 children. We estimated a global significant decrease trend ratio in MIS-C cases/COVID-19 diagnosed cases in the previous month ( P < 0.001). When analyzing separately each of the sites, Chile and The Netherlands maintained a significant decrease trend ( P < 0.001), but this ratio was not statistically significant for the rest of sites. CONCLUSIONS: To our knowledge, this is the first international study describing a global reduction in the trend of the MIS-C incidence during the pandemic. COVID-19 vaccination and other factors possibly linked to the virus itself and/or community transmission may have played a role in preventing new MIS-C cases.

The COVID-19 Sentinel Schools Network of Catalonia (CSSNC) project: Associated factors to prevalence and incidence of SARS-CoV-2 infection in educational settings during the 2020-2021 academic year.

The Sentinel Schools project was designed to monitor and evaluate the epidemiology of COVID-19 in Catalonia, gathering evidence for health and education policies to inform the development of health protocols and public health interventions to control of SARS-CoV-2 infection in schools. The aim of this study was to estimate the prevalence and incidence of SARS-CoV-2 infections and to identify their determinants among students and staff during February to June in the academic year 2020-2021. We performed two complementary studies, a cross-sectional and a longitudinal component, using a questionnaire to collect nominal data and testing for SARS-CoV-2 detection. We describe the results and perform a univariate and multivariate analysis. The initial crude seroprevalence was 14.8% (95% CI: 13.1-16.5) and 22% (95% CI: 18.3-25.8) for students and staff respectively, and the active infection prevalence was 0.7% (95% CI: 0.3-1) and 1.1% (95% CI: 0.1-2). The overall incidence for persons at risk was 2.73 per 100 person-month and 2.89 and 2.34 per 100 person-month for students and staff, respectively. Socioeconomic, self-reported knowledge, risk perceptions and contact pattern variables were positively associated with the outcome while sanitary measure compliance was negatively associated, the same significance trend was observed in multivariate analysis. In the longitudinal component, epidemiological close contact with SARS-CoV-2 infection was a risk factor for SARS-CoV-2 infection while the highest socioeconomic status level was protective as was compliance with sanitary measures. The small number of active cases detected in these schools suggests a low transmission among children in school and the efficacy of public health measures implemented, at least in the epidemiological scenario of the study period. The major contribution of this study was to provide results and evidence that help analyze the transmission dynamic of SARS-CoV-2 and evaluate the associations between sanitary protocols implemented, and measures to avoid SARS-CoV-2 spread in schools.

Health and Vaccination Status of Unaccompanied Minors After Arrival in a European Border Country: A Cross-sectional Study (2017-2020).

BACKGROUND: Unaccompanied and separated children (UASC) are a high-risk group for infectious diseases and information on their vaccination status is scarce. Different approaches are used to screen newly arrived minors in Europe. The aim of this study was to describe the health status and serological protection against different vaccine-preventable diseases among UASC to inform public health decision-making. METHODS: Retrospective study of all UASC seen at an international health reference center in Barcelona (Spain) between January 2017 and February 2020. Screening results were analyzed using binary logistic regression with adjustment for symptoms, geographic origin, and time since arrival. RESULTS: We studied 289 UASC (88.9% males; median age, 17 years). At least one infection was diagnosed in 136 minors (47.1%). There was a high prevalence of intestinal parasites (22.8%), latent tuberculosis infection (22.5%), and hepatitis B (5.2%), even in asymptomatic individuals, and especially among UASC from sub-Saharan Africa (odds ratio, 2.5; 95% confidence interval, 1.5-4.0, P < 0.001). We did not observe a significant association between clinical symptoms and the presence of infection or differences in the prevalence of different infections according to number of months since arrival. Protection against hepatitis B virus (36%), measles (80%), and varicella (83%) was suboptimal. CONCLUSIONS: Our results highlight the importance of screening and vaccination programs for UASC arriving in Europe, especially border countries. Protocols should be adjusted according to geographic origin. Absence of symptoms does not necessarily rule out infection, highlighting the importance of screening in asymptomatic minors. These programs are a public health priority and should not be neglected during the current COVID-19 pandemic.

Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Children with a History of Multisystem Inflammatory Syndrome in Children: An International Survey.

The optimal severe acute respiratory syndrome coronavirus 2 vaccine strategy for patients with a history of multisystem inflammatory syndrome in children (MIS-C) is unclear. We performed an international survey (32 countries) and found substantial variations in vaccine policies. Respondents did not report relapses of MIS-C or other severe inflammatory side effects after severe acute respiratory syndrome coronavirus 2 vaccination in 273 patients with a history of MIS-C.

Comparison of pneumonia features in children caused by SARS-CoV-2 and other viral respiratory pathogens.

BACKGROUND: Pneumonia is a frequent manifestation of coronavirus disease 2019 (COVID-19) in hospitalized children. METHODS: The study involved 80 hospitals in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spanish Pediatric National Cohort. Participants were children <18 years, hospitalized with SARS-CoV-2 community-acquired pneumonia (CAP). We compared the clinical and radiological characteristics of SARS-CoV-2-associated CAP with CAP due to other viral etiologies from ValsDance (retrospective) cohort. RESULTS: In total, 151 children with SARS-CoV-2-associated CAP and 138 with other viral CAP were included. Main clinical features of SARS-CoV-2-associated CAP were cough, fever, or dyspnea. Lymphopenia was found in 43% patients and 15% required admission to the pediatric intensive care unit (PICU). Chest X-ray revealed condensation (42%) and other infiltrates (58%). Compared with CAP from other viral pathogens, COVID-19 patients were older, with lower C-reactive protein (CRP) levels, less wheezing, and greater need of mechanical ventilation (MV). There were no differences in the use of continuous positive airway pressure (CPAP) or HVF, or PICU admission between groups. CONCLUSION: SARS-CoV-2-associated CAP in children presents differently to other virus-associated CAP: children are older and rarely have wheezing or high CRP levels; they need less oxygen but more CPAP or MV. However, several features overlap and differentiating the etiology may be difficult. The overall prognosis is good.

Age-dependency of the Propagation Rate of Coronavirus Disease 2019 Inside School Bubble Groups in Catalonia, Spain.

BACKGROUND: We analyzed contagions of coronavirus disease 2019 inside school bubble groups in Catalonia, Spain, in the presence of strong nonpharmaceutical interventions from September to December 2020. More than 1 million students were organized in bubble groups and monitored and analyzed by the Health and the Educational departments. METHODS: We had access to 2 data sources, and both were employed for the analysis, one is the Catalan school surveillance system and the other of the educational department. As soon as a positive index case is detected by the health system, isolation is required for all members of the bubble group, in addition to a mandatory proactive systematic screening of each individual. All infected cases are reported. It permits the calculation of the average reproductive number (R*), corresponding to the average number of infected individuals per index case. RESULTS: We found that propagation inside of the bubble group was small. Among 75% index cases, there was no transmission to other members in the classroom, with an average R* across all ages inside the bubble of R* = 0.4. We found a significant age trend in the secondary attack rates, with the R* going from 0.2 in preschool to 0.6 in high school youth. CONCLUSIONS: The secondary attack rate depends on the school level and therefore on the age. Super-spreading events (outbreaks of 5 cases or more) in childhood were rare, only occurring in 2.5% of all infections triggered from a pediatric index case.

QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs☆☆☆ Evolución del intervalo QTc en pacientes con infección SARS-COV-2 tratados con farmacos antivirales

Introduction Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. Patients and methods Paediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h of treatment and after 72 h. Results Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March–July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11;36.4%) and immunosuppression (3/11;27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs 416.5 ms (29.4), (P = .716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11;72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms [IQR 48.7] (P = .062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms;treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. Conclusions The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc > 500 ms.

QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs.

INTRODUCTION: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. PATIENTS AND METHODS: Paediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h of treatment and after 72 h. RESULTS: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March-July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs 416.5 ms (29.4), (P = .716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms [IQR 48.7] (P = .062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. CONCLUSIONS: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc > 500 ms.

Symptom-Based Predictive Model of COVID-19 Disease in Children.

BACKGROUND: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is neither always accessible nor easy to perform in children. We aimed to propose a machine learning model to assess the need for a SARS-CoV-2 test in children (<16 years old), depending on their clinical symptoms. METHODS: Epidemiological and clinical data were obtained from the REDCap® registry. Overall, 4434 SARS-CoV-2 tests were performed in symptomatic children between 1 November 2020 and 31 March 2021, 784 were positive (17.68%). We pre-processed the data to be suitable for a machine learning (ML) algorithm, balancing the positive-negative rate and preparing subsets of data by age. We trained several models and chose those with the best performance for each subset. RESULTS: The use of ML demonstrated an AUROC of 0.65 to predict a COVID-19 diagnosis in children. The absence of high-grade fever was the major predictor of COVID-19 in younger children, whereas loss of taste or smell was the most determinant symptom in older children. CONCLUSIONS: Although the accuracy of the models was lower than expected, they can be used to provide a diagnosis when epidemiological data on the risk of exposure to COVID-19 is unknown.

Clinical spectrum of COVID-19 and risk factors associated with severity in Spanish children.

We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. We enrolled 1200 children. A total of 666 (55.5%) were hospitalised, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalised children, the proportions were 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were age in months (OR: 1.007; 95% CI 1.004 to 1.01), MIS-C (OR: 14.4, 95% CI 8.9 to 23.8), chronic cardiac disease (OR: 4.8, 95% CI 1.8 to 13), asthma or recurrent wheezing (OR: 2.5, 95% CI 1.2 to 5.2) and after excluding MIS-C patients, moderate/severe liver disease (OR: 8.6, 95% CI 1.6 to 47.6). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare.Conclusion: Hospitalised children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease. What is Known: • All studies suggest that children are less susceptible to serious SARS-CoV-2 infection when compared to adults. Most studies describe symptoms at presentation. However, it remains unclear how these symptoms group together into clinically identifiable syndromes and the severity associated with them. What is New: • We have gathered the primary diagnoses into five major syndromes of decreasing severity: MIS-C, bronchopulmonary syndrome, gastrointestinal syndrome, fever without a source and mild syndrome. Classification of the children in one of the syndromes is unique and helps to assess the risk of critical illness and to define the spectrum of the disease instead of just describing symptoms and signs.

Schools as a Framework for COVID-19 Epidemiological Surveillance of Children in Catalonia, Spain: A Population-Based Study.

Objective: We describe and analyze the childhood (<18 years) COVID-19 incidence in Catalonia, Spain, during the first 36 weeks of the 2020-2021 school-year and to compare it with the incidence in adults. Methods: Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests were obtained from the Catalan Agency for Quality and Health Assessment. Overall, 7,203,663 SARS-CoV-2 tests were performed, of which 491,819 were positive (6.8%). We collected epidemiological data including age-group incidence, diagnostic effort, and positivity rate per 100,000 population to analyze the relative results for these epidemiological characteristics. Results: Despite a great diagnostic effort among children, with a difference of 1,154 tests per 100,000 population in relation to adults, the relative incidence of SARS-CoV-2 for <18 years was slightly lower than for the general population, and it increased with the age of the children. Additionally, positivity of SARS-CoV-2 in children (5.7%) was lower than in adults (7.2%), especially outside vacation periods, when children were attending school (4.9%). Conclusions: A great diagnostic effort, including mass screening and systematic whole-group contact tracing when a positive was detected in the class group, was associated with childhood SARS-CoV-2 incidence and lower positivity rate in the 2020-2021 school year. Schools have been a key tool in epidemiological surveillance rather than being drivers of SARS-CoV-2 incidence in Catalonia, Spain.

Household Severe Acute Respiratory Syndrome Coronavirus 2 Transmission and Children: A Network Prospective Study.

BACKGROUND: The role of children in household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. We describe the epidemiological and clinical characteristics of children with coronavirus disease 2019 (COVID-19) in Catalonia, Spain, and investigate the household transmission dynamics. METHODS: A prospective, observational, multicenter study was performed during summer and school periods (1 July 2020-31 October 2020) to analyze epidemiological and clinical features and viral household transmission dynamics in COVID-19 patients aged <16 years. A pediatric index case was established when a child was the first individual infected. Secondary cases were defined when another household member tested positive for SARS-CoV-2 before the child. The secondary attack rate (SAR) was calculated, and logistic regression was used to assess associations between transmission risk factors and SARS-CoV-2 infection. RESULTS: The study included 1040 COVID-19 patients. Almost half (47.2%) were asymptomatic, 10.8% had comorbidities, and 2.6% required hospitalization. No deaths were reported. Viral transmission was common among household members (62.3%). More than 70% (756/1040) of pediatric cases were secondary to an adult, whereas 7.7% (80/1040) were index cases. The SAR was significantly lower in households with COVID-19 pediatric index cases during the school period relative to summer (P = .02) and compared to adults (P = .006). No individual or environmental risk factors associated with the SAR. CONCLUSIONS: Children are unlikely to cause household COVID-19 clusters or be major drivers of the pandemic, even if attending school. Interventions aimed at children are expected to have a small impact on reducing SARS-CoV-2 transmission.

Multi-inflammatory Syndrome in Children Related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Spain.

Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection.