Clinical and Laboratory Biomarkers as Predictors of Severity in Pediatric Inflammatory Multisystem Syndrome-temporally Associated With SARS-CoV-2: Data From a Prospective Nationwide Surveillance Study in Switzerland.

BACKGROUND: PIMS-TS (pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2) is a rare but serious condition in children following SARS-CoV-2 infection, characterized by a range of clinical symptoms with varying severity. Understanding risk factors for severe PIMS-TS is crucial for appropriate and timely intervention. OBJECTIVE: To identify factors associated with increased PIMS-TS severity in children. METHODS: In this nationwide prospective observational study, epidemiological and clinical data was collected from children <18 years of age with suspected or confirmed PIMS-TS from all 29 pediatric hospitals in Switzerland. Children were categorized into 3 groups according to admission to intensive care unit (ICU): non-ICU, ICU-moderate and ICU-severe, defined as requirement of invasive ventilation and/or inotropic support. RESULTS: A total of 204 children were included; 99 (49%) were categorized as non-ICU, 50 (25%) as ICU-moderate and 55 (27%) as ICU-severe. In ICU-severe cases, respiratory and neurological symptoms were more frequent compared with non-ICU cases: 72% versus 47%, P < 0.001 and 66% versus 41%, P = 0.001, respectively. Compared with the non-ICU group, children in the ICU-severe group had lower lymphocyte counts, higher neutrophil-lymphocyte ratios, lower platelet counts, as well as higher C-reactive protein, N-terminal pro-B-type natriuretic peptide, troponin T and creatinine levels at admission. Lymphopenia and elevated troponin T levels at admission were associated with an increased risk of being in the ICU-severe group. CONCLUSION: The severity of PIMS-TS may be predicted using clinical symptoms and laboratory biomarkers, which help clinicians in decision-making and management of patients.

The changing clinical presentation of COVID-19 in children during the course of the pandemic.

AIM: To investigate the evolution of clinical symptoms of COVID-19 in children throughout the pandemic. METHODS: In this national prospective surveillance study, symptoms in children hospitalised with COVID-19 were collected from all paediatric hospitals in Switzerland between March 2020 and March 2023. Data was analysed across four time periods, according to the predominantly circulating SARS-CoV-2 variant: T1 (wild-type), T2 (Alpha), T3 (Delta) and T4 (Omicron), as well as by age group. RESULTS: The study included 1323 children. The proportion of children admitted to an intensive care unit remained stable throughout the pandemic. However, the pattern and frequency of clinical manifestations changed over time. Respiratory symptoms were less prevalent during T1 (wild-type), fever during T2 (Alpha) and rash during T4 (Omicron). In contrast, fever and neurological symptoms were more prevalent during T4 (Omicron). Newly described symptoms during T4 (Omicron) included conjunctivitis, laryngotracheitis and seizures. Fever was more prevalent among neonates and infants whereas respiratory symptoms were more common among infants. Gastrointestinal symptoms were more frequent among toddlers, while both toddlers and school-aged children presented with neurological symptoms more often than other age groups. CONCLUSION: Continuous surveillance is required to detect changes in manifestations and there by be prepared for the optimal management of complications in children with COVID-19.

SARS-CoV-2 seroconversion in children attending daycare versus adults in Germany between October 2020 and June 2021.

BACKGROUND: Data on seroconversion rates after SARS-CoV-2 infection in young children (<6 years) is scarce. The present study compares seroconversion rates between young children and adults and identifies associated factors. METHODS: The COALA study ("Corona-outbreak-related examinations in daycare centers") investigated transmission dynamics of SARS-CoV-2 in daycare centers and associated households (10/2020-06/2021). 114 individuals tested positive for SARS-CoV-2 through PCR either prior to the study period by health authorities or in PCR testing during the study period. Two capillary blood samples were obtained within five weeks consecutively and tested for SARS-CoV-2 IgG-antibodies (second sampling depending on positive PCR). Results from 91 participants (38 young children 1-6 years, 53 adults) were included in the analyses. RESULTS: Seroconversion rate in young children is significantly higher than in adults (97.4% versus 66%). High viral load and longer time interval between the probable date of infection and antibody testing are associated with seroconversion. CONCLUSIONS: Our findings depict substantial development of specific antibodies in young children after SARS-CoV-2 infection. This may provide temporary protection from re-infection for young children or severe disease for this age group.

When fighting an infectious disease, the immune system often produces antibodies. These proteins circulate in the blood, where they help to clear the infection and generally remain present for several months after recovery. Little is known about how often children younger than 6 years develop antibodies after SARS-CoV-2 infection. The aim of our study was to compare antibody development of young children and adults. We examined blood samples from young children and adults after SARS-CoV-2 outbreaks in daycare centers during the early pandemic (10/2020­06/2021) in Germany. Young children and adults who tested positive for SARS-CoV-2 had two blood samples taken at an interval of five weeks. We found that young children are more likely to develop antibodies after SARS-CoV-2 infection than adults. These findings indicate that young children may be­at least temporarily­protected from re-infection or from a severe course of the disease.

Physical activity promotion in daycare centres in Germany: study protocol for a cross-sectional survey within the BeweKi study.

INTRODUCTION: In Germany, a total of 92.2% of children between the age of 3 and school entry age attend daycare centres. Therefore, daycare centres are a suitable setting to promote physical activity among children. Yet, there is a lack of knowledge on the promotion of physical activity in daycare centres with regards to different structures and concepts, culture/policies/practices and the characteristics of directors and pedagogical staff of daycare centres in Germany. The aim of this study is to investigate (a) the status quo, as well as (b) the fostering and hindering conditions (barriers and facilitators) of physical activity promotion in daycare centres in Germany. METHODS AND ANALYSIS: The cross-sectional study will collect data from November 2022 to February 2023. For the sample, about 5500 daycare centres will be drawn from an address database available through the German Youth Institute (DJI) and invited to the survey. From each daycare centre a director and a pedagogical staff member will be asked to fill in a standardised self-administered questionnaire. The survey explores characteristics of the daycare centre and the implementation of physical activity promotion, for example, the extent and form of physical activity promotion, the use and size of indoor and outdoor area, structural conditions such as personal and financial resources, personal attitudes towards physical activity promotion, demographic characteristics of pedagogical staff, structural daycare centre's characteristics such as proportion of children from socioeconomic disadvantaged groups. In addition, micro-geographical data on socioeconomic and infrastructural environment of the daycare centres will be included in the data set. ETHICS AND DISSEMINATION: The study has been received and approved by the Commissioner for Data Protection of the Robert Koch Institute and by the Ethics Committee of Alice Salomon Hochschule Berlin, University of Applied Sciences. Results will be disseminated through publications and presentations to scientific community and stakeholders.

SARS-CoV-2 viral clearance and viral load kinetics in young children (1-6 years) compared to adults: Results of a longitudinal study in Germany.

Objective: To investigate SARS-COV-2 viral clearance and viral load kinetics in the course of infection in children aged 1-6 years in comparison with adults. Methods: Prospective cohort study of infected daycare children and staff and their close contacts in households from 11/2020 to 06/2021. Adult participants took upper respiratory tract specimen from themselves and/or their children, for PCR tests on SARS-CoV-2. Data on symptoms and exposure were used to determine the date of probable infection for each participant. We determined (a) viral clearance, and (b) viral load dynamics over time. Samples were taken from day 4-6 to day 16-18 after diagnosis of the index case in the respective daycare group (5 samples per participant). Results: We included 40 children (1-6 years) and 67 adults (18-77 years) with SARS-CoV-2 infection. Samples were available at a mean of 4.3 points of time per participant. Among the participants, the 12-day study period fell in different periods within the individual course of infection, ranging from day 5-17 to day 15-26 after assumed infection.Children reached viral clearance at a median of 20 days after assumed infection (95% CI 17-21 days, Kaplan-Meier Analysis), adults at 23 days (95% CI 20-25 days, difference not significant). In both children and adults, viral load decreased over time with trajectories of the mean viral load not being statistically different between groups. Kaplan-Meier calculations show that from day 15 (95% CI 13-15), 50% of all participants had a viral load <1 million copies/ml, i.e. were no longer infectious or negative. Conclusion: Children aged 1-6 and adults infected with SARS-CoV-2 (wild type and Alpha variant) did not differ significantly in terms of viral load kinetics and time needed to clear the virus. Therefore, containment measures are important also in the daycare settings as long as the pandemic continues.

[Symptoms of SARS-CoV-2 infections in children of day care age]. / Symptomatik einer akuten SARS-CoV-2-Infektion bei Kindern im Kita-Alter.

Background: The symptoms of SARS-CoV­2 infections in children are mostly mild; however, the symptoms are highly variable. There are only a few studies on non-hospitalized children. The clinical picture described in hospitalized children cannot be transferred to non-hospitalized children and the frequency of certain symptoms in children may thus be overestimated. Furthermore, most studies include a broad age group (up to 18 years). The symptoms of younger children have so far been described in less detail. Objective: The paper aims to describe the frequency of COVID-19 symptoms in younger children (1-6 years old). Data of the two modules COALA (Corona: Anlassbezogene Untersuchungen in Kitas) and CATS (Corona-KiTa surveillance) of the Corona-KiTa study are evaluated and the results of the two studies are compared and discussed against the background of the different methodologies. In the COALA study, the type and frequency of symptoms of children infected with SARS-CoV­2 are evaluated and compared to symptoms of children who tested negative for SARS-CoV­2. Symptom frequencies of SARS-CoV­2 infected children of the COALA study are compared with data collected from surveillance data (CATS). Material and methods: The COALA study investigated 30 SARS-CoV­2 outbreaks in day care centers where at least 1 SARS-CoV­2 case was reported between October 2020 and June 2021. Using a prospective study design, day care children who were infected with SARS-CoV­2 and their contact persons were studied over a period of 12 days (including regular SARS-CoV­2 testing, retrospective interviews and daily symptom reporting). The results from the COALA study were compared with data from COVID-19 surveillance cases (CATS) for the same age group and time period. In Germany, SARS-CoV­2 cases are reported to the local health authorities by physicians and laboratories. When reporting cases symptoms can be reported as well. Results: From the COALA study, interview and reported symptom data were available for 289 children from the participating day care centers. Of 39 children with a SARS-CoV­2 infection (wild-type, α­variant), 64% had at least 1 symptom; of the children who tested negative for SARS-CoV­2, 40% had at least 1 symptom. In both groups, rhinitis was the most common symptom (36% vs. 25%, n. s.). From the surveillance data (CATS), clinical information was available for 84,371 SARS-CoV­2 positive children; fever was most common (27%) along with rhinitis (26%). Severe symptoms such as dyspnea were rarely reported in the outbreak investigations and in the surveillance data (3% and 1%, respectively). Conclusion: Day care-aged children infected with SARS-CoV­2 usually have mild or asymptomatic courses. Their symptoms are similar to those of children who tested negative for SARS-CoV­2 from the same day care centers; thus, the observed COVID-19 symptoms are nonspecific. Combining data from the two modules is useful: findings from a very large database, as provided by the surveillance data, are complemented by findings from day care center outbreaks, where detailed prospective data on infected children can be compared with those of children who tested negative for SARS-CoV­2.

Transmission of SARS-CoV-2 among children and staff in German daycare centres.

In daycare centres, the close contact of children with other children and employees favours the transmission of infections. The majority of children <6 years attend daycare programmes in Germany, but the role of daycare centres in the SARS-CoV-2 pandemic is unclear. We investigated the transmission risk in daycare centres and the spread of SARS-CoV-2 to associated households. 30 daycare groups with at least one recent laboratory-confirmed SARS-CoV-2 case were enrolled in the study (10/2020-06/2021). Close contact persons within daycare and households were examined over a 12-day period (repeated SARS-CoV-2 PCR tests, genetic sequencing of viruses, symptom diary). Households were interviewed to gain comprehensive information on each outbreak. We determined primary cases for all daycare groups. The number of secondary cases varied considerably between daycare groups. The pooled secondary attack rate (SAR) across all 30 daycare centres was 9.6%. The SAR tended to be higher when the Alpha variant was detected (15.9% vs. 5.1% with evidence of wild type). The household SAR was 53.3%. Exposed daycare children were less likely to get infected with SARS-CoV-2 than employees (7.7% vs. 15.5%). Containment measures in daycare programmes are critical to reduce SARS-CoV-2 transmission, especially to avoid spread to associated households.