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The number of older adults worldwide is growing exponentially. However, while living longer, older individuals are more susceptible to both non-infectious and infectious diseases, at least in part due to alterations of the immune system. Here, we report on a prospective cohort study investigating the influence of age on immune responses and susceptibility to infection. The RESIST Senior Individuals (SI) cohort was established as a general population cohort with a focus on the elderly, enrolling an age- and sex-stratified sample of 650 individuals (n = 100 20-39y, n = 550 61-94y, 2019-2023, Hannover, Germany). It includes clinical, demographic, and lifestyle data and also extensive biomaterial sampling. Initial insights indicate that the SI cohort exhibits characteristics of the aging immune system and the associated susceptibility to infection, thereby providing a suitable platform for the decoding of age-related alterations of the immune system and unraveling the molecular mechanisms underlying the impaired immune responsiveness in aging populations by exploring comprehensive, unbiased multi-omics datasets., (© 2024. The Author(s).)

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., (© 2023. The Author(s).)

Background: The European Working Group on Sarcopenia in Older People (EWGSOP) updated in 2018 the cut-off points for low grip strength to assess sarcopenia based on pooled data from 12 British studies., Objective: Comparison of the EWGSOP2 cut-off points for low grip strength to those derived from a large German sample., Methods: We assessed the grip strength distribution across age and derived low grip strength cut-off points for men and women (peak mean -2.5 × SD) based on 200,389 German National Cohort (NAKO) participants aged 19-75 years. In 1,012 Cooperative Health Research in the Region of Augsburg (KORA)-Age participants aged 65-93 years, we calculated the age-standardised prevalence of low grip strength and time-dependent sensitivity and specificity for all-cause mortality., Results: Grip strength increased in the third and fourth decade of life and declined afterwards. Calculated cut-off points for low grip strength were 29 kg for men and 18 kg for women. In KORA-Age, the age-standardised prevalence of low grip strength was 1.5× higher for NAKO-derived (17.7%) compared to EWGSOP2 (11.7%) cut-off points. NAKO-derived cut-off points yielded a higher sensitivity and lower specificity for all-cause mortality., Conclusions: Cut-off points for low grip strength from German population-based data were 2 kg higher than the EWGSOP2 cut-off points. Higher cut-off points increase the sensitivity, thereby suggesting an intervention for more patients at risk, while other individuals might receive additional diagnostics/treatment without the urgent need. Research on the effectiveness of intervention in patients with low grip strength defined by different cut-off points is needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The eResearch system "Prospective Monitoring and Management App (PIA)" allows researchers to implement questionnaires on any topic and to manage biosamples. Currently, we use PIA in the longitudinal study ZIFCO (Integrated DZIF Infection Cohort within the German National Cohort) in Hannover (Germany) to investigate e.g. associations of risk factors and infectious diseases. Our aim was to assess user acceptance and compliance to determine suitability of PIA for epidemiological research on transient infectious diseases., Methods: ZIFCO participants used PIA to answer weekly questionnaires on health status and report spontaneous onset of symptoms. In case of symptoms of a respiratory infection, the app requested participants to self-sample a nasal swab for viral analysis. To assess user acceptance, we implemented the System Usability Scale (SUS) and fitted a linear regression model on the resulting score. For investigation of compliance with submitting the weekly health questionnaires, we used a logistic regression model with binomial response., Results: We analyzed data of 313 participants (median age 52.5 years, 52.4% women). An average SUS of 72.0 reveals good acceptance of PIA. Participants with a higher technology readiness score at the beginning of study participation also reported higher user acceptance. Overall compliance with submitting the weekly health questionnaires showed a median of 55.7%. Being female, of younger age and being enrolled for a longer time decreased the odds to respond. However, women over 60 had a higher chance to respond than women under 60, while men under 40 had the highest chance to respond. Compliance with nasal swab self-sampling was 77.2%., Discussion: Our findings show that PIA is suitable for the use in epidemiologic studies with regular short questionnaires. Still, we will focus on user engagement and gamification for the further development of PIA to help incentivize regular and long-term participation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ortmann 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.)

SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection against infection. The novel variant of concern (VoC) Omicron BA.1 and its sub-lineages have the largest number of amino acid alterations in its Spike protein to date. Thus, they may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals in particular in those who have only received a primary immunization scheme. We analyzed neutralization activity of sera from individuals after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe by in vitro neutralization assay at peak response towards SARS-CoV-2 B.1, Omicron sub-lineages BA.1, BA.2, BA.2.12.1, BA.3, BA.4/5, Beta and Delta pseudotypes and also provide longitudinal follow-up data from BNT162b2 vaccinees. All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (96-100%) towards the SARS-CoV-2 B.1 isolate, and minor to moderate reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant and its sub-lineages had the biggest impact, both in terms of response rates and neutralization titers. Only mRNA-1273 showed a 100% response rate to Omicron BA.1 and induced the highest level of neutralizing antibody titers, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination, vector-based AZD1222 and Ad26.CoV2.S performed less well with peak responder rates of 48%, 56% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up indicating that individuals with cross-protection against Omicron maintain it over time. Overall, our data strongly argue for booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based primary immunization scheme., (© 2022. The Author(s).)

Lyme borreliosis is the leading tick-related illness in Europe, caused by Borrelia Burgdorferi s.l. Lower Saxony, Germany, including its capital, Hanover, has a higher proportion of infected ticks than central European countries, justifying a research focus on the potential human consequences. The current knowledge gap on human incident infections, particularly in Western Germany, demands serological insights, especially regarding a potentially changing climate-related tick abundance and activity. We determined the immunoglobulin G (IgG) and immunoglobulin M (IgM) serostatuses for 8009 German National Cohort (NAKO) participants from Hanover, examined in 2014-2018. We used an enzyme-linked immunosorbent assay (ELISA) as the screening and a line immunoblot as confirmation for the Borrelia Burgdorferi s.l. antibodies. We weighted the seropositivity proportions to estimate general population seropositivity and estimated the force of infection (FOI). Using logistic regression, we investigated risk factors for seropositivity. Seropositivity was 3.0% (IgG) and 2.1% (IgM). The FOI varied with age, sharply increasing in participants aged ≥40 years. We confirmed advancing age and male sex as risk factors. We reported reduced odds for seropositivity with increasing body mass index and depressive symptomatology, respectively, pointing to an impact of lifestyle-related behaviors. The local proportion of seropositive individuals is comparable to previous estimates for northern Germany, indicating a steady seroprevalence.

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19-74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2-3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4-5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years., (© 2022. The Author(s).)

Recent increases in SARS-CoV-2 infections have led to questions about duration and quality of vaccine-induced immune protection. While numerous studies have been published on immune responses triggered by vaccination, these often focus on studying the impact of one or two immunisation schemes within subpopulations such as immunocompromised individuals or healthcare workers. To provide information on the duration and quality of vaccine-induced immune responses against SARS-CoV-2, we analyzed antibody titres against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and variants of concern in samples from a large German population-based seroprevalence study (MuSPAD) who had received all currently available immunisation schemes. We found that homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was particularly concerning with reduced titres and 91.7% of samples classified as non-responsive for ACE2 binding inhibition, suggesting that recipients require a booster mRNA vaccination. While mRNA vaccination induced a higher ratio of RBD- and S1-targeting antibodies, vector-based vaccines resulted in an increased proportion of S2-targeting antibodies. Given the role of RBD- and S1-specific antibodies in neutralizing SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why these vaccines have increased efficacy compared to vector-based formulations. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received, which could aid future dose allocation should shortages arise for certain manufacturers. Overall, both titres and ACE2 binding inhibition peaked approximately 28 days post-second vaccination and then decreased., Competing Interests: NS-M was a speaker at Luminex user meetings in the past. The Natural and Medical Sciences Institute at the University of Tübingen is involved in applied research projects as a fee for services with the Luminex Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dulovic, Kessel, Harries, Becker, Ortmann, Griesbaum, Jüngling, Junker, Hernandez, Gornyk, Glöckner, Melhorn, Castell, Heise, Kemmling, Tonn, Frank, Illig, Klopp, Warikoo, Rath, Suckel, Marzian, Grupe, Kaiser, Traenkle, Rothbauer, Kerrinnes, Krause, Lange, Schneiderhan-Marra and Strengert.)

Background: Until now, information on the spread of SARS-CoV-2 infections in Germany has been based mainly on data from the public health offices. It may be assumed that these data do not include many cases of asymptomatic and mild infection., Methods: We determined seroprevalence over the course of the pandemic in a sequential, multilocal seroprevalence study (MuSPAD). Study participants were recruited at random in seven administrative districts (Kreise) in Germany from July 2020 onward; each participant was tested at two different times 3-5 months apart. Test findings on blood samples were used to determine the missed-case rate of reported infections, the infection fatality rate (IFR), and the association between seropositivity and demographic, socio-economic, and health-related factors, as well as to evaluate the self-reported results of PCR and antigenic tests. The registration number of this study is DRKS00022335., Results: Among non-vaccinated persons, the seroprevalence from July to December 2020 was 1.3-2.8% and rose between February and May 2021 to 4.1-13.1%. In July 2021, 35% of tested persons in Chemnitz were not vaccinated, and the seroprevalence among these persons was 32.4% (07/2021). The surveillance detection ratio (SDR), i.e., the ratio between the true number of infections estimated from seroprevalence and the actual number or reported infections, varied among the districts included in the study from 2.2 to 5.1 up to December 2020 and from 1.3 to 2.9 up to June 2021, and subsequently declined. The IFR was in the range of 0.8% to 2.4% in all regions except Magdeburg, where a value of 0.3% was calculated for November 2020. A lower educational level was associated with a higher seropositivity rate, smoking with a lower seropositivity rate. On average, 1 person was infected for every 8.5 persons in quarantine., Conclusion: Seroprevalence was low after the first wave of the pandemic but rose markedly during the second and third waves. The missed-case rate trended downward over the course of the pandemic.

To investigate factors associated with time in physical activity intensities, we assessed physical activity of 249 men and women (mean age 51.3 years) by 7-day 24h-accelerometry (ActiGraph GT3X+). Triaxial vector magnitude counts/minute were extracted to determine time in inactivity, in low-intensity, moderate, and vigorous-to-very-vigorous activity. Cross-sectional associations with sex, age, body mass index, waist circumference, smoking, alcohol consumption, education, employment, income, marital status, diabetes, and dyslipidaemia were investigated in multivariable regression analyses. Higher age was associated with more time in low-intensity (mean difference, 7.3 min/d per 5 years; 95% confidence interval 2.0,12.7) and less time in vigorous-to-very-vigorous activity (-0.8 min/d; -1.4, -0.2), while higher BMI was related to less time in low-intensity activity (-3.7 min/d; -6.3, -1.2). Current versus never smoking was associated with more time in low-intensity (29.2 min/d; 7.5, 50.9) and less time in vigorous-to-very-vigorous activity (-3.9 min/d; -6.3, -1.5). Finally, having versus not having a university entrance qualification and being not versus full time employed were associated with more inactivity time (35.9 min/d; 13.0, 58.8, and 66.2 min/d; 34.7, 97.7, respectively) and less time in low-intensity activity (-31.7 min/d; -49.9, -13.4, and -50.7; -76.6, -24.8, respectively). The assessed factors show distinct associations with activity intensities, providing targets for public health measures aiming to increase activity.

Background: We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders., Methods: We used data and blood samples from the pretest phases of the German National Cohort, obtained from six of the 18 study centers (n = 1199). All centers applied standardized instruments including face-to-face interviews, anthropometric measurements and collection of blood samples. Self-reported histories of diabetes mellitus, heart attack and elevated blood cholesterol and/or lipids were recorded. Height, weight and blood pressure were measured. ANAs were detected using a semi-automated system (AKLIDES®; Medipan GmbH, Dahlewitz, Germany). A positive ANA was defined as a titer ≥ 1:80. ANA were classified as weakly (1:80 or 1:160), moderately (1:320 or 1:640) or strongly (≥1:1280) positive. Specific autoantibodies against nuclear antigens were detected with second-step assays according to the ANA staining pattern. Associations between the assessed disorders and ANA positivity and pattern were examined using sex and age-adjusted mixed-effects logistic regression models., Results: Thirty-three percent (95% confidence interval; 31-36%) of the 1196 participants (measurements could not be obtained from three samples) were ANA positive (titer ≥ 1:80). The proportions of weakly, moderately and strongly positive ANA were 29%, 3.3% and 1.3%, respectively. ANA positivity was more common among women than men across all titers (χ 2 , p = 0.03). ANA positivity, even when stratified according to height of titer or immunofluorescent pattern, was not associated with diabetes, elevated blood cholesterol and/or lipids, obesity or hypertension. Second-step autoantibody assays were positive in 41 of the 83 samples (49%) tested, with anti-DFS70 (n = 13) and anti-dsDNA (n = 7) being most frequent. These subgroups were too small to test for associations with the disorders assessed., Conclusions: The prevalence of ANA positivity in the German general population was similar to values reported from other countries. Contrary to other studies, there was no association with selected self-reported and objectively measured cardiovascular and metabolic variables.

Introduction: Whole-body magnetic resonance (MR) imaging is increasingly implemented in population-based cohorts and clinical settings. However, to quantify the variability introduced by the different scanners is essential to make conclusions about clinical and biological data, and relevant for internal/external validity. Thus, we determined the interscanner and intrascanner variability of different 3 T MR scanners for whole-body imaging., Methods: Thirty volunteers were enrolled to undergo multicentric, interscanner as well intrascanner imaging as part of the German National Cohort pilot studies. A comprehensive whole-body MR protocol was installed at 9 sites including 7 different MR scanner models by all 4 major vendors. A set of quantitative, organ-specific measures (n = 20; eg, volume of brain's gray/white matter, pulmonary trunk diameter, vertebral body height) were obtained in blinded fashion. Reproducibility was determined using mean weighted relative differences and intraclass correlation coefficients., Results: All participants (44 ± 14 years, 50% female) successfully completed the imaging protocol except for two because of technical issues. Mean scan time was 2 hours and 32 minutes and differed significantly across scanners (range, 1 hour 59 minutes to 3 hours 12 minutes). A higher reproducibility of obtained measurements was observed for intrascanner than for interscanner comparisons (intraclass correlation coefficients, 0.80 ± 0.17 vs 0.60 ± 0.31, P = 0.005, respectively). In the interscanner comparison, mean relative difference ranged from 1.0% to 53.2%. Conversely, in the intrascanner comparison, mean relative difference ranged from 0.1% to 15.6%. There were no statistical differences for intrascanner and interscanner reproducibility between the different organ foci (all P ≥ 0.24)., Conclusions: While whole-body MR imaging-derived, organ-specific parameters are generally associated with good to excellent reproducibility, smaller differences are obtained when using identical MR scanner models by a single vendor.

Objectives: We compared participation and compliance with a web-based data collection on infections among population-based samples recruited in different ways., Methods: Individuals were recruited from participants in the German National Cohort study (Group A, n = 279) or persons who were invited to this study but did not participate (Group B, n = 53). A third group was invited to the web-based study only (Group C, n = 145)., Results: Response varied among groups between 3 % (B), 11 % (C) and 61 % (A), but compliance was similar (81-85 %). Response did not differ by age and sex. Compliance was lower among the youngest and oldest participants. In addition, participants currently not employed were more likely to have better compliance. Semi-parametric group-based modelling identified three distinct compliance trajectories; "poor compliance" (8 %), "improving compliance" (14 %) and "very good compliance" (78 %)., Conclusions: Participation differed among modes of recruitment, but compliance was similar among groups and notably high. Different recruitment approaches can be used and collected data can be combined to achieve greater sample sizes for longitudinal web-based studies.

Objectives: In this pilot study within the Pretest 2 phase of the German National Cohort, we aimed to (1) test the hypothesis that distance and duration of travel to a study centre may affect participation rates and participants' satisfaction and (2) to obtain data that would help to select recruitment areas around the study centre Hannover with the greatest projected participation rate for the main study., Setting: Mixed urban/suburban environment in Northern Germany with approximately 600,000 inhabitants. 4 recruitment areas with divergent estimated mean distances (range, 7-40 km) and duration of travel to the study centre Hannover were selected., Participants: 1050 men and women (ratio, 1:1), aged 20-69 years, were randomly selected from the population registries of the 4 recruitment areas and invited by mail to participate in the Pretest 2 study programme at the study centre Hannover, covering a variety of questionnaire-based and physical assessments. 166 individuals participated (16%)., Interventions: All 166 participants completed a travel questionnaire containing 5 items relating to travel duration and satisfaction, amounting to a participation rate of 100% in the questionnaire-based part of the study., Results: Participation rates in the Pretest 2 programme at the study centre Hannover by area ranged from 11% (area farthest from the study centre, estimated median distance 38 km) to 18% (nearest area, 2 km). The odds of non-participation were highest in the area farthest from the study centre (adjusted OR 2.06; p=0.01; CI 1.28 to 3.32). Nonetheless, 97% of participants were satisfied with travel duration., Conclusions: Increasing distance was associated with a lower participation rate. However, acceptance of duration of travel was high, irrespective of distance or duration. Thus, recruiting in farther away locations may select individuals with a greater frustration tolerance for travel to the study centre, perhaps due to a greater interest in participating in health-oriented studies and thus different health-related behaviour., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Biochemical markers of brain damage, e.g. ischemic stroke, should reflect the volume of irreversibly damaged brain parenchyma and the clinical outcome in a single patient in order to allow estimation of prognosis at an early stage. Tau protein, which derives predominantly from neurons and axons, is elevated in the cerebrospinal fluid of patients with neurodegenerative disease. This makes tau protein a potential marker of neuronal/axonal injury. In order to test this hypothesis, the current study aimed at showing that tau protein is measurable in the blood after acute ischemic stroke and that it correlates with clinical disability and stroke volume. In a longitudinal prospective study we measured tau protein serum levels with an ELISA in 30 patients longitudinally after ischemic stroke. Tau protein was detectable within 5 days after ischemia in the sera of 7/20 patients with MRI-proven infarction and in 2/10 patients with transitory ischemic attack; both of them had a small infarction visible on the MRI scan. Tau protein was measurable within 6 h after symptom onset, peaked after 3-5 days and correlated with infarct volume and disability after 3 months. In conclusion, serum tau protein is a candidate marker of axonal injury. In stroke, its clinical use is limited, because it is detectable only in a proportion of patients., (Copyright 2002 S. Karger AG, Basel)