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Background: Post-viral symptoms have long been known in the medical community but have received more public attention during the COVID-19 pandemic. Many post-viral symptoms were reported as particularly frequent after SARS-CoV-2 infection. However, there is still a lack of evidence regarding the specificity, frequency and persistence of these symptoms in comparison to other viral infectious diseases such as influenza., Methods: We investigated a large population-based cohort based on German routine healthcare data. We matched 573,791 individuals with a PCR-test confirmed SARS-CoV-2 infection from the year 2020 to contemporary controls without SARS-CoV-2 infection and controls from the last influenza outbreak in 2018 and followed them up to 18 months., Results: We found that post-viral symptoms as defined for COVID-19 by the WHO as well as tissue damage were more frequent among the COVID-19 cohort than the influenza or contemporary control cohort. The persistence of post-viral symptoms was similar between COVID-19 and influenza., Conclusion: Post-viral symptoms following SARS-CoV-2 infection constitute a substantial disease burden as they are frequent and often persist for many months. As COVID-19 is becoming endemic, the disease must not be trivialized. Research should focus on the development of effective treatments for post-viral symptoms., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Hypothalamic obesity (HO) is defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment-related damage to the hypothalamus. HO epidemiology is poorly understood. We developed a database algorithm supporting the standardized identification of tumor/treatment-related HO (TTR-HO) patients. The algorithm is used to estimate incidence rates of TTR-HO patients in the German healthcare context from a representative claims database (n = 5.42 million) covering 2010-2020. Patients were identified based on surgery/radiotherapy procedures and HO-associated tumor diagnoses (n = 3976). HO was defined by incident obesity and validated based on incident diabetes insipidus diagnoses and desmopressin prescription within a 12-month period after surgery/radiotherapy. Uncertainty due to algorithm definitions is explored in sensitivity analyses. Estimated annual incidence of TTR-HO in Germany is between 0.7 and 1.7 cases per 1,000,000 persons (2019 prevalence: n = 1262 patients). With observed cases in all age groups, two HO-incidence peaks are identified: children/young adults aged 10-24 years and adults aged 40-44 years. Most frequent HO-validated tumor diagnoses are benign sellar/suprasellar tumors (6.1/1,000,000 persons over 9 years), including tumors of the craniopharyngeal duct (1.3/1,000,000), neoplasms of the pituitary gland (4.1/1,000,000), and nonspecific brain tumors of endocrine glands (2.4/1,000,000). This is the first real-world database analysis of TTR-HO epidemiology, refining current estimates of HO epidemiology and early patient identification. A more comprehensive characterization of patients with HO as well as a better understanding of clinical implications will be crucial in developing optimal treatment strategies to improve patient outcomes., (© 2024 The Author(s). Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Introduction: Invasive meningococcal disease (IMD) causes significant mortality and long-term sequelae. This study assesses the potential public health impact of adolescent vaccination strategies employing MenACWY and MenC vaccines in Germany, where the existing meningococcal immunisation programme predominantly involves MenC administration in toddlers., Methods: A dynamic transmission model was developed to simulate the carriage of five meningococcal serogroup compartments (AY/B/C/W/Other) from 2019 until 2060 within 1-year age groups from 0 to 99 years of age. IMD cases were estimated based on case-carrier ratios. The model considered vaccine effectiveness against carriage acquisition and IMD., Results: The model predicts that introducing MenACWY adolescent vaccination could lead to a considerable reduction in IMD incidence, with the potential to prevent up to 65 cases per year and a cumulative total of 1467 cases by 2060. This decrease, mainly driven by herd effects, would result in a reduction of IMD incidence across all age groups, regardless of vaccination age. Furthermore, implementing MenACWY vaccination in adolescents is projected to decrease annual MenACWY-related IMD mortality by up to 64%, equating to an overall prevention of 156 IMD deaths by 2060. These protective outcomes are expected to culminate in approximately 2250 life years gained (LYG) throughout the model's projected time horizon. In contrast, the adoption of MenC vaccination in adolescents is predicted to have minimal influence on both IMD incidence and mortality, as well as on LYG., Conclusion: The results of this study demonstrate that implementing MenACWY vaccination for adolescents in Germany is likely to notably reduce IMD incidence and mortality across age groups. However, the introduction of MenC adolescent vaccination shows only limited impact. Considering the extensive healthcare resources typically required for IMD management, these findings suggest the potential for economic benefits associated with the adoption of MenACWY adolescent vaccination, warranting further cost-effectiveness analysis., (© 2024. The Author(s).)

Introduction: Pertussis is a highly contagious respiratory infection. It affects people of all ages, yet evidence of the impact of pertussis in adults with underlying conditions (UCs) is scarce. This study investigated the incidence and complication rate of pertussis in adult patients with and without UC., Methods: A retrospective analysis was conducted using routinely collected German claims data between 2015 and 2019. Patients with and without different pneumological, cardiovascular, endocrinological, musculoskeletal, and psychological UCs were matched for incidence estimation. Logistic regression models were used to estimate the risk of pertussis depending on the presence of UCs. Negative binomial models were used to assess complication rates in patients with pertussis and with and without UC., Results: In total, 4383 patients were diagnosed with pertussis during the study period. Patients with any UC had an increased risk for pertussis compared to matched patients without UC (odds ratio [OR] 1.72; 95% confidence interval [CI]1.60-1.84, p < 0.0001). Underlying asthma had the highest risk of pertussis (OR 2.70; 95% CI 2.50-2.91, p < 0.0001), followed by chronic obstructive pulmonary disease (OR 2.35; 95% CI 2.10-2.60, p < 0.0001) and depression (OR 2.08; 95% CI 1.95-2.22, p < 0.0001). Severe complications occurred in 10.8% of the pertussis cohort (13.4% with UC vs. 9.5% without UC). The UC-attributable effect on the risk of severe pertussis-related complications was significantly increased for any UC (incidence rate ratio [IRR] 1.29, 95% CI 1.19-1.39). The severe complication risk was also increased for patients aged 60+ (IRR 1.59, 95% CI 1.46-1.72)., Conclusion: This study shows that adults with certain UCs have an increased risk for pertussis and are more likely to have complications. These results provide further evidence that pertussis is a relevant and impactful infectious disease in adults with and without certain UC, indicating that these patients need to be considered when developing vaccination recommendations to avoid pertussis and its associated complications. A graphical abstract is available with this article., (© 2024. The Author(s).)

Background: In 2003, the WHO aimed for a 75% or higher influenza vaccination rate among at-risk populations. However, this target was achieved in a few groups during selected seasons in some European countries, and never in Germany. Adults with underlying conditions (UCs) are a critical negleted group for influenza vaccination. This study aimed to identify data gaps in influenza burden and vaccination coverage among adults under 60 with UCs in Germany and bridge these gaps using real-world data., Material and Methods: We conducted systematic research and analyses using German administrative and claims databases from June 2016 to April 2024. We report on epidemiology, direct care costs, indirect costs from work incapacity, vaccination coverage rates, and describe data gaps., Results: Influenza data for high-risk populations are limited. Comprehensive data on influenza epidemiology and vaccination coverage rates (VCR) is available, though with a delay in data availability. Before and after the pandemic, individuals aged 50-59 had the highest rates of influenza-related hospitalization and ICU admission compared to younger age groups. Across all age groups and seasons, individuals with UC experienced higher rates of medically attended influenza cases, hospitalizations, and healthcare costs, with those aged 35-59 being particularly vulnerable. Vaccine coverage was higher in adults aged 35-59 compared to those aged 18-24, and in females compared to males., Limitations: Discrepancies of vaccination status, limited data availability, and variations among the extent of UCs., Conclusion: In Germany, recent policy measures have mainly targeted those aged 60 and above. While this elderly population experiences the highest disease-related impact, influenza can also lead to substantial healthcare resource utilization (HCRU) and costs in younger populations with chronic UCs; Facilitating vaccination access for this group, such as through pharmacies, is essential. Definition of quantifiable vaccination targets and measures to increase vaccination rates based on these targets are required.

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., (© 2023. International League of Associations for Rheumatology (ILAR).)

Aim: We aimed to develop a risk score to calculate a person's individual risk for a severe COVID-19 course (POINTED score) to support prioritization of especially vulnerable patients for a (booster) vaccination., Subject and Methods: This cohort study was based on German claims data and included 623,363 individuals with a COVID-19 diagnosis in 2020. The outcome was COVID-19 related treatment in an intensive care unit, mechanical ventilation, or death after a COVID-19 infection. Data were split into a training and a test sample. Poisson regression models with robust standard errors including 35 predefined risk factors were calculated. Coefficients were rescaled with a min-max normalization to derive numeric score values between 0 and 20 for each risk factor. The scores' discriminatory ability was evaluated by calculating the area under the curve (AUC)., Results: Besides age, down syndrome and hematologic cancer with therapy, immunosuppressive therapy, and other neurological conditions were the risk factors with the highest risk for a severe COVID-19 course. The AUC of the POINTED score was 0.889, indicating very good predictive validity., Conclusion: The POINTED score is a valid tool to calculate a person's risk for a severe COVID-19 course., Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01884-7., Competing Interests: Conflict of interestFT, JJ, JS, JW, MR, MS, and ON report institutional funding for parts of this project from the German BMBF. Unrelated to this study, JS reports grants for investigator-initiated research from the German GBA, the BMG, BMBF, EU, Federal State of Saxony, Novartis, Sanofi, ALK, and Pfizer. He also participated in advisory board meetings for Sanofi, Lilly, and ALK. MB reports payment for data analysis which is presented in this paper from DAK-Gesundheit. Unrelated to this study, MB reports grants from German GBA, Pfizer, and Sanofi Pasteur and consulting fees from Janssen-Cilag. He participated in an advisory board for GSK. SB is Head of Analytics and Data Science at AOK PLUS, Dresden, Germany. The other authors declare that they have no competing interest., (© The Author(s) 2023.)

Background: The significant annual burden caused by seasonal influenza has led to global calls for increased influenza vaccination coverage rates (VCRs). We aimed to estimate the proportion of the German population at high risk of serious illness from influenza due to chronic conditions and to estimate age-specific VCRs of people with/without chronic conditions., Methods: Using health insurance claims data covering nine influenza seasons (2010-2019), we assessed up to 7 million insured individuals per season across all German regions. Individuals were classified according to age and presence of chronic health conditions. VCRs were estimated using outpatient healthcare utilization documentation., Results: In the 2018-2019 influenza season, 47.3% of individuals had ≥1 chronic condition. Most common were circulatory disorders, accounting for more than a third of individuals with ≥1 condition. Prevalence of chronic diseases, and therefore the proportion of high-risk individuals, increased slightly over time across most age groups. A downward trend in influenza VCRs was observed in all age groups until the 2017-2018 season, followed by a noticeable increase in the 2018-2019 season. Highest VCRs occurred among individuals of ≥60 years, with a 38.5% VCR for this age group in the 2018-2019 season. Several factors, including age, chronic condition type, and geographical location, affected VCRs., Conclusions: Influenza VCRs in individuals at high risk of severe complications from influenza infection are insufficient. Our results suggest that intensified public health efforts are necessary to reach the World Health Organization vaccination coverage target of 75%., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AV, FE, FT, JJ, JS, JW, MR, MS, and ON report institutional funding for parts of this project from the German BMBF. Unrelated to this study, FT reports payments for lectures from Dresden International University. JA reports grants from the Federal State of Saxony. Unrelated to this study, JS reports grants for investigator-initiated research from the German GBA, the BMG, BMBF, EU, Federal State of Saxony, Novartis, Sanofi, ALK, and Pfizer. He also participated in advisory board meetings for Sanofi, Lilly, and ALK. MB reports payment for data analysis which is presented in this paper from DAK‐Gesundheit. Unrelated to this study, MB reports grants from German GBA and Sanofi Pasteur and consulting fees from Janssen‐Cilag. He participated in an advisory board for GSK. NT is member of the Steering Committee of the German Society for Pediatric Infectious Diseases (DGPI) and is the DGPI-mandated person for the pediatric expert group on long-COVID in children and adolescents. SB is Head of Analytics and Data Science at AOK PLUS, Dresden, Germany. Unrelated to this study, STSCH reports payments for a guest lecture at TU Berlin. The other authors declare that they have no competing interest., (Copyright: © 2022 Roessler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In December 2019, the Digital Health Care Act ("Digitale-Versorgung-Gesetz") introduced a general entitlement to the provision and reimbursement of digital health applications (DiGA) for insured persons in the German statutory health insurance. As establishing a new digital service area within the solidarity-based insurance system implies several administrative and regulatory challenges, this paper aims to describe the legal framework for DiGA market access and pricing as well as the status quo of the DiGA market. Furthermore, we provide a basic approach to deriving value-based DiGA prices.To become eligible for reimbursement, the Federal Institute for Drugs and Medical Devices evaluates the compliance of a DiGA with general requirements (e.g., safety and data protection) and its positive healthcare effects (i.e., medical benefit or improvements of care structure and processes) in a fast-track process. Manufacturers may provide evidence for the benefits of their DiGA either directly with the application for the fast-track process or generate it during a trial phase that includes temporary reimbursement. After one year of \]reimbursement, the freely-set manufacturer price is replaced by a price negotiated between the National Association of Statutory Health Insurance Funds and the manufacturer. By February 2022, 30 DiGA had successfully completed the fast-track process. 73% make use of the trial phase and have not yet proven their benefit. Given this dynamic growth of the DiGA market and the low minimum evidence standards, fair pricing remains the central point of contention. The regulatory framework makes the patient-relevant benefits of a DiGA a pricing criterion to be considered in particular. Yet, it does not indicate how the benefits of a DiGA should be translated into a reasonable price. Our evidence-based approach to value-based DiGA pricing approximates the SHI's willingness to pay by the average cost-effectiveness of one or more established therapy in a field of indication and furthermore considers the positive healthcare effects of a DiGA.The proposed approach can be fitted into DiGA pricing processes under the given regulatory framework and can provide objective guidance for price negotiations. However, it is only one piece of the pricing puzzle, and numerous methodological and procedural issues related to DiGA pricing are still open. Thus, it remains to be seen to what extent DiGA prices will follow the premise of value-based pricing., (© 2022. The Author(s).)

Introduction: Several chronic underlying conditions (UCs) are known to be risk factors for developing herpes zoster (HZ) and to increase the severity of HZ and its risk of recurrence. The aim of this study was to investigate the incidence and recurrence of HZ in adult patients with one or multiple UCs., Methods: A retrospective cohort study based on claims data representing 13% of the statutory health insurance population from 2007 to 2018 in Germany was performed. Patients aged ≥ 18 years were included when at least one of the following UCs was diagnosed: asthma, chronic heart failure, chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), depression, diabetes mellitus type 1 or 2, and rheumatoid arthritis (RA). Exact matching was used to account for differences in the distribution of age and sex between the case and matched control cohorts. Multi-morbidity was considered in sensitivity analyses by analyzing patients with only one UC., Results: Patients with asthma, CHD, COPD, depression, and RA had, on average, a 30% increased risk of developing acute HZ compared to patients without any UC. RA was found to have the highest odds ratio among these conditions, varying from 1.37 to 1.57 for all age groups. Patients with depression also showed a high risk of developing HZ. Analysis of recurrence indicated that patients with at least one UC in the age groups 18-49 years and 50-59 years had the highest risk for a recurrent HZ. After experiencing a first recurrence, patients, regardless of age group, had a two- to threefold higher risk for a second recurrence., Conclusion: This study of representative claims data shows a higher HZ incidence and recurrence frequency in patients with UCs. These results provide relevant information for national health care guidelines and disease management programs.