Long/post-COVID in children and adolescents: symptom onset and recovery after one year based on healthcare records in Germany.

PURPOSE: Evidence on the incidence and persistence of post-acute sequelae of COVID-19 (PASC) among children and adolescents is still limited. METHODS: In this retrospective cohort study, 59,339 children and adolescents with laboratory-confirmed COVID-19 in 2020 and 170,940 matched controls were followed until 2021-09-30 using German routine healthcare data. Incidence rate differences (ΔIR) and ratios (IRR) of 96 potential PASC were estimated using Poisson regression. Analyses were stratified according to age (0-11, 12-17 years), and sex. At the individual level, persistence of diagnoses in patients with onset symptoms was tracked starting from the first quarter post-infection. RESULTS: At 0-3 month follow-up, children and adolescents with a previous SARS-CoV-2 infection showed a 34% increased risk of adverse health outcome, and approximately 6% suffered from PASC in association with COVID-19. The attributable risk was higher among adolescents (≥ 12 years) than among children. For most common symptoms, IRRs largely persisted at 9-12 month follow-up. IRR were highest for rare conditions strongly associated with COVID-19, particularly inflammatory conditions among children 0-11 years, and chronic fatigue and respiratory insufficiency among adolescents. Tracking of diagnoses at the individual level revealed similar rates in the decline of symptoms among COVID-19 and control cohorts, generally leaving less than 10% of the patients with persistent diagnoses after 12 months. CONCLUSION: Although very few patients presented symptoms for longer than 12 months, excess morbidity among children and, particularly, adolescents with a history of COVID-19 means a relevant burden for pediatric care.

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.

Recognition and management of children and adolescents with conduct disorder: a real-world data study from four western countries.

BACKGROUND: Conduct disorders (CD) are among the most frequent psychiatric disorders in children and adolescents, with an estimated worldwide prevalence in the community of 2-4%. Evidence-based psychological outpatient treatment leads to significant improvement in about two-thirds of cases. However, there seems to be considerable variation in rates of CD diagnoses and implementation of evidence-based interventions between nations. The aim of this study was to compare administrative prevalence and treatment patterns for CD in children and adolescents seen in health care systems across four Western countries (Denmark, Germany, Norway, and the USA). METHODS: Cross-sectional observational study using healthcare data to identify children and adolescents (aged 0-19 years) with an ICD-10 code for CD within the calendar year 2018. Within each country's study population, the prevalence of CD, psychiatric comorbidity, psychopharmacological treatment, and psychiatric hospitalisation was calculated. RESULTS: The prevalence of diagnosed CD differed 31-fold between countries: 0.1% (Denmark), 0.3% (Norway), 1.1% (USA) and 3.1% (Germany), with a male/female ratio of 2.0-2.5:1. The rate of psychiatric comorbidity ranged from 69.7 to 86.1%, with attention-deficit/hyperactivity disorder being most common. Between 4.0% (Germany) and 12.2% (USA) of youths with a CD diagnosis were prescribed antipsychotic medication, and 1.2% (Norway) to 12.5% (Germany) underwent psychiatric hospitalisation. CONCLUSION: Recognition and characteristics of youths diagnosed with CD varied greatly by country. In some countries, the administrative prevalence of diagnosed CD was markedly lower than the average estimated worldwide prevalence. This variation might reflect country-specific differences in CD prevalence, referral thresholds for mental health care, diagnostic tradition, and international variation in service organisation, CD recognition, and availability of treatment offers for youths with CD. The rather high rates of antipsychotic prescription and hospitalisation in some countries are remarkable, due to the lack of evidence for these therapeutic approaches. These findings stress the need of prioritising evidence-based treatment options in CD. Future research should focus on possible reasons for inter-country variation in recognition and management of CD, and also address possible differences in patient-level outcomes.

Economic burden of respiratory syncytial virus in adults in Germany - a health claims analysis between 2015 and 2018.

AIMS: Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections (LRTI) in infants and adults. While the clinical burden was recently estimated in adults in Germany, little is known about the economic burden. To fill this gap, this study aimed to assess hospital and outpatient healthcare resource utilization (HRU) and costs of RSV infections in adults in Germany. METHODS: In this retrospective, observational study on nationwide, representative, anonymized claims data (2015-2018), we identified patients ≥18 years with ICD-10-GM-codes specific to RSV ("RSV-specific"). To increase sensitivity, patients with unspecified LRTIs (including unspecified bronchitis, bronchiolitis, bronchopneumonia, and pneumonia) during RSV seasons were also included as cases potentially caused by RSV ("RSV-possible"). RSV-related HRU (hospital days, ICU and ventilation treatment, drug dispensation) and direct costs were estimated per episode. Excess costs per episode and for follow-up periods were compared to a matched control cohort. All outcomes were reported per healthcare sector and stratified by age and risk groups as well as disease severity (ICU admission/ventilation). RESULTS: Direct inpatient and outpatient mean episode costs were 3,473€ and 82€, respectively, with substantially higher costs for severe cases requiring intensive care and/or ventilation (10,801€). Direct costs for RSV-specific cases were higher than for RSV-possible cases (inpatients: 6,247€ vs. 3,450€; outpatients: 127€ vs. 82€). Moreover, costs were significantly higher for RSV patients than for controls and increased over time (inpatients: 5,140€ per episode vs 10,093€ per year; outpatients: 46€ per quarter vs 114€ per year). LIMITATIONS: While the number of RSV-specific cases was low, inclusion of seasonal LRTI cases likely increased the sensitivity to detect RSV cases and allowed a better estimation of the total costs of RSV. CONCLUSIONS: The economic burden of RSV-LRTI in adults in Germany is substantial, persists long-term, and is particularly high in the elderly. This highlights the need for cost-effective prevention measures.

Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study.

OBJECTIVES: To investigate whether the risk of developing an incident autoimmune disease is increased in patients with prior COVID-19 disease compared to those without COVID-19, a large cohort study was conducted. METHOD: A cohort was selected from German routine health care data. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19. RESULTS: In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune diseases of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune disease. CONCLUSIONS: SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection. Key Points • In the 3 to 15 months after acute infection, patients who had suffered from COVID-19 had a 43% (95% CI: 37-48%) higher likelihood of developing a first-onset autoimmune disease, meaning an absolute increase in incidence of 4.50 per 1000 person-years over the control group. • COVID-19 showed the strongest association with vascular autoimmune diseases.