Epidemiology of 7375 children and adolescents hospitalized with COVID-19 in Germany, reported via a prospective, nationwide surveillance study in 2020-2022.

By means of a nationwide, prospective, multicenter, observational cohort registry collecting data on 7375 patients with laboratory-confirmed SARS-CoV-2 admitted to children's hospitals in Germany, March 2020-November 2022, our study assessed the clinical features of children and adolescents hospitalized due to SARS-CoV-2, evaluated which of these patients might be at highest risk for severe COVID-19, and identified underlying risk factors. Outcomes tracked included: symptomatic infection, case fatality, sequelae at discharge and severe disease. Among reported cases, median age was one year, with 42% being infants. Half were admitted for reasons other than SARS-CoV-2. In 27%, preexisting comorbidities were present, most frequently obesity, neurological/neuromuscular disorders, premature birth, and respiratory, cardiovascular or gastrointestinal diseases. 3.0% of cases were admitted to ICU, but ICU admission rates varied as different SARS-CoV-2 variants gained prevalence. Main risk factors linked to ICU admission due to COVID-19 were: patient age (> 12 and 1-4 years old), obesity, neurological/neuromuscular diseases, Trisomy 21 or other genetic syndromes, and coinfections at time of hospitalization. With Omicron, the group at highest risk shifted to 1-4-year-olds. For both health care providers and the general public, understanding risk factors for severe disease is critical to informing decisions about risk-reduction measures, including vaccination and masking guidelines.

High burden of acute respiratory tract infections leading to hospitalization at German pediatric hospitals: fall/winter 2022-2023.

PURPOSE: Given reduced immunity levels for seasonally occurring respiratory infections and the experience of an unusually early, severe wave of RSV infections during 2021, a preexisting clinician-led reporting system (CLRS) was updated to prospectively monitor the anticipated high burden of respiratory infections (ARI) in German pediatric hospitals during fall/winter 2022-2023. METHODS: From September 13, 2022 through March 31, 2023, children hospitalized with ARI as a primary diagnosis were monitored via a national CLRS established by the German Society for Pediatric Infectious Diseases (DGPI). Once a week, the CLRS collected overall number of new hospital admissions, ARI-related admissions according to pathogen (SARS-CoV-2, RSV, influenza, and other), plus number of patients admitted to ICU with ARI as a primary diagnosis. RESULTS: With a high participation among children's hospitals across Germany (22.8%), 76 centers submitted 1,053 survey reports. ARI-related hospital admissions showed a steep rise starting in late September 2022 and reached their highpoint in early December 2022 (50.1% of all admissions). In parallel, the average number of newly admitted patients (aNA) with RSV (3.6) peaked, as did those with influenza (2.1) one week later. The average highpoint of ARI patients on ICU (aICU) (2.9) was reached shortly thereafter. Again, RSV (1.6) und influenza (1.2) were predominant pathogens. CONCLUSION: In fall/winter 2022-2023, German hospitals reported a sharp increase in patients with ARIs. While RSV and influenza represented the greatest proportion of ARI, SARS-CoV-2 played a less significant role. Systematic, dynamic collection of ARI data is critical for assessing real burdens on the health care system.

FamilyCoviDD19: results of a cross-sectional study-long-term outcomes of infected and uninfected household members.

OBJECTIVE: In this study, we aimed to compare long-term physical and mental health outcome between SARS-CoV-2 infected and uninfected household members to differentiate between infection-related and pandemic-related outcomes after about two and a half years of the pandemic. Furthermore, possible differences in the outcome of adults and children and young people (CYP) were of interest. DESIGN: In a cross-sectional study design, we compared the long-term physical and mental health outcome of between infected and uninfected as well as between adult and CYP (household members). SETTING: The FamilyCoviDD19 study-a serology study in households-was initially conducted to evaluate virus transmission in a close contact setting focusing on households with children and adolescents in Germany. At least 1 year after initial infection in the respective households, a follow-up took place in which the prevalence and type of possible long-term consequences were surveyed on the basis of self-reported information on physical and mental health. PARTICIPANT: In this study, a total of 533 household members of 146 families participated and responded to our survey, including 296 (55.5%) adults and 237 (44.5%) CYP. RESULT: The difference in frequency of reported symptoms between infected and uninfected individuals was very moderate, suggesting that the vast majority of reported symptoms were not attributable to a previous SARS-CoV-2 infection. However, regardless of age and infection status, this study showed overall high rates of self-reported symptoms with CYP having fewer long-term sequelae than adults one year after infection. Furthermore, over 50% of those reporting symptoms were not affected in their daily life, with CYPs reporting an even lower percentage compared with adults. CONCLUSION: CYP are at reduced risk not only to develop symptomatic infection or severe disease courses (previous analyses) but also to develop infection-associated long-term sequelae (this study). Independent of infection CYP reported high rates of neurocognitive, pain, somatic and mood symptoms, which makes the influence of the pandemic itself-including pandemic control measures-decisive.

Preserved perception-action integration in adolescents after a COVID-19 infection.

Evidence is accumulating that the Coronavirus disease (COVID-19) can bring forth deficits in executive functioning via alterations in the dopaminergic system. Importantly, dopaminergic pathways have been shown to modulate how actions and perceptions are integrated within the brain. Such alterations in event file binding could thus underlie the cognitive deficits developing after a COVID-19 infection. We examined action-perception integration in a group of young people (11-19 years of age) that had been infected with COVID-19 before study participation (n = 34) and compared them to a group of uninfected healthy controls (n = 29) on the behavioral (i.e., task accuracy, reaction time) and neurophysiological (EEG) level using an established event file binding paradigm. Groups did not differ from each other regarding demographic variables or in reporting psychiatric symptoms. Overall, multiple lines of evidence (behavioral and neurophysiological) suggest that action-perception integration is preserved in adolescents who suffered from COVID-19 prior to study participation. Event file binding processes were intact in both groups on all levels. While cognitive impairments can occur following a COVID-19 infection, the study demonstrates that action-perception integration as one of the basic building blocks of cognition seems to be largely unaffected in adolescents with a rather mild course of the disease.

Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection.

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children. This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time. Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19.

Comparing SARS-CoV-2 variants among children and adolescents in Germany: relative risk of COVID-19-related hospitalization, ICU admission and mortality.

PURPOSE: SARS-CoV-2 infections cause COVID-19 and have a wide spectrum of morbidity. Severe disease courses among children are rare. To date, data on the variability of morbidity in relation to variant of concern (VOC) in children has been sparse and inconclusive. We compare the clinical severity of SARS-CoV-2 infection among children and adolescents in Germany during the Wildtype and Alpha combined, Delta and Omicron phases of the COVID-19 pandemic. METHODS: Comparing risk of COVID-19-related hospitalization, intensive care unit (ICU) admission and death due to COVID-19 in children and adolescents, we used: (1) a multi-center seroprevalence study (SARS-CoV-2-KIDS study); (2) a nationwide registry of pediatric patients hospitalized with SARS-CoV-2 infections; and (3) compulsory national reporting for RT-PCR-confirmed SARS-CoV-2 infections in Germany. RESULTS: During the Delta predominant phase, risk of COVID-19-related hospitalization among all SARS-CoV-2 seropositive children was 3.35, ICU admission 1.19 and fatality 0.09 per 10,000; hence about halved for hospitalization and ICU admission and unchanged for deaths as compared to the Wildtype- and Alpha-dominant period. The relative risk for COVID-19-related hospitalization and ICU admission compared to the alpha period decreased during Delta [0.60 (95% CI 0.54; 0.67) and 0.51 (95% CI 0.42; 0.61)] and Omicron [0.27 (95% CI 0.24; 0.30) and 0.06 (95% CI 0.05; 0.08)] period except for the < 5-year-olds. The rate of case fatalities decreased slightly during Delta, and substantially during Omicron phase. CONCLUSION: Morbidity caused by SARS-CoV-2 infections among children and adolescents in Germany decreased over the course of the COVID-19 pandemic, as different VOCs) emerged.

A comparison of pediatric inflammatory multisystem syndrome temporarily-associated with SARS-CoV-2 and Kawasaki disease.

The connection between Pediatric Inflammatory Multisystem Syndrome (PIMS) and Kawasaki Disease (KD) is not yet fully understood. Using the same national registry, clinical features and outcome of children hospitalized in Germany, and Innsbruck (Austria) were compared. Reported to the registry were 395 PIMS and 69 KD hospitalized patients. Patient age in PIMS cases was higher than in KD cases (median 7 [IQR 4-11] vs. 3 [IQR 1-4] years). A majority of both PIMS and KD patients were male and without comorbidities. PIMS patients more frequently presented with organ dysfunction, with the gastrointestinal (80%), cardiovascular (74%), and respiratory (52%) systems being most commonly affected. By contrast, KD patients more often displayed dermatological (99% vs. 68%) and mucosal changes (94% vs. 64%), plus cervical lymph node swelling (51% vs. 34%). Intensive care admission (48% vs. 19%), pulmonary support (32% vs. 10%), and use of inotropes/vasodilators (28% vs. 3%) were higher among PIMS cases. No patients died. Upon patient discharge, potentially irreversible sequelae-mainly cardiovascular-were reported (7% PIMS vs. 12% KD). Despite differences in age distribution and disease severity, PIMS and KD cases shared many common clinical and prognostic characteristics. This supports the hypothesis that the two entities represent a syndrome continuum.

Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany.

BACKGROUND: Long-term health sequelae of the Coronavirus Disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post-COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults. METHODS AND FINDINGS: We used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR: 2.28, 95% CI: 1.71 to 3.06, p < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR: 1.30, 95% CI: 1.25 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, IR COVID-19: 615.82, IR Control: 464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias. CONCLUSIONS: In this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults. TRIAL REGISTRATION: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.

Associations of early childhood medication exposure and molar incisor hypomineralization (MIH): A routine data analysis.

OBJECTIVES: Molar incisor hypomineralization (MIH) has become a major oral health problem of widely unknown origin. Besides genetic predisposition, exposure to certain drugs in early childhood are suspected to be associated with MIH. Aim of this routine data analysis was to examine associations of MIH and exposure to medication as well as perinatal factors. METHODS: Individuals with MIH were identified in claims data using a validated predefined specific treatment pattern. The database was a comprehensive routine data set of a major national health insurance company (BARMER, Germany). Based on this treatment pattern a MIH group and an unaffected control group were formed for analysis. Various medical data including medical diagnoses and prescriptions were available. Associations were examined comparing results for a set of variables in both groups. Differences between the groups were tested for significance using T-tests (P<0.01). RESULTS: Between 2010 to 2019, a total of 298,502 children between 6 and 9 years of age were included in this analysis. 22,947 were assigned to the MIH group. For individuals in this group, significantly larger prescription quantities in the main ATC (Anatomical, Therapeutic, Chemical) groups J (antiinfectives for systemic use), R (respiratory system) and S (sensory organs) were found in the first 4 years of life compared to MIH unaffected individuals. With antibiotics, there were both significantly larger prescription quantities and significantly higher numbers of respective prescriptions in the first 4 years of life. The differences amounted up to about 10.62% in frequently used antibiotics to be found in ATC J01D (other beta-lactam antibacterials) for the number of prescriptions in the 4th year of life. No association was found for premature birth, mode of delivery or the use of antipyretic or anti-inflammatory medication. CONCLUSIONS: While perinatal factors do not seem to be associated with MIH development, early life exposure to antibiotics might play a role. CLINICAL SIGNIFICANCE STATEMENT: Although causal relations can still not be proven, a responsible use of the unquestionably beneficial antibiotics is encouraged from a clinical point of view.

Burden of Pediatric SARS-CoV-2 Hospitalizations during the Omicron Wave in Germany.

(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents were not yet available. Given Omicron's high transmissibility, the ability to assess its impact on admission and hospitalization rates in children's hospitals is critical for the purpose of understanding the scope of its burden on the German healthcare system. (2) Methods: From 24 January 2022 to 31 July 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and the need for respiratory support, were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4-3) per reporting pediatric hospital per day was hospitalized in general wards, whereas a median of 0.1 cases (range 0-0.4 cases) was admitted to intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with the need for intensive care treatment and respiratory support due to symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children's hospitals.

Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany.

Importance: During the COVID-19 pandemic, a reduction in quality of life and physical and mental health among children and adolescents has been reported that may be associated with SARS-CoV-2 infection and/or containment measures. Objective: To assess the association of SARS-CoV-2 seropositivity with symptoms that may be related to myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS) among children and adolescents. Design, Setting, and Participants: This substudy of the cross-sectional SARS-CoV-2 seroprevalence surveys in Germany (SARS-CoV-2 KIDS) was performed in 9 pediatric hospitals from May 1 to October 31, 2021. Pediatric patients were recruited during an inpatient or outpatient visit regardless of the purpose of the visit. Parental questionnaires and serum samples were collected during clinically indicated blood draws. The parental questionnaire on demographic and clinical information was extended by items according to the DePaul Symptom Questionnaire, a pediatric screening tool for ME/CFS in epidemiological studies in patients aged 5 to 17 years. Exposures: Seropositivity was determined by SARS-CoV-2 IgG antibodies in serum samples using enzyme-linked immunosorbent assays. Main Outcomes and Measures: Key symptoms of ME/CFS were evaluated separately or as clustered ME/CFS symptoms according to the DePaul Symptom Questionnaire, including fatigue. Results: Among 634 participants (294 male [46.4%] and 340 female [53.6%]; median age, 11.5 [IQR, 8-14] years), 198 (31.2%) reported clustered ME/CFS symptoms, including 40 of 100 SARS-CoV-2-seropositive (40.0%) and 158 of 534 SARS-CoV-2-seronegative (29.6%) children and adolescents. After adjustment for sex, age group, and preexisting disease, the risk ratio for reporting clustered ME/CFS symptoms decreased from 1.35 (95% CI, 1.03-1.78) to 1.18 (95% CI, 0.90-1.53) and for substantial fatigue from 2.45 (95% CI, 1.24-4.84) to 2.08 (95% CI, 1.05-4.13). Confinement to children and adolescents with unknown previous SARS-CoV-2 infection status (n = 610) yielded lower adjusted risks for all symptoms except joint pain ME/CFS-related symptoms. The adjusted risk ratio was 1.08 (95% CI, 0.80-1.46) for reporting clustered ME/CFS symptoms and 1.43 (95% CI, 0.63-3.23) for fatigue. Conclusions and Relevance: These findings suggest that the risk of ME/CFS in children and adolescents owing to SARS-CoV-2 infection may be very small. Recall bias may contribute to risk estimates of long COVID-19 symptoms in children. Extensive lockdowns must be considered as an alternative explanation for complex unspecific symptoms during the COVID-19 pandemic.

Risk for severe outcomes of COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany.

Although children and adolescents have a lower burden of SARS-CoV-2-associated disease compared to adults, assessing the risk for severe outcomes among SARS-CoV-2-infected children remains difficult due to a high rate of undetected cases. We combine data from three data sources - a national seroprevalence study (the SARS-CoV-2 KIDS study), the nationwide, state-based reporting system for PCR-confirmed SARS-CoV-2 infections in Germany, and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or pediatric inflammatory multisystem syndrome (PIMS-TS, also known as MIS-C) - in order to provide estimates on the risk of hospitalization for COVID-19-related treatment, intensive care admission, and death due to COVID-19 and PIMS-TS in children. The rate of hospitalization for COVID-19-related treatment among all SARS-CoV-2 seropositive children was 7.13 per 10,000, ICU admission 2.21 per 10,000, and case fatality was 0.09 per 10,000. In children without comorbidities, the corresponding rates for severe or fatal disease courses were substantially lower. The lowest risk for the need of COVID-19-specific treatment was observed in children aged 5-11 without comorbidities. In this group, the ICU admission rate was 0.37 per 10,000, and case fatality could not be calculated due to the absence of cases. The overall PIMS-TS rate was 2.47 per 10,000 SARS-CoV-2 infections, the majority being children without comorbidities. CONCLUSION: Overall, the SARS-CoV-2-associated burden of a severe disease course or death in children and adolescents is low. This seems particularly the case for 5-11-year-old children without comorbidities. By contrast, PIMS-TS plays a major role in the overall disease burden among all pediatric age groups. WHAT IS KNOWN: • SARS-CoV-2-associated burden of disease in children is considered to be low, but accurate risk estimates accounting for clinically undiagnosed infections are lacking. • Asymptomatic SARS-CoV-2 infections are common in children. WHAT IS NEW: • We provide risk estimates for hospitalization for COVID-19-related treatment, ICU admission, death from COVID-19, and PIMS-TS for children with SARS-CoV-2 infections by pooling different data sources. • The risk for PIMS-TS exceeds the risk for severe COVID-19 in all age groups; the risk for severe COVID-19 is the lowest in 5-11 years old.

Restrictive prescription of antibiotics in preterm infants with premature rupture of membranes.

BACKGROUND: In preterm infants with premature rupture of membranes, antibiotic treatment is frequently started but rates of early onset sepsis are lower. In line with national guidelines, a stratified approach in the decision to start antibiotic treatment using maternal history, clinical impression and biomarkers has been implemented in our level III neonatal center and its results are evaluated. METHODS: Retrospective cohort study of all preterm newborns with rupture of membranes at least 1 h prior to delivery admitted to our tertiary neonatal intensive care unit. Data on antibiotic exposure, mortality and major neonatal complications were extracted from the electronic patient charts to evaluate the effects and safety of our stratified approach. RESULTS: Four hundred fifty-six infants met the inclusion criteria. 120 (26%) received primary antibiotics whereas 336 (74%) did not. Of those receiving primary antibiotics, 13 (11%) had a blood culture positive sepsis, 46 (38%) met the criteria of clinical sepsis and in 61 (51%) sepsis was ruled out and antibiotics were stopped after 48-96 h. All infants with blood culture positive sepsis were identified and treated within the first 24 h of life using this approach. None of the 336 infants who were not started on antibiotics primarily needed antibiotic therapy within the first 5 days of life. There were no deaths or major neonatal complications in the group that did not receive empiric antibiotics. CONCLUSIONS: Our stratified approach for preterm infants with premature rupture of membranes allows a safe reduction of antibiotic exposure even in this high risk population. As a result, only 25% of high risk preterm newborns are treated with antibiotics of which more than half receive less than 5 days of treatment. To treat one infant with blood culture positive sepsis, only 9 infants receive empiric antibiotics.

High burden of RSV hospitalizations in Germany 2021-2022.

BACKGROUND: Public health measures implemented to mitigate the effects of the COVID-19 pandemic disrupted the worldwide transmission of endemic respiratory viruses such as RSV, as well as other typical, seasonal, and viral respiratory pathogens. METHODS: From October 18, 2021 to March 31, 2022, RSV cases admitted to German pediatric hospitals were monitored via a newly established, national, Clinician-Led Reporting System (CLRS) that recorded patient age and type of respiratory support. A subanalysis of the first 4 months of the monitoring period was additionally performed. RESULTS: In October 2021, a total of 471 hospitalized pediatric RSV cases per day were documented by 67 reporting hospitals. By January 2022, this number dropped to three cases at 11 hospitals (median of reporting hospitals: 37 (11%)). During these months, the median of hospitalized children on general wards and intensive care units was 133 and 15, respectively. In the subanalysis conducted to examine the period October to January, an average of 3.6 ± 2.2 patients per hospital per day were hospitalized on general wards (median 4 cases; range 0.3-8 cases), whereas 0.4 ± 2.2 patients were on intensive care units (median 0.3 cases; range 0-0.9 cases), with 11.5% receiving respiratory support. The majority of patients were under 2 years old. CONCLUSION: The overall burden of out-of-season RSV cases was extraordinarily high in Germany in 2021-2022. The newly established CLRS may help evaluate and, therefore, better allocate local and national pediatric care resources.

Seroprevalence of SARS-CoV-2 in German secondary schools from October 2020 to July 2021: a longitudinal study.

PURPOSE: To quantify the number of SARS-CoV-2 infections in students and teachers in 14 Secondary schools in eastern Saxony, Germany. Seroprevalence of SARS-CoV-2 antibodies in study population. Number of undetected cases. METHODS: Serial seroprevalence study. RESULTS: The role of educational settings in the SARS-CoV-2 Pandemic is still controversial. Seroprevalence increases from 0.8 to 5.9% from October to December when schools remained open and to 12.2% in March/April during a strict lockdown with closed schools. The ratio of undetected to detected cases decreased from 0.76 to 0.44 during the study period. CONCLUSION: During the second and third wave of the pandemic in Germany, students and teachers are not overrepresented in SARS-CoV-2 infections. The percentage of undetected cases is moderate and decreases over time. The risk of contracting SARS-CoV-2 within the household is higher than contracting it in educational settings making school closures rather ineffective in terms of pandemic control measures or individual risk reduction in children and adolescents. TRIAL REGISTRATION: DRKS00022455 (July 23rd, 2020).

Comparison of mental health outcomes in seropositive and seronegative adolescents during the COVID19 pandemic.

Post-COVID19 complications such as pediatric inflammatory multisystem syndrome (PIMS) and Long-COVID19 move increasingly into focus, potentially causing more harm in young adolescents than the acute infection. To better understand the symptoms of long-term mental health outcomes in adolescents and distinguish infection-associated symptoms from pandemic-associated symptoms, we conducted a 12 question Long-COVID19 survey. Using this survey, we compared the responses on neurocognitive, general pain and mood symptoms from seropositive and seronegative adolescents in a cross-sectional study design. Since May 2020, students grade 8-12 in fourteen secondary schools in Eastern Saxony were enrolled in the SchoolCovid19 study. Serostatus was assessed regularly in all participants. In March/April 2021, 1560 students with a median age of 15 years participated at the regular study visit after re-opening of the schools in mid-March and responded to our Long-COVID19 survey as part of this visit. 1365 (88%) students were seronegative, 188 (12%) were seropositive. Each symptom asked in the Long-COVID19 survey was present in at least 35% of the students within the last seven days before the survey. With the exception of seropositive students being less sad, there was no significant difference comparing the reported symptoms between seropositive students and seronegative students. The lack of differences comparing the reported symptoms between seropositive and seronegative students suggests that Long-COVID19 might be less common than previously thought and emphasizes on the impact of pandemic-associated symptoms regarding the well-being and mental health of young adolescents.Clinical Trial Registration: SchoolCoviDD19: Prospektive Erfassung der SARS-CoV-2 Seropositivität bei Schulkindern nach Ende der unterrichtsfreien Zeit aufgrund der Corona-Schutz-Verordnung (COVID-19), DRKS00022455, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022455.

Prevalence and Transmission of Severe Acute Respiratory Syndrome Coronavirus Type 2 in Childcare Facilities: A Longitudinal Study.

OBJECTIVE: To evaluate the role of childcare facilities in the transmission of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in a longitudinal study to gain further knowledge of SARS-CoV-2 prevalence, transmission, and spread among preschool children, their parents, and their caregivers. STUDY DESIGN: Children aged 1-6 years, their parents, and their caregivers in 14 childcare facilities in Dresden, Saxony/Germany were invited to participate in the KiTaCoviDD19-study between July 2020 and January 2021. Seroprevalence of SARS-CoV-2 antibodies was assessed up to 4 times during the study period in all participating adults, and demographic characteristics, as well as epidemiologic information on personal SARS-CoV-2 history were obtained. Samples for stool virus shedding of SARS-CoV-2 were analyzed by polymerase chain reaction every 2-4 weeks in all participating children. RESULTS: In total, 318 children, 299 parents and 233 childcare workers were enrolled. By January 2021, 11% of the participating adults were found to be seropositive, whereas the percentage of children shedding SARS-CoV-2 was 6.8%. Overall, we detected 17 children with SARS-CoV-2 virus shedding in 8 different childcare facilities. In 4 facilities, there were a maximum of 3 connected cases in children. Approximately 50% of SARS-CoV-2 infections in the children could not be connected to a secondary case in our study population. CONCLUSIONS: This study does not provide evidence of relevant asymptomatic ("silent") spread of SARS-CoV-2 in childcare facilities in both low- and high-prevalence settings. Our findings add to the evidence that childcare and educational settings do not have a crucial role in driving the SARS-CoV-2 pandemic.

Kinetics and seroprevalence of SARS-CoV-2 antibodies: a comparison of 3 different assays.

Comparing seroprevalence and antibody kinetics in three different commercially available assays for SARS-CoV-2. Serostatus of COVID-19 patients was analyzed 5 months and 10 months after their infection, using three different assays: Diasorin LIAISON, Euroimmun, Abbott Diagnostics ARCHITECT. Seropositivity at baseline differed significantly depending on the assay (Diasorin 81%, Euroimmun 83%, Abbott 59%). At follow-up antibody levels detected in the Diasorin assay were stable, while there was a significant loss in seropositivity in the Euroimmun and Abbott assays. There are significant differences in SARS-CoV-2 antibody kinetics based on the specific assay used.

Clinical manifestations and outcome of SARS-CoV-2 infections in children and adolescents with rheumatic musculoskeletal diseases: data from the National Paediatric Rheumatology Database in Germany.

OBJECTIVES: This study aimed to investigate the clinical manifestations, course and outcome of SARS-CoV-2 infection among children and adolescents with rheumatic and musculoskeletal diseases (RMD). Due to their underlying disease as well due to therapeutic immunosuppression, these patients may be at risk for a severe course of COVID-19 or for a flare of the underlying disease triggered by SARS-CoV-2 infection. METHODS: Demographic, clinical and treatment data from juvenile patients with RMD as well as data about SARS-CoV-2 infection like test date and method, clinical characteristics, disease course, outcome and impact on the disease activity of the RMD were documented on a specific SARS-CoV-2 questionnaire implemented in the National Paediatric Rheumatology Database (NPRD) in Germany. The survey data were analysed descriptively. RESULTS: From 17 April 2020 to 16 February 2021, data were collected from 76 patients (52% female) with RMD and laboratory-proven SARS-CoV-2 infection with median age of 14 years, diagnosed with juvenile idiopathic arthritis (58%), autoinflammatory (24%) and connective tissue disease (8%). Fifty-eight patients (76%) received disease-modifying antirheumatic drugs (DMARDs), 41% biological DMARDs and 11% systemic glucocorticoids. Fifty-eight (76%) had symptoms of COVID-19. Disease course of SARS-CoV-2 infection (classified as asymptomatic, mild, moderate, severe, life-threatening) was mild and outcome of COVID-19 (classified as recovered, not yet recovered, permanent damage or deceased) was good (recovered) in the majority of patients. Two patients were hospitalised, one of whom required intensive care and died of cardiorespiratory failure. In 84% of SARS-CoV-2-positive patients, no relevant increase in disease activity of the RMD was observed. CONCLUSIONS: In our cohort, SARS-CoV-2 infection in juvenile patients with RMD under various medications was mild with good outcome in the majority of cases and does not appear to have a relevant impact on disease activity of the underlying condition.