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BackgroundWhen comparing the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe, the associated COVID-19 mortality seems to have decreased substantially. Various factors could explain this trend, including changes in demographic characteristics of infected persons, and the improvement of case management. To date, no study has been performed to investigate the evolution of COVID-19 in-hospital mortality in Switzerland, while also accounting for risk factors. MethodsWe investigated the trends in COVID-19 related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to May 2021, comparing in particular the first and the second wave. We used data from the COVID-19 Hospital-based Surveillance (CH-SUR) database. We performed survival analyses adjusting for well-known risk factors of COVID-19 mortality (age, sex and comorbidities) and accounting for competing risk. ResultsOur analysis included 16,030 episodes recorded in CH-SUR, with 2,320 reported deaths due to COVID-19 (13.0% of included episodes). We found that overall in-hospital mortality was lower during the second wave of COVID-19 compared to the first wave (HR 0.71, 95% CI 0.69 - 0.72, p-value < 0.001), a decrease apparently not explained by changes in demographic characteristics of patients. In contrast, mortality in intermediate and intensive care significantly increased in the second wave compared to the first wave (HR 1.48, 95% CI 1.42 - 1.55, p-value < 0.001), with significant changes in the course of hospitalisation between the first and the second wave. ConclusionWe found that, in Switzerland, COVID-19 mortality decreased among hospitalised persons, whereas it increased among patients admitted to intermediate or intensive care, when comparing the second wave to the first wave. We put our findings in perspective with changes over time in case management, treatment strategy, hospital burden and non-pharmaceutical interventions. Further analyses of the potential effect of virus variants and of vaccination on mortality would be crucial to have a complete overview of COVID-19 mortality trends throughout the different phases of the pandemic.
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ObjectivesTo longitudinally assess severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and clustering of seropositive children within school classes in March-April 2021 compared to June-July and October-November 2020. To examine the evolution of symptoms and the extent of under-detection of SARS-CoV-2 in children. DesignProspective cohort study of randomly selected schools and classes. SettingSchools remained open for physical attendance in Switzerland from May 2020 to the end of 2020/2021 school year. Lower school level (age range 7-10 years) and middle school level (8-13 years) children in primary schools, and upper school level (12-17 years) children in secondary schools were invited for SARS-CoV-2 serological testing in the Ciao Corona study in the canton of Zurich, Switzerland. Three testing rounds were completed in June-July 2020 (T1; after the first wave of SARS-CoV-2 infections), October-November 2020 (T2; during the peak of the second wave), and March-April 2021 (T3; after the second wave and with SARS-CoV-2 variants of concern becoming dominant). Parents completed questionnaires on sociodemographic information and symptoms. Participants2487 children (median age 12 years, age range 7-17 years) recruited from 275 classes in 55 schools participated in the testing in March-April 2021; total of 2974 children participated in at least one of the 3 testing rounds. Main outcome measuresSARS-CoV-2 serology results; clustering of seropositive children within classes; reported symptoms. ResultsThe proportion of children who were SARS-CoV-2 seropositive increased from 1.5% (95% credible interval (CrI) 0.6% to 2.6%) in June-July 2020, to 6.6% (95% CrI 4.0% to 8.9%) in October-November, and to 16.4% (95% CrI 12.1% to 19.5%) in March-April 2021. By March-April 2021, children in upper school level (12.4%; 95% CrI 7.3% to 16.7%) were less likely to be seropositive than those in middle (19.5%; 95% CrI 14.2% to 24.4%) or lower school levels (16.0%; 95% CrI 11.0% to 20.4%). Children in the upper school level had a 5.1% (95% CI -9.4% to -0.7%) lower than expected seroprevalence by March-April 2021 than those in middle school level, based on difference-in-differences analysis. The ratio of PCR-diagnosed to all seropositive children changed from 1 to 21.7 (by June-July 2020) to 1 to 3.5 (by March-April 2021). Symptoms were reported by 37% of newly seropositive and 16% seronegative children. Potential clusters of 3 or more newly seropositive children were detected in 24 of 119 (20%) classes with a high participation rate, from which a median of 17 clusters could be expected due to random distribution of seropositive children within the classes. Clustering was lowest in middle and upper school levels. Retention rate in the cohort was high (84% of T1 participants attended T3). Among participants, supporting society and research were reported more commonly for participation than personal reasons. Fear of blood sampling was the most frequently reported reason for non-participation, reported for 64% of children. ConclusionsBy March-April 2021, 16.4% of children and adolescents were seropositive in the canton of Zurich, Switzerland. The majority of clusters of SARS-CoV-2 seropositive children in school classes could be explained by community rather than intra-class transmission of infections. Seroprevalence and clustering was lowest in upper school levels during all timepoints. Trial registrationClinicalTrials.gov NCT04448717. What is already known on the topicO_LITransmission of SARS-CoV-2 in school setting largely followed community transmission in 2020. C_LIO_LIWith implemented preventive measures, secondary attack rates were low and clustering of SARS-CoV-2 infections within classes and schools (outbreaks) were observed rarely. C_LI What this study addsO_LIWith high community incidence and new variants of SARS-CoV-2, seroprevalence increased in school children between October 2020 - March 2021 in the canton of Zurich in Switzerland, and was higher in lower school levels. C_LIO_LIMost of the potential clusters of children who tested seropositive within classes could be explained by community rather than intra-class transmission of SARS-CoV-2, especially in middle and upper school levels. C_LIO_LIMore children who tested seropositive in March-April 2021 were diagnosed and reported symptoms potentially related to SARS-CoV-2 infection more frequently than those who tested seropositive in June-July or October-November 2020. C_LIO_LIThe most frequent reason for non-participation was fear of blood sampling (62% of children). C_LI
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Determination of SARS-CoV-2 antibody responses in the context of pre-existing immunity to circulating human coronavirus (HCoV) is critical to understanding protective immunity. Here we perform a multifactorial analysis of SARS-CoV-2 and HCoV antibody responses in pre-pandemic (N=825) and SARS-CoV-2-infected donors (N=389) using a custom-designed multiplex ABCORA assay. ABCORA seroprofiling, when combined with computational modeling, enables accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity, and reveals intriguing interrelations with HCoV immunity. Specifically, higher HCoV antibody levels in SARS-CoV-2-negative donors suggest that preexisting HCoV immunity may provide protection against SARS-CoV-2 acquisition. In those infected, higher HCoV activity is associated with elevated SARS-CoV-2 responses, indicating cross-stimulation. Most importantly, HCoV immunity may impact disease severity, as patients with high HCoV reactivity are less likely to require hospitalization. Collectively, this evidence points to HCoV immunity promoting the rapid development of SARS-CoV-2-specific immunity, underscoring the importance of exploring cross-protective responses for comprehensive coronavirus prevention.
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BackgroundSwitzerland had one of the highest incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Europe during the second wave. Schools were open as in most of Europe with specific preventive measures in place. However, the frequency and transmission of acute unrecognized, asymptomatic or oligosymptomatic infections in schools during this time of high community transmission is unknown. Thereof, our aim was to pilot a surveillance system that detects acute SARS-CoV-2 infections in schools and possible transmission within classes. Methods14 out of the randomly selected sample of the Ciao Corona cohort study participated between December 1 and 11, a time when incidence rate for SARS-CoV-2 infections was high for the canton of Zurich. We determined point-prevalence of acute SARS-CoV-2 infections of school children attending primary and secondary school. A buccal swab for polymerase chain reaction (PCR) and a rapid diagnostic test (RDT) to detect SARS-CoV-2 were taken twice 1 week apart (T1 and T2) in a cohort of children from randomly selected classes. A questionnaire assessed demographics and symptoms compatible with a SARS-CoV-2 infection during the past 5 days. ResultsOut of 1299 invited children, 641 (49%) 6- to 16-year-old children and 66 teachers from 14 schools and 67 classes participated in at least 1 of 2 testings. None of the teachers but 1 child had a positive PCR at T1, corresponding to a point-prevalence in children of 0.2% (95% CI 0.0% to 1.1%), and no positive PCR was detected at T2. The child with positive PCR at T1 was negative on the RDT at T1 and both tests were negative at T2. There were 7 (0.6%) false positive RDTs in children and 2 (1.7%) false positive RDTs in teachers at T1 or T2 among 5 schools (overall prevalence 0.7%). All 9 initially positive RDTs were negative in a new buccal sample taken 2 hours to 2 days later, also confirmed by PCR. 35% of children and 8% of teachers reported mild symptoms during the 5 days prior to testing. ConclusionIn a setting of high incidence of SARS-CoV-2 infections, unrecognized virus spread within schools was very low. Schools appear to be safe with the protective measures in place (e.g., clearly symptomatic children have to stay at home, prompt contact tracing with individual and class-level quarantine, and structured infection prevention measures in school). Specificity of the RDT was within the lower boundary of performance and needs further evaluation for its use in schools. Given the low point prevalence even in a setting of very high incidence, a targeted test, track, isolate and quarantine (TTIQ) strategy for symptomatic children and school personnel adapted to school settings is likely more suitable approach than surveillance on entire classes and schools. Trial registrationClinicalTrials.gov NCT04448717 https://clinicaltrials.gov/ct2/show/NCT04448717
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Background and aimsThe facilitating role of schools in SARS-CoV-2 infection spread is still debated and the potential of school closures to mitigate transmission unclear. In autumn 2020, Switzerland experienced one of the highest second waves of the SARS-CoV-2 pandemic in Europe while keeping schools open, thus offering a high-exposure environment to study SARS-CoV-2 infections in schools. The aim of this study was to examine longitudinal change in SARS-CoV-2 seroprevalence in children and the evolution of clustering within classes and schools from June to November, 2020, in a prospective cohort study of school children in the canton of Zurich, Switzerland. MethodsChildren from randomly selected schools and classes, stratified by district, were invited to participate in serological testing of SARS-CoV-2 in June-July and October-November 2020. Parents of children filled questionnaires on sociodemographic and health-related questions. 55 schools and 275 classes within them were enrolled, with 2603 children participating in the first, and 2552 in the second testing (age range 6-16 years). We evaluated longitudinal changes of seroprevalence in districts and investigated clustering of seropositive cases within classes and schools. ResultsOverall SARS-CoV-2 seroprevalence was 2.4% (95% CrI 1.4%-3.6%) in summer and 4.5% (95% CrI 3.2%-6.0%) in not previously seropositive children in late autumn, leading to estimated 7.8% (95% CrI 6.2%-9.5%) of ever seropositive children, without significant differences among lower, middle and upper school levels. Among the 2223 children with serology tested twice, 28 (40%) of previously seropositive were negative, and 109 (5%) previously negative became seropositive. Seroprevalence was not different between school levels or sexes, but varied across districts (1.7% to 15.0%). Between June-July and October-November 2020, the ratio of diagnosed to newly seropositive children was 1 to 8. At least one newly seropositive child was detected in 47 of 55 schools and 90 of 275 classes. Among 130 classes with high participation rate, 0, 1-2 or [≥]3 seropositive children were present in 73 (56%), 50 (38%) and 7 (5%) classes, respectively. Class level explained slightly more variation of individual serological results (standard deviation of random effects (SD) 0.97) than school level (SD 0.61) in the multilevel logistic regression models. Symptoms were reported for 22% of seronegative and 29% of newly seropositive children since summer. ConclusionsUnder a regimen of open schools with some preventive measures in place since August, clustering of seropositive cases occurred in very few classes and not across entire schools despite a clear increase in seropositive children during a period of high transmission of SARS-CoV-2. Trial registrationClinicalTrials.gov NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717
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BackgroundSARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world causing several million victims in 213 countries. Switzerland was severely hit by the virus, with 43000 confirmed cases as of September 1st, 2020. AimIn cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19 in addition to their mandatory reporting system. MethodsPatients hospitalised for more than 24 hours with a positive PCR test, from 20 Swiss hospitals, are included. Data collection follows a custom Case Report Form based on WHO recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms started more than 5 days after the patients admission date. ResultsAs of September 1st, 2020, 3645 patients were included. Most patients were male (2168 - 59.5%),and aged between 50 and 89 years (2778 - 76.2%), with a median age of 68 (IQR 54-79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported: hypertension (1481 - 61.7%), cardiovascular diseases (948 - 39.5%), and diabetes (660 - 27.5%) being the most frequent in adults; respiratory diseases and asthma (4 -21.1%), haematological and oncological diseases (3 - 15.8%) being the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly for respiratory diseases (2470 - 93.2% in adults, 16 - 55.2% in children), renal (681 - 25.7%) and cardiac (631 - 23.8%) complication for adults. The second and third most frequent complications in children affected the digestive system and the liver (7 - 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989 - 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. 527 (14.5%) deaths were registered, all among adults. ConclusionThe surveillance system has been successfully initiated and provides a very representative set of data for Switzerland. We therefore consider it to be a valuable addition to the existing mandatory reporting, providing more precise information on the epidemiology, risk factors, and clinical course of these cases.
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BackgroundRT-PCR of nasopharyngeal swabs (NPS) is the acknowledged gold standard for the detection of SARS-CoV-2 infection. Rising demands for repetitive screens and mass-testing necessitate, however, the development of additional test strategies. Saliva may serve as an alternative to NPS as its collection is simple, non-invasive and amenable for mass- and home-testing but rigorous validation of saliva particularly in children is missing. MethodsWe conducted a large-scale head-to-head comparison of SARS-CoV-2 detection by RT-PCR in saliva and nasopharyngeal swab (NPS) of 1270 adults and children reporting to outpatient test centers and an emergency unit for an initial SARS-CoV-2 screen. The saliva collection strategy developed utilizes common, low-cost plastic tubes, does not create biohazard waste at collection and was tailored for self-collection and suitability for children. ResultsIn total, 273 individuals were tested SARS-CoV-2 positive in either NPS or saliva. SARS-CoV-2 RT-PCR results in the two specimens showed a high agreement (Overall Percent Agreement = 97.8%). Despite lower viral loads in saliva of both adults and children, detection of SARS-CoV-2 in saliva compared well to NPS (Positive Percent Agreement = 92.5%). Importantly, in children, SARS-CoV-2 infections were more often detected in saliva than NPS (Positive Predictive Value = 84.8%), underlining that NPS sampling in children can be challenging. ConclusionsThe comprehensive parallel analysis reported here establishes saliva as a generally reliable specimen for the detection of SARS-CoV-2 with particular advantages for testing children that is readily applicable to increase and facilitate repetitive and mass-testing in adults and children. Article Summary Main PointsComparison with nasopharyngeal swabs in a large test center-based study confirms that saliva is a reliable and convenient material for the detection of SARS-CoV-2 by RT-PCR in adults and increases detection efficacy in children.
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Importance: Understanding transmission and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in school children is critical to implement appropriate mitigation measures. Objective: To determine the variation in SARS-CoV-2 seroprevalence in school children across districts, schools, grades, and classes, and the relationship of SARS-CoV-2 seroprevalence with self-reported symptoms. Design: Cross-sectional analysis of baseline measurements of a longitudinal cohort study (Ciao Corona) from June-July 2020. Setting: 55 randomly selected schools and classes stratified by district in the canton of Zurich, Switzerland (1.5 million inhabitants). Participants: Children, aged 6-16 years old, attending grades 1-2, 4-5 and 7-8. Exposure: Exposure to circulating SARS-CoV-2 between February and June 2020 including public lock-down and school closure (March 16-May 10, 2020). Main Outcomes and Measures: Variation in seroprevalence of SARS-CoV-2 in children across 12 cantonal districts, schools, and grades using a Luminex-based antibody test with four targets for each of IgG, IgA and IgM. Clustering of cases within classes. Analysis of associations of seropositivity and symptoms. Comparison of seroprevalence with a randomly selected adult population, based on Luminex-based IgG and IgA antibody test of Corona Immunitas. Results: In total, 55 schools and 2585 children were recruited (1337 girls, median age 11, age range 6-16 years). Overall seroprevalence was 2.8 % (95% CI 1.6-4.1%), ranging from 1.0% to 4.5% across districts. Seroprevalence was 3.8% (1.9-6.1%) in grades 1-2, 2.5% (1.1-4.2%) in grades 4-5, and 1.5% (0.5-3.0%) in grades 7-8. At least one case was present in 36/55 tested schools and in 43/128 classes with [≥]50% participation rate and [≥]5 children tested. 73% of children reported COVID-19 compatible symptoms since January 2020, but none were reported more frequently in seropositive compared to seronegative children. Seroprevalence of children was very similar to seroprevalence of randomly selected adults in the same region in June-July 2020, measured with the same Corona Immunitas test, combining IgG and IgA (3.1%, 95% CI 1.4-5.4%, versus 3.3%, 95% CI 1.4-5.5%). Conclusions and Relevance: Seroprevalence was inversely related to age and revealed a dark figure of around 90 when compared to 0.03% confirmed PCR+ cases in children in the same area by end of June. We did not find clustering of SARS-CoV-2 seropositive cases in schools so far, but the follow-up of this school-based study will shed more light on transmission within and outside schools. Trial registration: ClinicalTrials.gov Identifier: NCT04448717, registered June 26, 2020. https://clinicaltrials.gov/ct2/show/NCT04448717
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IntroductionSeroprevalence and transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents, especially in school setting, are not clear. Resulting uncertainty is reflected in very different decisions on school closures and reopenings across countries. The aim of this longitudinal cohort study is to assess the extent and patterns of seroprevalence of SARS-CoV-2 antibodies in school-attending children repeatedly. It will examine risk factors for infection, relationship between seropositivity and symptoms, and temporal persistence of antibodies. Additionally, it will include testing of school personnel and parents. Methods and analysisThe study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children aged 5 to 16 years, attending classes in primary and secondary schools are invited. Venous blood and saliva samples are collected for SARS-CoV-2 serological testing after the first wave of infections (June/July 2020), in fall (October/November 2020), and after winter (March/April 2021). Venous blood is also collected for serological testing of parents and school personnel. Bi-monthly questionnaires to children, parents and school personnel cover SARS-CoV-2 symptoms and tests, health, preventive behavior, lifestyle and quality of life information. Total seroprevalence and cumulative incidence will be calculated. Hierarchical Bayesian logistic regression models will account for sensitivity and specificity of the serological test in the analyses and for the complex sampling structure, i.e., clustering within classes and schools. Ethics and disseminationThe study was approved by the Ethics Committee of the Canton of Zurich, Switzerland (2020-01336). The results of this study will be published in peer-reviewed journals and will be made available to study participants and participating schools, the Federal Office of Public Health, and the Educational Department of the canton of Zurich. Trial registration number NCT04448717. O_LICiao Corona is a large, prospective school-based cohort study and will provide robust data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence, transmission routes and immunity over time in a representative sample of school children. C_LIO_LIThe longitudinal design will allow describing temporal trends of immunity to SARS-CoV-2 infection and to evaluate effects of school structure and preventive measures. C_LIO_LIThis study will inform goal-oriented policy decisions in school management during subsequent outbreaks. C_LIO_LIParticipation bias, missing questionnaires, desirability bias, and loss of follow up may occur. The validity of serological tests may also hamper results. C_LI