Diagnostic test accuracy in longitudinal study settings: theoretical approaches with use cases from clinical practice.

OBJECTIVES: In this study, we evaluate how to estimate diagnostic test accuracy (DTA) correctly in the presence of longitudinal patient data (ie, repeated test applications per patient). STUDY DESIGN AND SETTING: We used a nonparametric approach to estimate the sensitivity and specificity of three tests for different target conditions with varying characteristics (ie, episode length and disease-free intervals between episodes): 1) systemic inflammatory response syndrome (n = 36), 2) depression (n = 33), and 3) epilepsy (n = 30). DTA was estimated on the levels 'time', 'block', and 'patient-time' for each diagnosis, representing different research questions. The estimation was conducted for the time units per minute, per hour, and per day. RESULTS: A comparison of DTA per and across use cases showed variations in the estimates, which resulted from the used level, the time unit, the resulting number of observations per patient, and the diagnosis-specific characteristics. Intra- and inter-use-case comparisons showed that the time-level had the highest DTA, particularly the larger the time unit, and that the patient-time-level approximated 50% sensitivity and specificity. CONCLUSION: Researchers need to predefine their choices (ie, estimation levels and time units) based on their individual research aims, estimands, and diagnosis-specific characteristics of the target outcomes to make sure that unbiased and clinically relevant measures are communicated. In cases of uncertainty, researchers could report the DTA of the test using more than one estimation level and/or time unit.

Personality and the use of cancer screenings - Results of the German National Cohort.

Objective: To determine the association between personality characteristics and use of different cancer screenings. Methods: We used data from the German National Cohort (NAKO; mean age was 53.0 years (SD: 9.2 years)) - a population-based cohort study. A total of 132,298 individuals were included in the analyses. As outcome measures, we used (self-reported): stool examination for blood (haemoccult test, early detection of bowel cancer), colonoscopy (screening for colorectal cancer), skin examination for moles (early detection of skin cancer), breast palpation by a doctor (early detection of breast cancer), x-ray examination of the breast ("mammography", early detection of breast cancer), cervical smear test, finger examination of the rectum (early detection of prostate cancer), and blood test for prostate cancer (determination of Prostate-Specific Antigen level). The established Big Five Inventory-SOEP was used to quantify personality factors. It was adjusted for several covariates based on the Andersen model. Unadjusted and adjusted multiple logistic regressions were computed. Results: A higher probability of having a skin examination for moles, for example, was associated with a higher conscientiousness (OR: 1.07, p < 0.001), higher extraversion (OR: 1.03, p < 0.001), higher agreeableness (OR: 1.02, p < 0.001), lower openness to experience (OR: 0.98, p < 0.001) and higher neuroticism (OR: 1.07, p < 0.001) among the total sample. Depending on the outcome used, the associations slightly varied. Conclusions: Particularly higher levels of extraversion, neuroticism and conscientiousness are associated with the use of different cancer screenings. Such knowledge may help to better understand non-participation in cancer screening examinations from a psychological perspective.

Changes in physical activity and sedentary behavior during the first COVID-19 pandemic- restrictions in Germany: a nationwide survey : Running head: physical activity during the COVID-19 restrictions.

BACKGROUND: The COVID-19 pandemic restrictions posed challenges to maintaining healthy lifestyles and physical well-being. During the first mobility restrictions from March to mid-July 2020, the German population was advised to stay home, except for work, exercise, and essential shopping. Our objective was to comprehensively assess the impact of these restrictions on changes in physical activity and sedentary behavior to identify the most affected groups. METHODS: Between April 30, 2020, and May 12, 2020, we distributed a COVID-19-specific questionnaire to participants of the German National Cohort (NAKO). This questionnaire gathered information about participants' physical activity and sedentary behavior currently compared to the time before the restrictions. We integrated this new data with existing information on anxiety, depressive symptoms, and physical activity. The analyses focused on sociodemographic factors, social relationships, physical health, and working conditions. RESULTS: Out of 152,421 respondents, a significant proportion reported altered physical activity and sedentary behavioral patterns due to COVID-19 restrictions. Over a third of the participants initially meeting the WHO's physical activity recommendation could no longer meet the guidelines during the restrictions. Participants reported substantial declines in sports activities (mean change (M) = -0.38; 95% CI: -.390; -.378; range from -2 to + 2) and reduced active transportation (M = -0.12; 95% CI: -.126; -.117). However, they also increased recreational physical activities (M = 0.12; 95% CI: .117; .126) while engaging in more sedentary behavior (M = 0.24; 95% CI: .240; .247) compared to pre-restriction levels. Multivariable linear and log-binomial regression models indicated that younger adults were more affected by the restrictions than older adults. The shift to remote work, self-rated health, and depressive symptoms were the factors most strongly associated with changes in all physical activity domains, including sedentary behavior, and the likelihood to continue following the physical activity guidelines. CONCLUSIONS: Mobility patterns shifted towards inactivity or low-intensity activities during the nationwide restrictions in the spring of 2020, potentially leading to considerable and lasting health risks.

Radiological assessment of periodontal ligament space visibility on third molars for forensic age assessment - a comparison study of three different staging scales.

Various staging scales have been proposed for the assessment of the visibility of the periodontal ligament space of mandibular third molars on dental panoramic radiographs (PANs) for forensic age assessment in living individuals. However, up to now, there has been no systematic comparison between these staging scales available. We directly compared the 2010 staging scale proposed by Olze et al. with the 2017 staging by Lucas et al. and the 2020 staging by Guo et al. in a German study population. We evaluated 233 PANs from 115 females and 118 males aged 20.0 to 40.9 years using three independent examiners, with one examiner conducting two assessments. We examined the correlation between age and stage, as well as the inter- and intra-rater reliabilities. While the point estimates for the correlation coefficient and the reliability measures were lowest for the Guo scale and highest for the Olze scale, confidence intervals showed a large overlap, particularly for the scales of Olze et al. and Lucas et al. The correlation coefficients between stage and age were consistently lower in females than in males across all methods. In summary, we showed that the staging scales of Olze et al. and Lucas et al. were very similar. The Olze method showed higher point estimates across all analyses, and because there are more reference data available for this method, we argue that it should be preferred as the method of choice for further studies in the field. However, Guo method could be considered for instances, in which the inter-radicular periodontal ligament is not evaluable.

Differences in Anthropometric Measures Based on Sex, Age, and Health Status: Findings From the German National Cohort (NAKO).

BACKGROUND: Obesity is a worldwide health problem. We conducted detailed analyses of anthropometric measures in a comprehensive, population-based, current cohort in Germany. METHODS: In the German National Cohort (NAKO), we analyzed cross-sectional data on body-mass index (BMI), waist and hip circumference, subcutaneous (SAT) and visceral adipose tissue (VAT) as measured by ultrasound, and body fat percentage. The data were stratified by sex, age, and self-reported physicians' diagnoses of cardiovascular diseases (CVD), metabolic diseases (MetD), cardiometabolic diseases (CMD), and cancer. RESULTS: Data were available from 204 751 participants (age, 49.9 ± 12.8 years; 50.5% women). Body size measures generally increased with age. Men had a higher BMI, larger waist circumference, and more VAT than women, while women had a larger hip circumference, more SAT, and a higher body fat percentage than men. For example, the mean BMI of participants over age 60 was 28.3 kg/m2 in men and 27.6 kg/m2 in women. CVD, MetD, and CMD were associated with higher anthropometric values, while cancer was not. For example, the mean BMI was 25.3 kg/m2 in healthy women, 29.4 kg/m2 in women with CMD, and 25.4 kg/m2 in women with cancer. CONCLUSION: Obesity is widespread in Germany, with notable differences between the sexes in anthropometric values. Obesity was more common in older participants and those with chronic diseases other than cancer. Elevated values were especially common in multimorbid individuals.

The impact of inaccurate assumptions about antibody test accuracy on the parametrisation and results of infectious disease models of epidemics.

The parametrisation of infectious disease models is often done based on epidemiological studies that use diagnostic and serology tests to establish disease prevalence or seroprevalence in the population being modelled. During outbreaks of an emerging infectious disease, tests are often used, both for disease control and epidemiological studies, before studies evaluating their accuracy in the population have concluded, with assumptions made about accuracy parameters like sensitivity and specificity. In this simulation study, we simulated such an outbreak, based on the case study of COVID-19, and found that inaccurate parametrisation of infectious disease models due to assumptions about antibody test accuracy in a seroprevalence study can cause modelling results that inform public health decisions to be inaccurate; for example, in our simulation setup, assuming that antibody test specificity was 0.99 instead of 0.90 when it was in fact 0.90 led to an average relative difference of 0.78 in model-projected peak hospitalisations, even when test sensitivity and all other parameters were accurately characterised. We therefore suggest that methods to speed up test evaluation studies are vitally important in the public health response to an emerging outbreak.

Isolating the effect of confounding from the observed survival benefit of screening participants - a methodological approach illustrated by data from the German mammography screening programme.

BACKGROUND: Mammography screening programmes (MSP) aim to reduce breast cancer mortality by shifting diagnoses to earlier stages. However, it is difficult to evaluate the effectiveness of current MSP because analyses can only rely on observational data, comparing women who participate in screening with women who do not. These comparisons are subject to several biases: one of the most important is self-selection into the MSP, which introduces confounding and is difficult to control for. Here, we propose an approach to quantify confounding based on breast cancer survival analyses using readily available routine data sources. METHODS: Using data from the Cancer Registry of North Rhine-Westphalia, Germany, we estimate the relative contribution of confounding to the observed survival benefit of participants of the German MSP. This is accomplished by comparing non-participants, participants with screen-detected and participants with interval breast cancers for the endpoints "death from breast cancer" and "death from all causes other than breast cancer" - the latter being assumed to be unrelated to any MSP effect. By using different contrasts, we eliminate the effects of stage shift, lead and length time bias. The association of breast cancer detection mode with survival is analysed using Cox models in 68,230 women, aged 50-69 years, with breast cancer diagnosed in 2006-2014 and followed up until 2018. RESULTS: The hazard of dying from breast cancer was lower in participants with screen-detected cancer than in non-participants (HR = 0.21, 95% CI: 0.20-0.22), but biased by lead and length time bias, and confounding. When comparing participants with interval cancers and non-participants, the survival advantage was considerably smaller (HR = 0.62, 95% CI: 0.58-0.66), due to the elimination of stage shift and lead time bias. Finally, considering only mortality from causes other than breast cancer in the latter comparison, length time bias was minimised, but a survival advantage was still present (HR = 0.63, 95% CI: 0.56-0.70), which we attribute to confounding. CONCLUSIONS: This study shows that, in addition to stage shift, lead and length time bias, confounding is an essential component when comparing the survival of MSP participants and non-participants. We further show that the confounding effect can be quantified without explicit knowledge of potential confounders by using a negative control outcome.

Regional patient transfer patterns matter for the spread of hospital-acquired pathogens.

Pathogens typically responsible for hospital-acquired infections (HAIs) constitute a major threat to healthcare systems worldwide. They spread via hospital (or hospital-community) networks by readmissions or patient transfers. Therefore, knowledge of these networks is essential to develop and test strategies to mitigate and control the HAI spread. Until now, no methods for comparing healthcare networks across different systems were proposed. Based on healthcare insurance data from four German federal states (Bavaria, Lower Saxony, Saxony and Thuringia), we constructed hospital networks and compared them in a systematic approach regarding population, hospital characteristics, and patient transfer patterns. Direct patient transfers between hospitals had only a limited impact on HAI spread. Whereas, with low colonization clearance rates, readmissions to the same hospitals posed the biggest transmission risk of all inter-hospital transfers. We then generated hospital-community networks, in which patients either stay in communities or in hospitals. We found that network characteristics affect the final prevalence and the time to reach it. However, depending on the characteristics of the pathogen (colonization clearance rate and transmission rate or even the relationship between transmission rate in hospitals and in the community), the studied networks performed differently. The differences were not large, but justify further studies.

Childhood Trauma and Somatic and Mental Illness in Adulthood.

BACKGROUND: Childhood trauma is associated with somatic and mental illness in adulthood. The strength of the association varies as a function of age, sex, and type of trauma. Pertinent studies to date have mainly focused on individual diseases. In this study, we investigate the association between childhood trauma and a multiplicity of somatic and mental illnesses in adulthood. METHODS: Data from 156 807 NAKO Health Study participants were analyzed by means of logistic regressions, with adjustment for age, sex, years of education, and study site. The Childhood Trauma Screener differentiated between no/minor (n = 115 891) and moderate/severe childhood trauma (n = 40 916). The outcome variables were medical diagnoses of five somatic and two mental health conditions as stated in the clinical history. RESULTS: Persons with childhood trauma were more likely to bear a diagnosis of all of the studied conditions: cancer (odds ratio [OR] = 1.10; 95% confidence interval: [1.05; 1.15]), myocardial infarction (OR = 1.13 [1.03; 1.24]), diabetes (OR = 1.16, [1.10; 1.23]), stroke (OR = 1.35 [1.23; 1.48]), chronic obstructive pulmonary disease (OR = 1.45 [1.38; 1.52]), depression (OR = 2.36 [2.29; 2.43]), and anxiety disorders (OR = 2.08 [2.00; 2.17]). All of these associations were stronger in younger persons, regardless of the nature of childhood trauma. Differences between the sexes were observed only for some of these associations. CONCLUSION: Childhood trauma was associated with a higher probability of developing mental as well as somatic illness in adulthood. As childhood trauma is an element of individual history that the victim has little to no control over, and because the illnesses that can arise in adulthood in association with it are a heavy burden on the affected persons and on society, there is a need for research on these associations and for the development of preventive measures.

Dental age assessment in the living: a comparison of two common stage classifications for assessing radiographic visibility of the root canals in mandibular third molars.

After dentition is complete, degenerative tooth characteristics can be used for dental age assessment. Radiological assessment of the visibility of the root canals of the mandibular third molars in dental panoramic radiographs (DPRs) is known to be one such suitable feature. Essentially, two different stage classifications are available for evaluating the visibility of the root canals of mandibular third molars in the DPR. The aim of this study was to determine if one method outperforms the other. Therefore, the 2010 method of Olze et al. was directly compared to the 2017 method of Lucas et al. in the 2020 modification of Al Qattan et al. To this end, 233 DPRs from 116 females and 117 males aged 20.0 to 40.9 years were evaluated by three independent experienced examiners. In addition, one examiner ran two independent evaluations. Correlation between age and stage was investigated, and the inter- and intra-rater reliability was estimated for both methods. Correlation between age and stage was higher with the Olze method (Spearman rho 0.388 [95% CI 0.309, 0.462], males and 0.283 [95% CI 0.216, 0.357], females) than the Lucas method (0.212 [95% CI 0.141, 0.284], males and 0.265 [95% CI 0.193, 0.340], females). The intra-rater repeatability of the Olze method (Krippendorff's α = 0.576 [95% CI 0.508, 0.644], males and α = 0.592 [95% CI 0.523, 0.661], females) was greater than that for the Lucas method (intra-rater α = 0.422 [95% CI 0.382, 0.502], males and α = 0.516 [95% CI 0.523, 0.661], females). Inter-rater reproducibility was also greater for the Olze method (α = 0.542 [95% CI 0.463, 0.620], males and α = 0.533 [95% CI 0.451, 0.615], females) compared to the Lucas method (α = 0.374 [95% CI 0.304, 0.443], males and α = 0.432 [95% CI 0.359, 0.505], females). The method of Olze et al. was found to present marginal advantages to the Lucas et al. method across all examinations and may be a more appropriate method for application in future studies.

Bridging the gap - estimation of 2022/2023 SARS-CoV-2 healthcare burden in Germany based on multidimensional data from a rapid epidemic panel.

OBJECTIVES: Throughout the SARS-CoV-2 pandemic, Germany like other countries lacked adaptive population-based panels to monitor the spread of epidemic diseases. METHODS: To fill a gap in population-based estimates needed for winter 2022/23 we resampled in the German SARS-CoV-2 cohort study MuSPAD in mid-2022, including characterization of systemic cellular and humoral immune responses by interferon-γ-release assay (IGRA) and CLIA/IVN assay. We were able to confirm categorization of our study population into four groups with differing protection levels against severe COVID-19 courses based on literature synthesis. Using these estimates, we assessed potential healthcare burden for winter 2022/23 in different scenarios with varying assumptions on transmissibility, pathogenicity, new variants, and vaccine booster campaigns in ordinary differential equation models. RESULTS: We included 9921 participants from eight German regions. While 85% of individuals were located in one of the two highest protection categories, hospitalization estimates from scenario modeling were highly dependent on viral variant characteristics ranging from 30-300% compared to the 02/2021 peak. Our results were openly communicated and published to an epidemic panel network and a newly established modeling network. CONCLUSIONS: We demonstrate feasibility of a rapid epidemic panel to provide complex immune protection levels for inclusion in dynamic disease burden modeling scenarios.

Early steroids after pediatric liver transplantation protect against T-cell-mediated rejection: Results from the ChilSFree study.

Steroid-free immunosuppression protocols gained popularity in pediatric liver transplantation (pLT) after the introduction of IL-2-receptor blockade for induction therapy. We analyzed the clinical and immunologic outcome data of the multicenter prospective observational ChilSFree study to compare the impact of steroid-free versus steroid-containing immunosuppressive therapy following pLT in a real-life scenario. Two hundred forty-six children [55.3% male, age at pLT median: 2.4 (range: 0.2-17.9) y] transplanted for biliary atresia (43%), metabolic liver disease (9%), acute liver failure (4%), hepatoblastoma (9%), and other chronic end-stage liver diseases (39%) underwent immune monitoring and clinical data documentation over the first year after pLT. Patient and graft survival at 1 year was 98.0% and 92.7%, respectively. Primary immunosuppression was basiliximab induction followed by tacrolimus (Tac) monotherapy (55%), Tac plus steroid tapering over 3 months (29%), or cyclosporine and steroid tapering (7%). One center used intraoperative steroids instead of basiliximab followed by Tac plus mycophenolate mofetil (7% of patients). N = 124 biopsy-proven T-cell-mediated rejections were documented in n = 82 (33.3%) patients. T-cell-mediated rejection occurred early (median: 41 d, range: 3-366 d) after pLT. Patients initially treated with Tac plus steroids experienced significantly fewer episodes of rejection than patients treated with Tac alone (chi-square p <0.01). The use of steroids was associated with earlier downregulation of proinflammatory cytokines interferon (IFN)-γ, Interleukin (IL)-6, CX motif chemokin ligand (CXCL)8, IL-7, and IL-12p70. Both primary immunosuppression with Tac plus steroids and living donor liver transplantation were independent predictors of rejection-free survival 1 year after pLT on logistic regression analysis. Adjunctive steroid therapy after pLT leads to earlier suppression of the post-pLT proinflammatory response and significantly reduced rejection rates during the first year after pLT (15.9%). Fifty-one percent of patients initially treated without steroids remain steroid-free over the first 12 months without rejection.

Effect of SARS-CoV-2 Incidence and Immunisation Rates on Sporadic Creutzfeldt-Jakob Disease Incidence.

BACKGROUND: Recent case studies and media outlets have hypothesised an effect of SARS-CoV-2 infection and immunisation on the development or progression of neurodegenerative diseases such as Alzheimer's disease or sporadic Creutzfeldt-Jakob disease (sCJD). OBJECTIVES: This study aims to identify potential associations of SARS-CoV-2 infections and SARS-CoV-2 immunisation with sCJD incidence, disease duration, and age of onset. METHOD: We used data from a prospective sCJD surveillance study in Germany (2016-2022) and publicly available datasets of SARS-CoV-2 cases and vaccination numbers in Germany for the years 2020-2022. Associations of SARS-CoV-2 incidence and immunisation rates with sCJD incidence were assessed by comparing quarterly and annual cumulative sCJD incidences in the periods before (2016-2019) and during the pandemic (2020-2022). RESULTS: We could not identify any time-related effect of SARS-CoV-2 incidence or immunisation rate on the sCJD incidence. Moreover, we did not find any sCJD incidence alterations before and during the SARS-CoV-2 pandemic on a federal or state level. The overall sCJD incidence was within expected ranges in the years 2020-2022. There were no changes in age of onset and clinical disease duration in these years. CONCLUSIONS: We found no evidence supporting a short-term effect of the pandemic on sCJD incidence. However, considering the extended pre-clinical phase of sCJD, continued surveillance is needed to identify potential future incidence alterations.

Seropositivity of Borrelia burgdorferi s.l. in Germany-an analysis across four German National Cohort (NAKO) study sites.

Lyme borreliosis (LB) is caused by the transmission of Borrelia burgdorferi s.l. from ticks to humans. Climate affects tick abundance, and climate change is projected to promote shifts in abundance in Europe, potentially increasing human exposure. We analyzed serum samples collected between the years 2014-2019 from German National Cohort (NAKO) participants at four study sites (Augsburg, Berlin, Hanover, Münster) for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies using an enzyme-linked immunosorbent assay (ELISA) and line blot immunoassay as confirmatory test for positive and equivocal ELISA samples. We reported crude and weighted seropositivity proportions for local estimates. We used mixed model analysis to investigate associated factors, such as age, sex, migration background, or animal contacts. We determined the serostatus of 14,207 participants. The weighted seropositivity proportions were 3.4% (IgG) and 0.4% (IgM) in Augsburg, 4.1% (IgG) and 0.6% (IgM) in northern Berlin, 3.0% (IgG) and 0.9% (IgM) in Hanover, and 2.7% (IgG) and 0.6% (IgM) in Münster. We found higher odds for IgG seropositivity with advancing age (p < 0.001), among males compared to females (p < 0.001) and reduced odds among participants with migration background compared to those without (p = 0.001). We did not find evidence for an association between serostatus and depression, children within the household, or animal contact, respectively. We found low seropositivity proportions and indications of differences across the study locations, although between-group comparisons did not yield significant results. Comparisons to earlier research are subject to important limitations; however, our results indicate no major increases in seropositivity over time. Nevertheless, monitoring of seropositivity remains critical in light of potential climate-related Borrelia exposure.

Transmission of drug-resistant bacteria in a hospital-community model stratified by patient risk.

A susceptible-infectious-susceptible (SIS) model for simulating healthcare-acquired infection spread within a hospital and associated community is proposed. The model accounts for the stratification of in-patients into two susceptibility-based risk groups. The model is formulated as a system of first-order ordinary differential equations (ODEs) with appropriate initial conditions. The mathematical analysis of this system is demonstrated. It is shown that the system has unique global solutions, which are bounded and non-negative. The basic reproduction number ([Formula: see text]) for the considered model is derived. The existence and the stability of the stationary solutions are analysed. The disease-free stationary solution is always present and is globally asymptotically stable for [Formula: see text], while for [Formula: see text] it is unstable. The presence of an endemic stationary solution depends on the model parameters and when it exists, it is globally asymptotically stable. The endemic state encompasses both risk groups. The endemic state within only one group only is not possible. In addition, for [Formula: see text] a forward bifurcation takes place. Numerical simulations, based on the anonymised insurance data, are also presented to illustrate theoretical results.

Estimating fine age structure and time trends in human contact patterns from coarse contact data: The Bayesian rate consistency model.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), large-scale social contact surveys are now longitudinally measuring the fundamental changes in human interactions in the face of the pandemic and non-pharmaceutical interventions. Here, we present a model-based Bayesian approach that can reconstruct contact patterns at 1-year resolution even when the age of the contacts is reported coarsely by 5 or 10-year age bands. This innovation is rooted in population-level consistency constraints in how contacts between groups must add up, which prompts us to call the approach presented here the Bayesian rate consistency model. The model can also quantify time trends and adjust for reporting fatigue emerging in longitudinal surveys through the use of computationally efficient Hilbert Space Gaussian process priors. We illustrate estimation accuracy on simulated data as well as social contact data from Europe and Africa for which the exact age of contacts is reported, and then apply the model to social contact data with coarse information on the age of contacts that were collected in Germany during the COVID-19 pandemic from April to June 2020 across five longitudinal survey waves. We estimate the fine age structure in social contacts during the early stages of the pandemic and demonstrate that social contact intensities rebounded in an age-structured, non-homogeneous manner. The Bayesian rate consistency model provides a model-based, non-parametric, computationally tractable approach for estimating the fine structure and longitudinal trends in social contacts and is applicable to contemporary survey data with coarsely reported age of contacts as long as the exact age of survey participants is reported.

SARS-CoV-2 sero-immunity and quality of life in children and adolescents in relation to infections and vaccinations: the IMMUNEBRIDGE KIDS cross-sectional study, 2022.

PURPOSE: The study evaluates the effects on sero-immunity, health status and quality of life of children and adolescents after the upsurge of the Omicron variant in Germany. METHODS: This multicenter cross-sectional study (IMMUNEBRIDGE Kids) was conducted within the German Network University Medicine (NUM) from July to October 2022. SARS-CoV-2- antibodies were measured and data on SARS-CoV-2 infections, vaccinations, health and socioeconomic factors as well as caregiver-reported evaluation on their children's health and psychological status were assessed. RESULTS: 497 children aged 2-17 years were included. Three groups were analyzed: 183 pre-schoolchildren aged 2-4 years, 176 schoolchildren aged 5-11 years and 138 adolescents aged 12-18 years. Positive antibodies against the S- or N-antigen of SARS-CoV-2 were detected in 86.5% of all participants (70.0% [128/183] of pre-schoolchildren, 94.3% of schoolchildren [166/176] and 98.6% of adolescents [136/138]). Among all children, 40.4% (201/497) were vaccinated against COVID-19 (pre-schoolchildren 4.4% [8/183], schoolchildren 44.3% [78/176] and adolescents 83.3% [115/138]). SARS-CoV-2 seroprevalence was lowest in pre-school. Health status and quality of life reported by the parents were very positive at the time of the survey (Summer 2022). CONCLUSION: Age-related differences on SARS-CoV-2 sero-immunity could mainly be explained by differences in vaccination rates based on the official German vaccination recommendations as well as differences in SARS-CoV-2 infection rates in the different age groups. Health status and quality of life of almost all children were very good independent of SARS-CoV-2 infection and/or vaccination. TRIAL REGISTRATION: German Registry for Clinical Trials Identifier Würzburg: DRKS00025546 (registration: 11.09.2021), Bochum: DRKS00022434 (registration:07.08.2020), Dresden: DRKS 00022455 (registration: 23.07.2020).

Immunity Against SARS-CoV-2 in the German Population.

BACKGROUND: Early during the SARS-CoV-2 pandemic, national population-based seroprevalence surveys were conducted in some countries; however, this was not done in Germany. In particular, no seroprevalence surveys were planned for the summer of 2022. In the context of the IMMUNEBRIDGE project, the GUIDE study was carried out to estimate seroprevalence on the national and regional levels. METHODS: To obtain an overview of the population-wide immunity against SARS-CoV-2 among adults in Germany that would be as statistically robust as possible, serological tests were carried out using self-sampling dried blood spot cards in conjunction with surveys, one by telephone and one online. Blood samples were analyzed for the presence of antibodies to the S and N antigens of SARS-CoV-2. RESULTS: Among the 15 932 participants, antibodies to the S antigen were detected in 95.7%, and to the N antigen in 44.4%. In the higher-risk age groups of persons aged 65 and above and persons aged 80 and above, anti-S antibodies were found in 97,4% and 98.8%, respectively. Distinct regional differences in the distribution of anti-S and anti-N antibodies emerged. Immunity gaps were found both regionally and in particular subgroups of the population. High anti-N antibody levels were especially common in eastern German states, and high anti-S antibody levels in western German states. CONCLUSION: These findings indicate that a large percentage of the adult German population has formed antibodies against the SARS-CoV-2 virus. This will markedly lower the probability of an overburdening of the health care system by hospitalization and high occupancy of intensive care units due to future SARS-CoV-2 waves, depending on the viral characteristics of then prevailing variants.

Effect of risk status for severe COVID-19 on individual contact behaviour during the SARS-CoV-2 pandemic in 2020/2021-an analysis based on the German COVIMOD study.

BACKGROUND: One of the primary aims of contact restriction measures during the SARS-CoV-2 pandemic has been to protect people at increased risk of severe disease from the virus. Knowledge about the uptake of contact restriction measures in this group is critical for public health decision-making. We analysed data from the German contact survey COVIMOD to assess differences in contact patterns based on risk status, and compared this to pre-pandemic data to establish whether there was a differential response to contact reduction measures. METHODS: We quantified differences in contact patterns according to risk status by fitting a generalised linear model accounting for within-participant clustering to contact data from 31 COVIMOD survey waves (April 2020-December 2021), and estimated the population-averaged ratio of mean contacts of persons with high risk for a severe COVID-19 outcome due to age or underlying health conditions, to those without. We then compared the results to pre-pandemic data from the contact surveys HaBIDS and POLYMOD. RESULTS: Averaged across all analysed waves, COVIMOD participants reported a mean of 3.21 (95% confidence interval (95%CI) 3.14,3.28) daily contacts (truncated at 100), compared to 18.10 (95%CI 17.12,19.06) in POLYMOD and 28.27 (95%CI 26.49,30.15) in HaBIDS. After adjusting for confounders, COVIMOD participants aged 65 or above had 0.83 times (95%CI 0.79,0.87) the number of contacts as younger age groups. In POLYMOD, this ratio was 0.36 (95%CI 0.30,0.43). There was no clear difference in contact patterns due to increased risk from underlying health conditions in either HaBIDS or COVIMOD. We also found that persons in COVIMOD at high risk due to old age increased their non-household contacts less than those not at such risk after strict restriction measures were lifted. CONCLUSIONS: Over the course of the SARS-CoV-2 pandemic, there was a general reduction in contact numbers in the German population and also a differential response to contact restriction measures based on risk status for severe COVID-19. This differential response needs to be taken into account for parametrisations of mathematical models in a pandemic setting.