In July 2023, the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic. This report summarizes the rich discussions that occurred during the workshop. The workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data, social media, and wastewater monitoring. Significant advancements were noted in the development of predictive models, with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease trends. The role of open collaboration between various stakeholders in modelling was stressed, advocating for the continuation of such partnerships beyond the pandemic. A major gap identified was the absence of a common international framework for data sharing, which is crucial for global pandemic preparedness. Overall, the workshop underscored the need for robust, adaptable modelling frameworks and the integration of different data sources and collaboration across sectors, as key elements in enhancing future pandemic response and preparedness. 

Redefining pandemic preparedness: Multidisciplinary insights from the CERP modelling workshop in infectious diseases, workshop report

COVID-19 can show a variable course, from asymptomatic infections to acute respiratory failure and death. For efficient allocation of resources, patients should be stratified according to their risk for a severe course as early as possible.135 hospitalized patients with COVID-19 pneumonia at four German hospitals were prospectively included in this observational study. A standardized clinical laboratory profile was taken at hospital admission and a panel of serum markers with possible roles in the COVID-associated cytokine storm were also determined. 112 patients could be evaluated. The primary endpoint of ventilator requirement or death within 30 days of symptom onset was met by 13 patients.Serum elevations of interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) at hospital admission were each highly significantly (p < 0.001) associated with ventilator requirement/death within 30 days of symptom onset. With a sensitivity of 92% and a specificity of 65–67%, IL-6 ≥ 52.8 pg/ml, PCT ≥ 0.11 ng/ml, and CRP ≥ 71.1 mg/L were predictive of a severe course of COVID-19. Positive likelihood ratios were between 2.6–2.8 and negative likelihood ratios were between 0.11–0.13 for these three markers.Negative likelihood ratios indicate that IL-6, PCT, and CRP at hospital admission can be used for identifying patients at low risk for severe COVID-19 progression.

Serum interleukin-6, procalcitonin, and C-reactive protein at hospital admission can identify patients at low risk for severe COVID-19 progression

Abstract Aim COVID-19 has been associated with cardiovascular complications including ventricular arrhythmias (VA) and an increased number of out-of-hospital cardiac arrests. Nevertheless, several authors described a decrease of VA burden in patients with an implantable defibrillator (ICD) during the first wave of the COVID-19 pandemic. The objective of this study was to determine if these observations could be transferred to later periods of the pandemic as well. Methods We retrospectively analyzed a total of 1674 patients with an ICD presenting in our outpatient clinic during the second wave of the COVID-19 pandemic and during a control period for the occurrence of VA requiring ICD interventions. Results Seven hundred ninety-five patients with an ICD had a device interrogation in our ambulatory clinic during the second wave of the COVID-19 pandemic compared to eight hundred seventy-nine patients in the control period. There was significant higher amount of adequate ICD therapies in the course of the COVID-19 period. Thirty-six patients (4.5%) received in total eighty-five appropriate ICD interventions during COVID-19, whereas only sixteen patients (1.8%) had sustained VA in the control period ( p = 0.01). Conclusion In contrast to the first wave of COVID-19, which was characterized by a decrease or least stable number of ICD therapies in several centers, we found a significant increase of VA in ICD patients during the second wave of COVID-19. Possible explanations for this observation include higher infectious rates, potential cardiac side effects of the vaccination as well as personal behavioral changes, or reduced utilization of medical services. 

Ventricular arrhythmia burden in ICD patients during the second wave of the COVID-19 pandemic.

The COVID-19 pandemic had a negative impact on the number of solid organ transplantations. After a global decline of 16% in 2020, their numbers subsequently returned to pre-pandemic levels. In contrast, numbers in Germany remained almost constant in 2020 and 2021 but fell by 6.9% in 2022. The reasons for this divergent development are unknown.The number of deceased with a severe brain damage, potential and utilized donors after braindeath and the intensive care unit treatment capacity were retrospectively compared for the years 2022 and 2021 at five university hospitals in North Rhine-Westphalia, Germany. Reasons for a donation not utilized were reviewed. To enable a comparison of the results with the whole of Germany and the pre-pandemic period, numbers of potential and utilized donors were extracted from official organ donation activity reports of all harvesting hospitals in Germany for the years 2019–2022.The numbers of deceased with a severe brain damage (−10%), potential (−9%), and utilized donors after braindeath (−44%), and intensive care unit treatment capacities (−7.2%) were significantly lower in 2022 than 2021. A COVID-19 infection was a rarer (−79%), but donor instability (+44%) a more frequent reason against donation in 2022, whereas preserved brain stem reflexes remained the most frequent reason in both years (54%). Overall numbers of potential and utilized donations in Germany were lower in 2022 than in the pre-pandemic period, but this was mainly due to lower numbers in hospitals of lower care. The number of potential donors in all university hospitals were higher in 2022 but utilized donations still lower than in 2019.The decrease in potential and utilized donations was a result of reduced intensive care unit treatment capacities and a lower conversion rate at the five university hospitals. A COVID-19 infection did not play a role in 2022. These results indicate that ICU treatment capacities must be restored to increase donations. The lower number of potential donors and the even lower conversion rate in 2022 throughout Germany show that restructuring the organ procurement process in Germany needs to be discussed to increase the number of donations.

Post-COVID-19 pandemic organ donation activities in Germany: a multicenter retrospective analysis

Given the crucial role of vaccination in halting the COVID-19 pandemic, it is imperative to understand the factors that motivate adolescents to get vaccinated. We surveyed adolescents and their accompanying guardians scheduled to receive a COVID-19 vaccination (Comirnaty) in an urban region in Germany in mid-2021 regarding their motivation for getting vaccinated and collected data on their sociodemographic characteristics, medical history, vaccination status, and any history of COVID-19 infection in the family. We also queried information strategies related to the SARS-CoV-2 pandemic. Motivations for getting vaccinated were similar among adolescents and their parents. The primary reasons for vaccination were protection against SARS-CoV-2-related illness and gaining access to leisure facilities. This was not influenced by gender, health status, migration background, or the presence of chronic or acute diseases. The percentage of parents who had received SARS-CoV-2 immunization and the proportion of parents with a high level of education were higher among study participants than in the general population. Adolescents were especially willing to be vaccinated if they came from a better educational environment and had a high vaccination rate in the family. Emphasizing the importance of vaccination among all segments of the population and removing barriers to vaccines may lead to an ameliorated acceptance of COVID-19 vaccines.

Motivations for Adolescent COVID-19 Vaccination: A Comparative Study of Adolescent and Caregiver Perspectives in Germany

The coronavirus disease 2019 (COVID-19) pandemic challenged many national health care systems, with hospitals reaching capacity limits of intensive care units (ICU). Thus, the estimation of acute local burden of ICUs is critical for appropriate management of health care resources. In this work, we applied non-linear mixed effects modeling to develop an epidemiological SARS-CoV-2 infection model for Germany, with its 16 federal states and 400 districts, that describes infections as well as COVID-19 inpatients, ICU patients with and without mechanical ventilation, recoveries, and fatalities during the first two waves of the pandemic until April 2021. Based on model analyses, covariates influencing the relation between infections and outcomes were explored. Non-pharmaceutical interventions imposed by governments were found to have a major impact on the spreading of SARS-CoV-2. Patient age and sex, the spread of variant B.1.1.7, and the testing strategy (number of tests performed weekly, rate of positive tests) affected the severity and outcome of recorded cases and could reduce the observed unexplained variability between the states. Modeling could reasonably link the discrepancies between fine-grained model simulations of the 400 German districts and the reported number of available ICU beds to coarse-grained COVID-19 patient distribution patterns within German regions.

/pdf/model-based-analysis-of-sars-cov-2-infections-2n92cqn8.pdf

Model-Based Analysis of SARS-CoV-2 Infections, Hospitalization and Outcome in Germany, the Federal States and Districts

In Germany, the incidence of cervical cancer, a disease caused by human papillomaviruses (HPV), is higher than in neighboring European countries. HPV vaccination has been recommended for girls since 2007. However, it continues to be significantly less well received than other childhood vaccines, so its potential for cancer prevention is not fully realized. To find new starting points for improving vaccination rates, we analyzed pseudonymized routine billing data from statutory health insurers in the PRÄZIS study (prevention of cervical carcinoma and its precursors in women in Saarland) in the federal state Saarland serving as a model region. We show that lowering the HPV vaccination age to 9 years led to more completed HPV vaccinations already in 2015. Since then, HPV vaccination rates and the proportion of 9- to 11-year-old girls among HPV-vaccinated females have steadily increased. However, HPV vaccination rates among 15-year-old girls in Saarland remained well below 50% in 2019. Pediatricians vaccinated the most girls overall, with a particularly high proportion at the recommended vaccination age of 9–14 years, while gynecologists provided more HPV catch-up vaccinations among 15-17-year-old girls, and general practitioners compensated for HPV vaccination in Saarland communities with fewer pediatricians or gynecologists. We also provide evidence for a significant association between attendance at the children´s medical check-ups “U11” or “J1” and HPV vaccination. In particular, participation in HPV vaccination is high on the day of U11. However, obstacles are that U11 is currently not financed by all statutory health insurers and there is a lack of invitation procedures for both U11 and J1, resulting in significantly lower participation rates than for the earlier U8 or U9 screenings, which are conducted exclusively with invitations and reminders. Based on our data, we propose to restructure U11 and J1 screening in Germany, with mandatory funding for U11 and organized invitations for HPV vaccination at U11 or J1 for both boys and girls.

/pdf/human-papillomavirus-vaccination-of-girls-in-the-german-1mz5env7.pdf

Human papillomavirus vaccination of girls in the German model region Saarland: Insurance data-based analysis and identification of starting points for improving vaccination rates

Objectives The study examined the impact of varying prescription requirements for phosphodiesterase-5 inhibitors (PDE-5is) on the management of erectile dysfunction (ED) in men. Methods A survey involving 10,000 men from Germany, Norway, Poland, and Switzerland was conducted using the International Index of Erectile Function Questionnaire to identify men with ED and interview them regarding their treatment and experiences. The use of PDE-5is by men without ED was also investigated. Results The proportion of PDE-5i users with ED was higher in Norway and Poland (over-the-counter availability) and Switzerland (prescribed by pharmacist) than that in Germany (doctor’s prescription required). Across all countries, men seeking to buy PDE-5is from pharmacies were advised to consult a doctor. The use of black market channels for purchasing PDE-5is was minimal in regions allowing non-prescription availability. The non-medical use was uncommon in all regions. Conclusion The need for a prescription for PDE-5is may hinder seeking treatment for ED and detecting underlying conditions. Therefore, PDE-5is should be approved as prescription-free medicines to improve the management of ED and to encourage men’s engagement with the healthcare system.

Exploring Patient Pathways and Care Situations in Men With Erectile Dysfunction in Different PDE-5 Inhibitor Regulatory Settings

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Model-Based Analysis of SARS-CoV-2 Infections, Hospitalization and Outcome in Germany, the Federal States and Districts

Human papillomavirus vaccination of girls in the German model region Saarland: Insurance data-based analysis and identification of starting points for improving vaccination rates

Exploring Patient Pathways and Care Situations in Men With Erectile Dysfunction in Different PDE-5 Inhibitor Regulatory Settings