BACKGROUND:There is a growing consensus that screening for subclinical preheart failure (HF) may reduce the burden of symptomatic HF by allowing for timely preventive interventions. However, validated screening algorithms are currently lacking. The aim of this study was to evaluate a fully mobile telemedically supervised cardiac magnetic resonance, as a simple standardized, and ubiquitously applicable screening algorithm for subclinical pre-HF in rural and underresourced regions. METHODS:HERZCHECK was a cross-sectional cohort study conducted at 12 sites across rural and underresourced regions of Germany. Asymptomatic participants (40-69 years) with ≥1 cardiovascular risk factor-obesity, smoking, arterial hypertension, diabetes, hypercholesterolemia, or chronic kidney disease-were enrolled and underwent telemedically supervised contrast-free short cardiac magnetic resonance in mobile screening units. Subclinical pre-HF was diagnosed using a predefined cutoff of global longitudinal strain ≥-15%. A matched and entropy-balanced control cohort constructed from claims data was used to determine the time difference between detection of subclinical pre-HF in HERZCHECK and the first symptom-based diagnosis of HF within the standard of care. RESULTS:Between June 2021 and April 2023, 4666 participants were enrolled in the study, of which 4509 participants were included in the final analysis. The prevalence of subclinical pre-HF in the studied at-risk population was 22.7% (95% CI, 21.5%-23.9%). Global longitudinal strain-based screening identified subclinical pre-HF 6.7 years before the average onset of symptomatic HF within the standard of care (n=8420). CONCLUSIONS:Subclinical pre-HF affects approximately one-fourth of the at-risk population in rural and underresourced regions. The HERZCHECK approach identifies patients suitable for targeted preventive interventions ≈7 years earlier than the standard of care. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05122793.

Purpose Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. Methods The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. Results As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. Conclusion NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. Trial registration Registered at the German registry for clinical studies (DRKS00023742).

Chronic pain (CP) is a public health problem with significant consequences for the patient's life. This study aims to analyze the prevalence of sick leave due to CP in Spain and to explore how pain intensity and mental disorders mediate the relationship between sick leave and health-related quality of life (HRQL) in subjects with CP. This study is a secondary analysis from data collected in a cross-sectional study called "Barometro del Dolor" with 7058 participants, representing the Spanish adult population. Sociodemographic information, presence and characteristics of CP, sick leave due to CP, anxiety and depression (HADS) and HRQL (SF-12v2) were collected. The prevalence of sick leave and four serial multiple mediation analyses were conducted. CP prevalence was 25.9% (95%CI 24.8-26.9), while 28.6% (95%CI 26.4-30.8) needed sick leave due to CP in the last year. Sick leave was associated with worse HRQL through the mediating effect of pain intensity and anxiety/depression, showing a non-significant direct effect for the mental component summary of the SF12v2 after accounting for the indirect effects. The direct effects linked CP sick leave to a worse physical component summary, higher pain intensity, anxiety and depression. This study highlights the strong impact of CP on the Spanish workforce providing new insights into hypothesized statistical pathways linking CP sick leave and HRQL through pain intensity and anxiety/depression symptoms.

Background and aims Heart failure (HF) is an imminent global health problem. Yet established screening algorithms for asymptomatic pre-HF, allowing for early and effective preventive interventions, are largely lacking. The HERZCHECK trial, conducted in structurally underserved rural regions of North-Eastern Germany, aims to close this gap by evaluating the feasibility, diagnostic efficacy, and cost-effectiveness of a fully mobile, telemedically-supervised screening approach, combining cardiac magnetic resonance imaging (CMR) and laboratory testing as central elements. Study Design and Methodology The HERZCHECK trial is a prospective, randomized controlled trial employing a PROBE (prospective randomized open, blinded endpoint) design. The study targets asymptomatic adults aged 40-69 years without a history of HF, but with at least one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, obesity, smoking/tobacco consumption, chronic diabetes mellitus, or chronic kidney disease. Participants undergo a comprehensive screening examination including a questionnaire-based medical history, laboratory testing, and CMR at baseline. Based on CMR-derived global longitudinal strain (GLS), participants are classified as stratum A (GLS < -15%), B (GLS ≥ -15% to < -11%), or C (GLS ≥ -11%), with strata B and C being defined as asymptomatic pre-HF. 10% of participants in stratum A and all of stratum B and C are subsequently randomized into two groups, receiving either conventional or innovative medical reports, the latter including information on GLS, guideline-based recommendations, and access to a life-style intervention app for cardiovascular prevention. Additionally, treating physicians of participants in the innovative group are granted access to an expert center for telemedical enquires. Follow-up assessments are performed over 12 months to evaluate changes in GLS, as well as adverse cardiac events and quality of life. Conclusion HERZCHECK aims to provide a blueprint for a comprehensive, contemporary screening approach tailored to the needs of the targeted structurally underserved population. By implementing this approach in a representative at-risk cohort, HERZCHECK will provide important new information about (a) the prevalence of asymptomatic pre-HF in at-risk patients and (b) the feasibility, added diagnostic value and health economic aspects of CMR exams as part of future screening mechanisms for HF in clinical routine care. (NCT05122793)

BACKGROUND AND AIMS:Heart failure (HF) is an imminent global health problem. Yet established screening algorithms for asymptomatic pre-HF, allowing for early and effective preventive interventions, are largely lacking. The HERZCHECK trial, conducted in structurally underserved rural regions of North-Eastern Germany, aims to close this gap by evaluating the feasibility, diagnostic efficacy, and cost-effectiveness of a fully mobile, telemedically-supervised screening approach, combining cardiovascular magnetic resonance (CMR) imaging and laboratory testing as central elements. STUDY DESIGN AND METHODOLOGY:The HERZCHECK trial is a prospective, randomized controlled trial employing a prospective randomized open blinded endpoint design. The study targets asymptomatic adults aged 40-69 years without a history of HF, but with at least one of the following cardiovascular risk factors: hypertension, hypercholesterolemia, obesity, smoking/tobacco consumption, chronic diabetes mellitus, or chronic kidney disease. Participants undergo a comprehensive screening examination including a questionnaire-based medical history, laboratory testing, and CMR at baseline. Based on CMR-derived global longitudinal strain (GLS), participants are classified as stratum A (GLS < -15%), B (GLS ≥ -15% to < -11%), or C (GLS ≥ -11%), with strata B and C being defined as asymptomatic pre-HF. Ten percent of participants in stratum A and all of stratum B and C are subsequently randomized into two groups, receiving either conventional or innovative medical reports, the latter including information on GLS, guideline-based recommendations, and access to a lifestyle intervention app for cardiovascular prevention. Additionally, treating physicians of participants in the innovative group are granted access to an expert center for telemedical inquiries. Follow-up assessments are performed over 12 months to evaluate changes in GLS, as well as adverse cardiac events and quality of life. CONCLUSION:HERZCHECK aims to provide a blueprint for a comprehensive, contemporary screening approach tailored to the needs of the targeted structurally underserved population. By implementing this approach in a representative at-risk cohort, HERZCHECK will provide important new information about (a) the prevalence of asymptomatic pre-HF in at-risk patients and (b) the feasibility, added diagnostic value and health economic aspects of CMR exams as part of future screening mechanisms for HF in clinical routine care (NCT05122793).

Introduction Breast cancer is the most common form of cancer in women. A considerable number of women with breast cancer who have been treated with chemotherapy subsequently develop neurological symptoms such as concentration and memory difficulties (also known as ‘chemobrain’). Currently, there are no validated therapeutic approaches available to treat these symptoms. Cognitive training holds the potential to counteract cognitive impairment. Combining cognitive training with concurrent transcranial direct current stimulation (tDCS) could enhance and maintain the effects of this training, potentially providing a new approach to treat post-chemotherapy subjective cognitive impairment (PCSCI). With this study, we aim to investigate the effects of multi-session tDCS over the left dorsolateral prefrontal cortex in combination with cognitive training on cognition and quality of life in women with PCSCI.Methods and analysis The Neuromod-PCSCI trial is a monocentric, randomised, double-blind, placebo-controlled study. Fifty-two women with PCSCI after breast cancer therapy will receive a 3-week tDCS-assisted cognitive training with anodal tDCS over the left dorsolateral prefrontal cortex (target intervention), compared with cognitive training plus sham tDCS (control intervention). Cognitive training will consist of a letter updating task. Primary outcome will be the performance in an untrained task (n-back task) after training. In addition, feasibility, safety and tolerability, as well as quality of life and performance in additional untrained tasks will be investigated. A follow-up visit will be performed 1 month after intervention to assess possible long-term effects. In an exploratory approach, structural and functional MRI will be acquired before the intervention and at post-intervention to identify possible neural predictors for successful intervention.Ethics and dissemination Ethical approval was granted by the ethics committee of the University Medicine Greifswald (BB236/20). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.Trial registration number ClinicalTrials.gov; NCT04817566, registered on 26 March 2021.

Long-term changes in health-related quality of life (HrQoL) after SARS-CoV-2 infection are common, but their causes and consequences are poorly understood. This prospective, population-based study examined associations between HrQoL and 49 demographic and clinical variables. HrQoL was assessed using the European Quality-of-Life-5-Dimensions-5-Level-Version in 3,475 participants (56% female; aged 18–88 years) approximately 9 months (baseline) and 26 months (follow-up) after their initial infection. Results were compared with the demographic and clinical variables using recursive feature elimination and random forest regression analyses. A statistically significant improvement in HrQoL was observed during the observation period. At baseline, 39% of the variance in HrQoL was explained by fatigue, muscle pain, number of remaining symptoms (RS), perceived stress, and age. At follow-up, fatigue, RS, perceived stress, muscle and joint pain, and age explained 54% of the variance in HrQoL. Changes in HrQoL were associated with changes in fatigue, RS, and perceived stress, meaning that if these decreased from baseline to follow-up, then HrQoL was improved. However, it was not possible to predict whether an individual’s HrQoL would improve or worsen 1 year later based on baseline variable scores. The aforementioned symptoms are specifically associated with impairment in the population’s usual activities.

The patient voice is critical to achieving value-based care, improving health outcomes, and advancing medical research. However, a key challenge is how to translate this "voice" into scientifically valid data that can inform evidence-based clinical decisions. One of the biggest barriers is the sheer variety of available patient-reported outcomes (PROs) and patient-reported outcome measures (PROMs) and the associated challenges of translation, validation, implementation, and interpretation, making it difficult to obtain valid and comparable health outcomes. The authors present a harmonized global approach to international standardization of PROs and PROMs. This approach has the potential to accelerate patient-centered care by facilitating the collection of accurate and comparable real-world evidence on health outcomes that matter most to patients. This proposed approach consists of two elements: a data collection process based on a common set of PROs and a state-of-the-art measurement approach based on item response theory. First, there is growing evidence that outcomes such as pain, fatigue, anxiety, depression, sleep disturbance, physical function, and the ability to participate in social roles and activities are relevant for most people, irrespective of their health condition. Measuring these outcomes routinely in all patients could increase outcome comparability and utility for a range of stakeholders. Second, a measurement strategy based on a state-of-the-art psychometric approach — using item response theory (IRT)-based item banks — offers short, flexible, sustainable, and universally applicable PROMs with robust measurement properties and a common measurement scale. The unique integration of these two elements offers the potential to collect comparable PROM data across patients and providers to support shared decision-making, which may lead to better outcomes. The Patient-Reported Outcomes Measurement Information System (PROMIS) is a globally used example of such an approach. The PROMIS Profile measures serve as a resource for measuring a harmonized core set of PROs across medical conditions, languages, and countries. To meet the United Nations Sustainable Development Goal of ensuring healthy lives and promoting well-being for all, at all ages, a collaborative effort is needed to achieve consensus on international standardization of PROs and PROMs to accelerate patient-centered care across health conditions, settings, and countries. The authors propose to routinely measure a core set of broadly relevant PROs in all patients, regardless of their health condition, with universally applicable IRT-based PROMs.

Abstract Background Health-related quality of life (HRQL) has become an important outcome parameter in cardiology. The MOS 36-ltem Short-Form Health Survey (SF-36) and the PROMIS-29 are two widely used generic measures providing composite HRQL scores. The domains of the SF-36, a well-established instrument utilized for several decades, can be aggregated to physical (PCS) and mental (MCS) component summary scores. Alternative scoring algorithms for correlated component scores (PCSc and MCSc) have also been suggested. The PROMIS-29 is a newer but increasingly used HRQL measure. Analogous to the SF-36, physical and mental health summary scores can be derived from PROMIS-29 domain scores, based on a correlated factor solution. So far, scores from the PROMIS-29 are not directly comparable to SF-36 results, complicating the aggregation of research findings. Thus, our aim was to provide algorithms to convert PROMIS-29 data to well-established SF-36 component summary scores. Methods Data from n = 662 participants of the Berlin Long-term Observation of Vascular Events (BeLOVE) study were used to estimate linear regression models with either PROMIS-29 domain scores or aggregated PROMIS-29 physical/mental health summary scores as predictors and SF-36 physical/mental component summary scores as outcomes. Data from a subsequent assessment point (n = 259) were used to evaluate the agreement between empirical and predicted SF-36 scores. Results PROMIS-29 domain scores as well as PROMIS-29 health summary scores showed high predictive value for PCS, PCSc, and MCSc (R2 ≥ 70%), and moderate predictive value for MCS (R2 = 57% and R2 = 40%, respectively). After applying the regression coefficients to new data, empirical and predicted SF-36 component summary scores were highly correlated (r > 0.8) for most models. Mean differences between empirical and predicted scores were negligible (|SMD|<0.1). Conclusions This study provides easy-to-apply algorithms to convert PROMIS-29 data to well-established SF-36 physical and mental component summary scores in a cardiovascular population. Applied to new data, the agreement between empirical and predicted SF-36 scores was high. However, for SF-36 mental component summary scores, considerably better predictions were found under the correlated (MCSc) than under the original factor model (MCS). Additionally, as a pertinent byproduct, our study confirmed construct validity of the relatively new PROMIS-29 health summary scores in cardiology patients.

BackgroundDespite the high prevalence and major disability associated with fatigue and cognitive deficits after SARS-CoV-2 infection, little is known about long-term trajectories of these sequelae. We aimed to assess long-term trajectories of these conditions and to identify risk factors for non-recovery.MethodsWe analyzed longitudinal data from the population-based COVIDOM/NAPKON-POP cohort in Germany. Participants with confirmed SARS-CoV-2 infection were assessed at least 6 months (baseline) and again at least 18 months (follow-up) after infection using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale (cutoff ≤ 30) and the Montreal Cognitive Assessment (MoCA, cutoff ≤ 25). Predictors of recovery from fatigue or cognitive deficits between assessments were identified through univariate and multivariable logistic regression models. The COVIDOM study is registered at the German registry for clinical studies (DRKS00023742) and at ClinicalTrials.gov (NCT04679584).FindingsBetween 15 November 2020 and 9 May 2023, a total of 3038 participants were assessed at baseline (median 9 months after infection) and 83% responded to invitations for follow-up (median 26 months after infection). At baseline, 21% (95% confidence interval (CI) [20%, 23%]) had fatigue and 23% (95% CI [22%, 25%]) had cognitive deficits according to cutoff scores on the FACIT-Fatigue or MoCA. Participants with clinically relevant fatigue (at baseline) showed significant improvement in fatigue scores at follow-up (Hedges’ g [95% CI] = 0.73 [0.60, 0.87]) and 46% (95% CI [41%, 50%]) had recovered from fatigue. Participants with cognitive deficits showed a significant improvement in cognitive scores (g [95% CI] = 1.12 [0.90, 1.33]) and 57% (95% CI [50%, 64%]) had recovered from cognitive deficits. Patients with fatigue exhibiting a higher depressive symptom burden and/or headache at baseline were significantly less likely to recover. Significant risk factors for cognitive non-recovery were male sex, older age and <12 years of school education. Importantly, SARS-CoV-2 reinfection had no significant impact on recovery from fatigue or cognitive deficits.InterpretationFatigue and cognitive deficits are common sequelae after SARS-CoV-2 infection. These syndromes improved over time and about half of the patients recovered within two years. The identified risk factors for non-recovery from fatigue and cognitive deficits could play an important role in shaping targeted strategies for treatment and prevention.FundingFunded by the German Federal Ministry of Education and Research (BMBF; grant number 01KX2121) and German Research Foundation (DFG) Excellence Cluster “Position Medicine in Information”.

In patients presenting with low back pain (LBP), once specific causes are excluded (fracture, infection, inflammatory arthritis, cancer, cauda equina and radiculopathy) many clinicians pose a diagnosis of non-specific LBP. Accordingly, current management of non-specific LBP is generic. There is a need for a classification of non-specific LBP that is both data- and evidence-based assessing multi-dimensional pain-related factors in a large sample size. The “PRedictive Evidence Driven Intelligent Classification Tool for Low Back Pain” (PREDICT-LBP) project is a prospective cross-sectional study which will compare 300 women and men with non-specific LBP (aged 18–55 years) with 100 matched referents without a history of LBP. Participants will be recruited from the general public and local medical facilities. Data will be collected on spinal tissue (intervertebral disc composition and morphology, vertebral fat fraction and paraspinal muscle size and composition via magnetic resonance imaging [MRI]), central nervous system adaptation (pain thresholds, temporal summation of pain, brain resting state functional connectivity, structural connectivity and regional volumes via MRI), psychosocial factors (e.g. depression, anxiety) and other musculoskeletal pain symptoms. Dimensionality reduction, cluster validation and fuzzy c-means clustering methods, classification models, and relevant sensitivity analyses, will classify non-specific LBP patients into sub-groups. This project represents a first personalised diagnostic approach to non-specific LBP, with potential for widespread uptake in clinical practice. This project will provide evidence to support clinical trials assessing specific treatments approaches for potential subgroups of patients with non-specific LBP. The classification tool may lead to better patient outcomes and reduction in economic costs.

Background The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). Methods NAPKON-HAP is a multi‐centered prospective observational study with a long‐term follow‐up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. Results Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. Conclusion NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.

Study Design. Prospective quasi-experimental observational study. Objective. The objective of this study was to evaluate whether duration of surgery is a modifiable risk factor for postoperative delirium (POD) after spine surgery and explore further modifiable risk factors. In addition, we sought to investigate the association between POD and postoperative cognitive dysfunction and persistent neurocognitive disorders. Summary of Background Data. Advances in spine surgery enable technically safe interventions in elderly patients with disabling spine disease. The occurrence of POD and delayed neurocognitive complications (e.g. postoperative cognitive dysfunction/persistent neurocognitive disorder) remain a concern since these contribute to inferior functional outcomes and long-term care dependency after spine surgery. Materials and Methods. This prospective single-center study recruited patients aged 60 years or above and scheduled for elective spine surgery between February 2018 and March 2020. Functional (Barthel Index, BI) and cognitive outcomes [Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test battery; telephone Montréal Cognitive Assessment] were assessed at baseline, three (V3), and 12 months postoperatively. The primary hypothesis was that the duration of surgery predicts POD. Multivariable predictive models of POD included surgical and anesthesiological parameters. Results. Twenty-two percent of patients developed POD (n=22/99). In a multivariable model, duration of surgery [ORadj=1.61/h (95% CI, 1.20–2.30)], age [ORadj=1.22/yr (95% CI, 1.10–1.36)], and baseline deviations of intraoperative systolic blood pressure [25th percentile: ORadj=0.94/mm Hg (95% CI, 0.89–0.99); 90th percentile: ORadj=1.07/mm Hg (95% CI, 1.01–1.14)] were significantly associated with POD. Postoperative cognitive scores generally improved (V3, ΔCERAD total z-score: 0.22±0.63). However, this positive group effect was counteracted by POD [beta: −0.87 (95% CI, −1.31 to 0.42)], older age [beta: −0.03/yr (95% CI, −0.05 to 0.01)], and lack of functional improvement [ΔBI; beta: −0.04/point (95% CI, −0.06 to 0.02)]. Cognitive scores at twelve months remained inferior in the POD group, adjusted for baseline cognition/age. Conclusions. This study identified distinct neurocognitive effects after spine surgery, which are influenced by perioperative risk factors. Potential cognitive benefits are counteracted by POD, rendering its prevention critical in an aging population.

Background Most of the previous studies on health sequelae of COVID-19 are uncontrolled cohorts and include a relatively short follow-up. This population-based multi-center cohort study examined health consequences among individuals about 1 to 1.5 years after SARS-CoV-2 infection compared with non-infected. Methods The study population consisted of adults (≥ 18 years) from four municipalities particularly affected by the COVID-19 pandemic in the year 2020 who completed a detailed follow-up questionnaire on health-related topics. Exposure was the SARS-CoV-2 infection status (based on IgG antibodies, PCR test, or physician-diagnosis of COVID-19) at baseline (May to December 2020). Outcomes assessed at follow-up (October 2021 to January 2022; mean: 452 days) included recurrent or persistent health complaints, incident diseases, health-related quality of life (PROMIS-29), subjective health, and subjective memory impairment. Logistic and linear regression models were adjusted for baseline sociodemographic and lifestyle characteristics (age, sex, municipality, education, smoking, body mass index), pre-existing health conditions (chronic disease/health problem, health-related activity limitation, depressive/anxiety disorder), and follow-up time. Results Among 4817 participants, 350 had a SARS-CoV-2 infection at baseline and 4467 had no infection at baseline or during follow-up. Those with an infection statistically significantly more often reported 7 out of 18 recurrent or persistent health complaints at follow-up: smell/taste disorders (12.8% vs. 3.4%, OR 4.11), shortness of breath (23.0% vs. 9.5%, 3.46), pain when breathing (4.7% vs. 1.9%, 2.36), fatigue (36.9% vs. 26.1%, 1.76), weakness in legs (12.8% vs. 7.8%, 1.93), myalgia/joint pain (21.9% vs. 15.1%, 1.53) and cough (30.8% vs. 24.8%, 1.34) and 3 out of 6 groups of incident diseases: liver/kidney (2.7% vs. 0.9%, 3.70), lung (3.2% vs. 1.1%, 3.50) and cardiovascular/metabolic (6.5% vs. 4.0%, 1.68) diseases. Those with an infection were significantly more likely to report poor subjective health (19.3% vs. 13.0%, 1.91), memory impairment (25.7% vs. 14.3%, 2.27), and worse mean scores on fatigue and physical function domains of PROMIS-29 than non-infected. Conclusion Even after more than one year, individuals with SARS-CoV-2 infection showed an increased risk of various health complaints, functional limitations, and worse subjective well-being, pointing toward profound health consequences of SARS-CoV-2 infection relevant for public health.

Introduction The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations. Methods and analysis A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after ~90 days and includes assessments of the patient’s medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including ‘OMICs’ technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes. Ethics and dissemination The study was approved by the Charité—Universitätsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations. Study registration First study phase: Approved WHO primary register: German Clinical Trials Register: https://drks.de/search/de/trial/DRKS00016852 ; WHO International Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016852 . Recruitment started on July 18, 2017. Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/ DRKS00023323. Recruitment started on January 1, 2021.

Background: Reliable estimates of frequency, severity and associated factors of both fatigue and cognitive impairment after COVID-19 are needed. Also, it is not clear whether the two are distinct sequelae of COVID-19 or part of the same syndrome. Methods: In this prospective multicenter study, frequency of post-COVID fatigue and cognitive impairment were assessed in 969 patients ≥6 months after SARS-CoV-2 infection with the FACIT-Fatigue scale (cutoff ≤30) and Montreal Cognitive Assessment (≤25 mild, ≤17 moderate impairment). 969 matched non-COVID controls were drawn from a randomized, Germany-wide population survey. Associated sociodemographic, comorbid, clinical, psychosocial factors and laboratory markers were identified with univariate and multivariable linear regression models. Outcomes: On average 9 months after infection, 19% of patients had clinically relevant fatigue, compared to 8% of matched non-COVID controls (p<0.001). Factors associated with post-COVID fatigue were female gender, younger age, history of depression and the number of acute COVID symptoms. Among acute COVID symptoms, altered consciousness, dizziness and myalgia were most strongly associated with long-term fatigue. Moreover, 26% of patients had mild and 1% had moderate cognitive impairment. Factors associated with cognitive impairment were older age, male gender, shorter education and a history of neuropsychiatric disease. There was no significant correlation between fatigue and cognitive impairment and only 5% of patients suffered from both conditions. Interpretation: Fatigue and cognitive impairment are two common, but distinct sequelae of COVID-19 with potentially separate pathophysiological pathways.Trial Registration: The COVIDOM study is registered at the German registry for clinical studies (DRKS00023742) and at ClinicalTrials.gov (NCT04679584).Funding: The study was funded by the German Federal Ministry of Education and Research(BMBF).Declaration of Interest: KGH reports speaker’s honoraria, consulting fees, lecture honoraria and/or study grants from Abbott, Amarin, AstraZeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Medronic, Pfizer, Portola, Premier Research, Sanofi, SUN Pharma, and W.L. Gore and Associates, all of which were unrelated to this work. ME reports grants from Bayer and fees paid to the Charité from Abbot, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, GSK, Sanofi, Covidien, Novartis and Pfizer, all of which were unrelated to this work. The other authors have reported no potential conflicts of interest.Ethical Approval: All patients and healthy control participants provided written informed consent to the respective studies. Both studies were approved by the local ethics committees at respective study centers.

The domains of the MOS 36-ltem Short-Form Health Survey (SF-36) can be aggregated to physical (PCS) and mental (MCS) component summary scores, which are widely used measures of patient-reported health. PCS and MCS were originally derived using an uncorrelated factor model, potentially leading to problems with interpretation of results. Consequently, modified scoring algorithms for correlated SF-36 summary scores (PCSc and MCSc) have been suggested. The PROMIS-29 v2.0 is a newer generic health measure which is increasingly used as an alternative to the SF-36. PROMIS-29 physical and mental summary scores can be derived from individual PROMIS-29 domains. The objective of this study was to establish algorithms to predict SF-36 component summary scores from PROMIS-29 scores.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON’s goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36–62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON’s design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities. Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584

Introduction A substantial number of patients diagnosed with COVID-19 experience long-term persistent symptoms. First evidence suggests that long-term symptoms develop largely independently of disease severity and include, among others, cognitive impairment. For these symptoms, there are currently no validated therapeutic approaches available. Cognitive training interventions are a promising approach to counteract cognitive impairment. Combining training with concurrent transcranial direct current stimulation (tDCS) may further increase and sustain behavioural training effects. Here, we aim to examine the effects of cognitive training alone or in combination with tDCS on cognitive performance, quality of life and mental health in patients with post-COVID-19 subjective or objective cognitive impairments. Methods and analysis This study protocol describes a prospective randomised open endpoint-blinded trial. Patients with post-COVID-19 cognitive impairment will either participate in a 3-week cognitive training or in a defined muscle relaxation training (open-label interventions). Irrespective of their primary intervention, half of the cognitive training group will additionally receive anodal tDCS, all other patients will receive sham tDCS (double-blinded, secondary intervention). The primary outcome will be improvement of working memory performance, operationalised by an n-back task, at the postintervention assessment. Secondary outcomes will include performance on trained and untrained tasks and measures of health-related quality of life at postassessment and follow-up assessments (1 month after the end of the trainings). Ethics and dissemination Ethical approval was granted by the Ethics Committee of the University Medicine Greifswald (number: BB 066/21). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences. Trial registration number NCT04944147 .