Comparison of Pediatric Inflammatory Multisystem Syndrome temporarily-associated with SARS-CoV-2 and Kawasaki Disease: Results from a nationwide German registry 2020-2021 (preprint)

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.

SARS-CoV-2 variants and the risk of Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 in children in Germany (preprint)

Purpose: To investigate the risk of Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children depending on periods with different dominant variants of concern (VOC) of SARS-CoV-2.Methods: The risk of developing PIMS-TS in three phases of the pandemic with different VOC (Alpha, Delta, and Omicron) was calculated using data of rtPCR confirmed SARS-CoV-2 infections extracted from the German statutory notification system and reports of cases with PIMS-TS captured by a national, prospective registry. Overall and age group-specific rate ratios of PIMS-TS rates in the different observation periods, using the Alpha period as the baseline, were calculated.Results: The rate of PIMS-TS changed significantly over time. During April-August 2021, with dominant VOC Alpha_B.1.1.7, the PIMS-TS rate was 6.19 (95% confidence intervals (95% CI) 5.17, 7.20), decreased to 1.68 (95% CI 1.49, 1.87) in August 2021 to January 2022 with Delta_AY and to 0.89 (95% CI 0.79, 1.00) in January-April 2022 with Omicron_BA as dominant VOC. This corresponds to a decrease in PIMS-TS rate of 73% (rate ratio 0.271, 95% CI 0.222; 0.332) and 86% (rate ratio 0.048, 95% CI 0.037; 0.062), respectively, compared to the Alpha period. Rate ratios were almost identical for all age groups.Conclusion: The data strongly suggest a relation of the risk for PIMS-TS to the prevailing VOC with the highest risk related to Alpha_B.1.1.7 and the lowest with Omicron_BA. Uniformity of the decrease across age groups does not suggest a major role for vaccination on the risk of PIMS-TS in infected children.

Risk of Hospitalization, severe disease, and mortality due to COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany (preprint)

Background: Although children and adolescents have a lower burden of SARS-CoV-2-associated disease as compared to adults, assessing absolute risk among children remains difficult due to a high rate of undetected cases. However, without more accurate case numbers, reliable risk analyses are impossible. Methods: We combine data from three sources - a national seroprevalence study (the SARS-CoV-2 KIDS study), the German statutory notification system and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or Pediatric Inflammatory Multisystem Syndrome (PIMS-TS) - in order to provide reliable estimates on childrens hospitalization, intensive care admission and death due to COVID-19 and PIMS-TS. Results: While the overall hospitalization rate associated with SARS-CoV-2 infection was 35.9 per 10,000 children, ICU admission rate was 1.7 per 10,000 and case fatality was 0.09 per 10,000. Children without comorbidities were found to be significantly less likely to suffer from a severe or fatal disease course. The lowest risk was observed in children aged 5-11 without comorbidities. In this group, the ICU admission rate was 0.2 per 10,000 and case fatality could not be calculated, due to an absence of cases. The overall PIMS-TS rate was 1 per 4,000 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 overall disease burden among all pediatric age groups.

SARS-CoV-2 Antibodies in Children: A One-Year Seroprevalence Study From June 2020 to May 2021 in Germany (preprint)

Background: Investigating the role of children in the COVID-19 pandemic is pivotal to prevent the virus spreading. In most cases, children infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) develop non-specific symptoms or are asymptomatic. Therefore, the infection rate among this age group remains unclear. Seroprevalence studies, including clinical questionnaires, may contribute to our understanding of the time course and clinical manifestations of SARS-CoV-2 infections.Methods: SARS-CoV-2-KIDS is a longitudinal, hospital-based, multicentre study in Germany on the seroprevalence of anti-SARS-CoV-2 immunoglobulin G, as determined by an Enzyme-Linked Immunosorbent Assay in children (aged ≤17 years). A study-specific questionnaire provided additional information on clinical aspects.Findings: This analysis included 10,358 participants recruited from June 2020 to May 2021. The estimated anti-SARS-CoV-2 seroprevalence increased from 2·0% (95% confidence interval (95% CI) 1·6, 2·5) to 10·8% (95% CI 8·7, 12·9) in March 2021, without major change afterwards and was higher in children with migrant background (on average 6·6% vs. 2·8%). In the pandemic early stages, children under three years were 3·5 (95% CI 2·2, 5·6) times more likely to be seropositive than older children, with the levels equalising in later observations. History of self-reported respiratory tract infections or pneumonia was associated with seropositivity (OR 1·8 (95% CI 1·4, 2·3); 2·7 (95% CI 1·7, 4·1)).Interpretation: The majority of children in Germany do not have detectable SARS-CoV-2 IgG. To some extent, this may reflect the effect of differing containment measures implemented in the federal states. Detection levels might have been greater in certain age groups or migrant background. Lifting containment measurements is likely to cause a general increase in respiratory tract infections, which already pose a challenge to paediatric medical care during regular winter seasons. This challenge might become critical with additional infections caused by SARS-CoV-2.Funding: Funding Information: German Federal Ministry of Education and Research.Declaration of Interests: Authors have no conflicts of interest to declare.Ethics Approval Statement: Ethics committees of each study centre independently approved the study protocol. All parents/guardians gave written informed consent and children assented to the participation when appropriate for their age.

Risk factors for hospitalization, disease severity and mortality in children and adolescents with COVID-19: Results from a nationwide German registry (preprint)

Objective To characterize the clinical features of children and adolescents hospitalized with SARS-CoV-2 infections and to explore predictors for disease severity. Design Nationwide prospective observational cohort study. Setting Data collected from 169 out of 351 childrens hospitals in Germany between March 18, 2020 and April 30, 2021 and comparison with the Statutory Notification System. Participants 1,501 children and adolescents up to 19 years of age with laboratory confirmed SARS-CoV-2 infections who were admitted to childrens hospitals and subsequently reported to the COVID-19 registry of the German Pediatric Infectious Disease Society (DGPI). Main outcome measures Admission to intensive care, in-hospital. Results As compared to the information in the statutory notification system, up to 30% of all children and adolescents hospitalized in Germany during the study period were reported to the DGPI registry. Median age was three years (IQR, 0-12), with 36% of reported cases being infants. Although roughly half of patients in the registry were not admitted to the hospital due to their SARS-CoV-2 infection, 72% showed infection-related symptoms during hospitalization. Preexisting comorbidities were present in 28%, most commonly respiratory disorders, followed by neurological, neuromuscular, and cardiovascular diseases. Median length of hospitalization was five days (IQR 3-10). Only 20% of patients received a SARS-CoV-2-related therapy. Infants were less likely to require therapy as compared to older children. Overall, 111 children and adolescents were admitted to intensive care units (ICU). In a fully adjusted model, patient age, trisomy 21, coinfections and primary immunodeficiencies (PID) were significantly associated with intensive care treatment. In a bivariate analysis, pulmonary hypertension, cyanotic heart disease, status post (s/p) cardiac surgery, fatty liver disease, epilepsy and neuromuscular impairment were statistically significant risk factors for ICU admission. Conclusion Overall, a small proportion of children and adolescents was hospitalized in Germany during the first year of the pandemic. The majority of patients within our registry was not admitted due to COVID-19 suggesting an overestimation of the disease burden even in hospitalized children. Nevertheless, a large proportion of children and adolescents with confirmed COVID-19 reported in Germany could be captured. This allowed for detailed assessment of overall disease severity and underlying risk factors in our cohort. The main risk factors for COVID-19 disease associated intensive care treatment were older patient age, trisomy 21, PIDs and coinfection at the time of hospitalization. Trial registration Registry of hospitalized pediatric patients with SARS-CoV-2 infection (COVID-19), DRKS00021506