Targeted metabolomics identifies accurate CSF metabolite biomarkers for the differentiation between COVID-19 with neurological involvement and CNS infections with neurotropic viral pathogens.

BACKGROUND: COVID-19 is primarily considered a respiratory tract infection, but it can also affect the central nervous system (CNS), which can result in long-term sequelae. In contrast to CNS infections by classic neurotropic viruses, SARS-CoV-2 is usually not detected in cerebrospinal fluid (CSF) from patients with COVID-19 with neurological involvement (neuro-COVID), suggesting fundamental differences in pathogenesis. METHODS: To assess differences in CNS metabolism in neuro-COVID compared to CNS infections with classic neurotropic viruses, we applied a targeted metabolomic analysis of 630 metabolites to CSF from patients with (i) COVID-19 with neurological involvement [n = 16, comprising acute (n = 13) and post-COVID-19 (n = 3)], (ii) viral meningitis, encephalitis, or myelitis (n = 10) due to herpes simplex virus (n = 2), varicella zoster virus (n = 6), enterovirus (n = 1) and tick-borne encephalitis virus (n = 1), and (iii) aseptic neuroinflammation (meningitis, encephalitis, or myelitis) of unknown etiology (n = 21) as additional disease controls. RESULTS: Standard CSF parameters indicated absent or low neuroinflammation in neuro-COVID. Indeed, CSF cell count was low in neuro-COVID (median 1 cell/µL, range 0-12) and discriminated it accurately from viral CNS infections (AUC = 0.99) and aseptic neuroinflammation (AUC = 0.98). 32 CSF metabolites passed quality assessment and were included in the analysis. Concentrations of differentially abundant (fold change ≥|1.5|, FDR ≤ 0.05) metabolites were both higher (9 and 5 metabolites) and lower (2 metabolites) in neuro-COVID than in the other two groups. Concentrations of citrulline, ceramide (d18:1/18:0), and methionine were most significantly elevated in neuro-COVID. Remarkably, triglyceride TG(20:1_32:3) was much lower (mean fold change = 0.09 and 0.11) in neuro-COVID than in all viral CNS infections and most aseptic neuroinflammation samples, identifying it as highly accurate biomarker with AUC = 1 and 0.93, respectively. Across all samples, TG(20:1_32:3) concentration correlated only moderately with CSF cell count (ρ = 0.65), protein concentration (ρ = 0.64), and Q-albumin (ρ = 0.48), suggesting that its low levels in neuro-COVID CSF are only partially explained by less pronounced neuroinflammation. CONCLUSIONS: The results suggest that CNS metabolite responses in neuro-COVID differ fundamentally from viral CNS infections and aseptic neuroinflammation and may be used to discover accurate diagnostic biomarkers in CSF and to gain insights into differences in pathophysiology between neuro-COVID, viral CNS infections and aseptic neuroinflammation.

Improvement of differential diagnosis of lung cancer by use of multiple protein tumor marker combinations.

BACKGROUND: Differential diagnosis of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in hospitalized patients is crucial for appropriate treatment choice. OBJECTIVE: To investigate the relevance of serum tumor markers (STMs) and their combinations for the differentiation of NSCLC and SCLC subtypes. METHODS: Between 2000 and 2003, 10 established STMs were assessed retrospectively in 311 patients with NSCLC, 128 with SCLC prior systemic first-line therapy and 51 controls with benign lung diseases (BLD), by automatized electrochemiluminescence immunoassay technology. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic efficacy of both individual and multiple STMs with corresponding sensitivities at 90% specificity. Standards for Reporting of Diagnostic Accuracy (STARD guidelines) were followed. RESULTS: CYFRA 21-1 (cytokeratin-19 fragment), CEA (carcinoembryonic antigen) and NSE (neuron specific enolase) were significantly higher in all lung cancers vs BLD, reaching AUCs of 0.81 (95% CI 0.76-0.87), 0.78 (0.73-0.84), and 0.88 (0.84-0.93), respectively. By the three marker combination, the discrimination between benign and all malignant cases was improved resulting in an AUC of 0.93 (95% CI 0.90-0.96). In NSCLC vs. BLD, CYFRA 21-1, CEA and NSE were best discriminative STMs, with AUCs of 0.86 (95% CI 0.81-0.91), 0.80 (0.74-0.85), and 0.85 (0.79-0.91). The three marker combination also improved the AUC: 0.92; 95% CI 0.89-0.96). In SCLC vs. BLD, ProGRP (pro-gastrin-releasing peptide) and NSE were best discriminative STMs, with AUCs of 0.89 (95% CI 0.84-0.94) and 0.96 (0.93-0.98), respectively, and slightly improved AUC of 0.97 (95% CI 0.95-0.99) when in combination. Finally, discrimination between SCLC and NSCLC was possible by ProGRP (AUC 0.86; 95% CI 0.81-0.91), NSE (AUC 0.83; 0.78-0.88) and CYFRA 21-1 (AUC 0.69; 0.64-0.75) and by the combination of the 3 STMs (AUC 0.93; 0.91-0.96), with a sensitivity of 88% at 90% specificity. CONCLUSIONS: The results confirm the power of STM combinations for the differential diagnosis of lung cancer from benign lesions and between histological lung cancer subtypes.

Results of a monocentric field study: value of histology compared to sonication method and conventional tissue culture in the diagnosis of periprosthetic joint infection (PJI).

BACKGROUND: To confirm the diagnosis of periprosthetic joint infection (PJI), the Infectious Diseases Society of America (IDSA) and the International Consensus Meeting (ICM) have defined criteria that include histology as a minor criterion and the sonication method only as an additional criterion. The aim of this monocentric, retrospective study was to investigate the value of histology and whether sonication leads to a more accurate diagnosis. MATERIALS AND METHODS: All revision surgeries for knee and hip arthroplasty between 2017 and 2020 were included. With regard to microbiological diagnostic, conventional culture of periprosthetic biopsies and sonication of explant material were performed. In addition, histology and non-specific inflammatory markers (CRP, leukocytes) were recorded. RESULTS: A total of 78 patients with PJI and 62 aseptic controls were included. From both microbiological methods (conventional culture / sonication), Staphyloccus (S.) epidermidis and S. aureus were detected most frequently. However, compared to the conventional microbiology, a higher sensitivity was calculated for sonication, albeit with a lower specificity in relation to a PJI. In two logistic regression models for the significance of all diagnostic parameters in PJI, the AUC was 0.92 and 0.96 with histology in particular making the decisive contribution in both models (p < 0. 001, both models). CONCLUSION: Since histology showed the highest accuracy in the current study, its importance in the PJI criteria should be reevaluated. Sonication shows a high sensitivity for germ detection with a lower specificity and should only be used in combination with the conventional culture for microbiolgical diagnostics.

PATHFINDER-CHD: prospective registry on adults with congenital heart disease, abnormal ventricular function, and/or heart failure as a foundation for establishing rehabilitative, prehabilitative, preventive, and health-promoting measures: rationale, aims, design and methods.

BACKGROUND: Adults with congenital heart defects (ACHD) globally constitute a notably medically underserved patient population. Despite therapeutic advancements, these individuals often confront substantial physical and psychosocial residua or sequelae, requiring specialized, integrative cardiological care throughout their lifespan. Heart failure (HF) is a critical challenge in this population, markedly impacting morbidity and mortality. AIMS: The primary aim of this study is to establish a comprehensive, prospective registry to enhance understanding and management of HF in ACHD. Named PATHFINDER-CHD, this registry aims to establish foundational data for treatment strategies as well as the development of rehabilitative, prehabilitative, preventive, and health-promoting interventions, ultimately aiming to mitigate the elevated morbidity and mortality rates associated with congenital heart defects (CHD). METHODS: This multicenter survey will be conducted across various German university facilities with expertise in ACHD. Data collection will encompass real-world treatment scenarios and clinical trajectories in ACHD with manifest HF or at risk for its development, including those undergoing medical or interventional cardiac therapies, cardiac surgery, inclusive of pacemaker or ICD implantation, resynchronization therapy, assist devices, and those on solid organ transplantation. DESIGN: The study adopts an observational, exploratory design, prospectively gathering data from participating centers, with a focus on patient management and outcomes. The study is non-confirmatory, aiming to accumulate a broad spectrum of data to inform future hypotheses and studies. PROCESSES: Regular follow-ups will be conducted, systematically collecting data during routine clinical visits or hospital admissions, encompassing alterations in therapy or CHD-related complications, with visit schedules tailored to individual clinical needs. ASSESSMENTS: Baseline assessments and regular follow-ups will entail comprehensive assessments of medical history, ongoing treatments, and outcomes, with a focus on HF symptoms, cardiac function, and overall health status. DISCUSSION OF THE DESIGN: The design of the PATHFINDER-CHD Registry is tailored to capture a wide range of data, prioritizing real-world HF management in ACHD. Its prospective nature facilitates longitudinal data acquisition, pivotal for comprehending for disease progression and treatment impacts. CONCLUSION: The PATHFINDER-CHD Registry is poised to offer valuable insights into HF management in ACHD, bridging current knowledge gaps, enhancing patient care, and shaping future research endeavors in this domain.

Bronchodilator Response in Post-COVID-19 Patients Undergoing Pulmonary Rehabilitation.

INTRODUCTION: SARS-CoV-2 infections can result in a broad spectrum of symptoms from mild to life-threatening. Long-term consequences on lung function are not well understood yet. METHODS: In our study, we have examined 134 post-COVID patients (aged 54.83 ± 14.4 years) with dyspnea on exertion as a leading symptom 6 weeks to 24 months after a SARS-CoV-2 infection for bronchodilator responsiveness during their stay in our pulmonary rehabilitation clinic. RESULTS: Prior to bronchial dilation, 6 out of 134 patients (4.47%) presented an FEV1/FVC ratio below lower limit of normal (Z-score = -1.645) indicative of an obstructive airway disease. Following inhalation of a ß2-adrenergic agonist we measured a mean FEV1 increase of 181.5 mL in our cohort, which was significantly elevated compared to a historical control group (ΔFEV1 = 118 mL). 28.7% of the patients showed an increase greater than 200 mL and 12% displayed a significant bronchodilation response (>200 mL ΔFEV1 and >12% FEV1 increase). Interestingly, no significant difference in bronchial dilation effect was observed when comparing patients hospitalized and those non-hospitalized during the course of their SARS-CoV-2 infection. CONCLUSION: Our data provide evidence for increased prevalence of obstructive ventilatory defects and increased bronchodilator responsiveness in patients with persisting symptoms after COVID-19. Depending on the extent of this complication, post-COVID patients may benefit from an adapted ß2-inhalation therapy including subsequent reevaluation.

Impact of virtual reality on peri-interventional pain, anxiety and distress in a pediatric oncology outpatient clinic: a randomized controlled trial.

PURPOSE: Pain and anxiety-inducing interventions have a major impact on pediatric patients. Pain reduction by virtual reality (VR) during port and vein punctures is well studied. This study investigates peri-interventional reduction of pain, anxiety and distress using VR compared to the standard of care (SOC) in a pediatric oncology outpatient clinic. METHODS: In a randomized, controlled cross-over design, patients aged 6-18 years experience potentially painful interventions accompanied by VR. Observational instruments include NRS, FPS-r, BAADS, mYPAS-SF, PedsQL and SSKJ3-8R. All patients undergo two observations: SOC (A) and VR (B) in a randomized order. In addition, parents and staff are interviewed. Specific conditions for VR in an outpatient clinic setting derived from interprofessional focus group discussion are being explored. RESULTS: Between July 2021 and December 2022 57 eligible patients were included and randomized to the orders A/B (n = 28) and B/A (n = 29). Thirty-eight patients completed both observations. Characteristics in both groups did not differ significantly. More than half of the patients had no previous experience with VR, 5% decided to discontinue VR prematurely. Peri-interventional pain, anxiety and distress were significantly reduced by VR compared with SOC. 71% of patients and 76% of parents perceived punctures with VR to be more relaxed than previous ones. 95% of patients perceived fun with VR goggles. Detailed questionnaires on individual stress and anxiety were returned from 26 of 38 patients. Focus group discussion with staff yielded evidence for successful implementation of VR in an outpatient clinic. CONCLUSIONS: The present study shows that VR can be used for peri-interventional reduction of pain, anxiety, and distress in the special environment of a pediatric outpatient clinic. Specific conditions must be met for successful implementation. Further studies are needed to identify particularly susceptible patients and to illuminate alternatives for distraction that are feasible to implement with limited resources. TRIAL REGISTRATION NUMBER: (ClinicalTrials.gov ID): NCT06235723; 01/02/2024; retrospectively registered. This study adheres to the standard checklist of CONSORT guidelines.

Optimal Selection of Sampling Points within Sewer Networks for Wastewater-Based Epidemiology Applications.

Wastewater-based epidemiology (WBE) has great potential to monitor community public health, especially during pandemics. However, it faces substantial hurdles in pathogen surveillance through WBE, encompassing data representativeness, spatiotemporal variability, population estimates, pathogen decay, and environmental factors. This paper aims to enhance the reliability of WBE data, especially for early outbreak detection and improved sampling strategies within sewer networks. The tool implemented in this paper combines a monitoring model and an optimization model to facilitate the optimal selection of sampling points within sewer networks. The monitoring model utilizes parameters such as feces density and average water consumption to define the detectability of the virus that needs to be monitored. This allows for standardization and simplicity in the process of moving from the analysis of wastewater samples to the identification of infection in the source area. The entropy-based model can select optimal sampling points in a sewer network to obtain the most specific information at a minimum cost. The practicality of our tool is validated using data from Hildesheim, Germany, employing SARS-CoV-2 as a pilot pathogen. It is important to note that the tool's versatility empowers its extension to monitor other pathogens in the future.

A Novel Tool for the Rapid and Transparent Verification of Reference Intervals in Clinical Laboratories.

Background/Objectives: We present a software package called reflimR (Version 1.0.6), which enables rapid and transparent verification of reference intervals from routine laboratory measurements. Our method makes it easy to compare the results with specified target values and facilitates the interpretation of deviations using traffic light colors. Methods: The algorithm includes three procedural steps: (a) definition of an appropriate distribution model, based on Bowley's quartile skewness, (b) iterative truncation, based on a modified boxplot method to obtain the central 95% of presumably inconspicuous results, and (c) extrapolation of reference limits from a truncated normal quantile-quantile plot. Results: All algorithms have been combined into one consolidated library, which can be called in the R environment with a single command reflim (x). Using an example dataset included in the package, we demonstrate that our method can be applied to mixed data containing a substantial proportion of pathological values. It leads to similar results as the direct guideline approach as well as the more sophisticated indirect refineR software package. As compared to the latter, reflimR works much faster and needs smaller datasets for robust estimates. For the interpretation of the results, we present an intuitive color scheme based on tolerance ranges (permissible uncertainty of laboratory results). We show that a relatively high number of published reference limits require careful reevaluation. Conclusions: The reflimR package closes the gap between direct guideline methods and the more sophisticated indirect refineR method. We recommend reflimR for the rapid routine verification of large amounts of reference limits and refineR for a careful analysis of unclear or doubtful results from this check.

Quantification of ventricular stress in univentricular hearts during early childhood using age-independent zlog-NT-proBNP.

BACKGROUND: Children with univentricular hearts (UVH) undergo up to three palliative surgical procedures to achieve complete circulatory separation (Fontan circulation). As a marker of cardiac wall stress, NT-proBNP is a promising tool to assess systemic ventricular load in these patients. However, different reference intervals (RI) apply to each stage, as NT-proBNP is highly age-dependent. METHODS: Children undergoing systemic-to-pulmonary (SP) shunt placement (stage 1), bidirectional cavopulmonary shunt (BCPS, stage 2) or total cavopulmonary connection (TCPC, stage 3) between 2011 and 2021 with NT-proBNP measurement within 7 days before surgery were included. Furthermore, outpatients after TCPC with NT-proBNP measurement were enrolled. Biomarker levels were evaluated using its age-adjusted z-score ("zlog-NT-proBNP"; age-independent RI, -1.96 to +1.96), allowing comparison between different stages and revealing changes in systemic ventricular load independent of the marked physiological decline in RI with age. RESULTS: Overall, 289 children (227 before, 62 after TCPC) met the eligibility criteria. Median time between blood sampling and surgery (SP shunt/BCPS/TCPC) was 2 [1-3] days and 3.2 [2.0-4.5] years after TCPC. Age-adjusted zlog-NT-proBNP levels were 3.47 [2.79-3.93] in children with native UVH (before SP shunt), 3.10 [1.89-3.58] at stage 1 (before BCPS), 1.08 [0.51-1.88] at stage 2 (before TCPC), and 1.09 [0.72-1.75] at stage 3 (after TCPC/Fontan completion). Consequently, BCPS revealed the strongest decrease (median - 2.02 logarithmized standard deviations, p < 0.001). CONCLUSIONS: In children with UVH undergoing staged Fontan palliation, zlog-NT-proBNP is a highly promising tool for course assessment of systemic ventricular load, independent of the age-related decline in physiological NT-proBNP concentration.

Longitudinal analysis of systemic ventricular function and atrioventricular valve function after the Norwood procedure.

OBJECTIVES: To evaluate longitudinal systemic ventricular function and atrioventricular valve regurgitation in patients after the neonatal Norwood procedure. METHODS: Serial postoperative echocardiographic images before Fontan completion were assessed in neonates who underwent the Norwood procedure between 2001 and 2020. Ventricular function and atrioventricular valve regurgitation were compared between patients with modified Blalock-Taussig shunt and right ventricle to pulmonary artery conduit. RESULTS: A total of 335 patients were identified including 273 hypoplastic left heart syndrome and 62 of its variants. Median age at Norwood was 8 (7-12) days. Modified Blalock-Taussig shunt was performed in 171 patients and the right ventricle to pulmonary artery conduit in 164 patients. Longitudinal ventricular function and atrioventricular valve regurgitation were evaluated using a total of 4352 echocardiograms. After the Norwood procedure, ventricular function was initially worse (1-30 days) but thereafter better (30 days to stage II) in the right ventricle to pulmonary artery conduit group (P < 0.001). After stage II, the ventricular function was inferior in the right ventricle to the pulmonary artery conduit group (P < 0.001). Atrioventricular valve regurgitation between the Norwood procedure and stage II was more frequent in the modified Blalock-Taussig shunt group (P < 0.001). After stage II, there was no significant difference in atrioventricular valve regurgitation between the groups (P = 0.171). CONCLUSIONS: The effect of shunt type on haemodynamics after the Norwood procedure seems to vary according to the stage of palliation. After the Norwood, the modified Blalock-Taussig shunt is associated with poorer ventricular function and worse atrioventricular valve regurgitation compared to right ventricle to pulmonary artery conduit. Whereas, after stage II, modified Blalock-Taussig shunt is associated with better ventricular function and comparable atrioventricular valve regurgitation, compared to the right ventricle to pulmonary artery conduit.

Parenting and Gender as Impact Factors for Social Participation, Quality of Life, and Mental Health in Long COVID.

OBJECTIVES: This study aims to investigate the impact of gender and parental tasks on social participation, health-related quality of life (hrQoL), and mental health in persons with long COVID. METHODS: A mixed-methods approach was followed including a cross-sectional web-based survey and semi-structured interviews. Multivariable linear regressions were used to quantify the effect of gender and parenting tasks on social participation, hrQoL, and mental health. Qualitative data from interviews with participants experiencing long COVID symptoms was analyzed using content analysis. RESULTS: Data from 920 participants in the quantitative study and 25 participants in the qualitative study was analyzed. Parenting tasks were associated with increased impairments in family and domestic responsibilities in persons with long COVID compared to lower impairments in persons without long COVID (P = .02). The qualitative data indicate that coping with long COVID and pursuing parenting tasks limit participants' ability to perform leisure activities and attend social gatherings. In long COVID, men had higher anxiety symptoms than women, and in those without long COVID, the opposite was observed (P < .001). In the qualitative study, participants expressed feelings of dejection and pessimism about their future private, occupational, and health situations. No differences between the genders could be observed. CONCLUSIONS: Long COVID is associated with impairments in family and domestic responsibilities in individuals who have parenting tasks. Among participants with long COVID, anxiety symptoms are higher in men than women.

Evaluating the Feasibility, Acceptance, and Beneficial Effects of Online Occupational Therapy for Post-COVID-19 Condition: Protocol for a Randomized Controlled Trial (ErgoLoCo Study).

BACKGROUND: Post-COVID-19 syndrome (PCS; also known as "long COVID") is a relatively novel disease comprising physical, psychological, and cognitive complaints persisting several weeks to months after acute infection with SARS-CoV-2. Approximately 10% of patients with COVID-19 are affected by long-term symptoms. However, effective treatment strategies are lacking. The ErgoLoCo (Occupational Therapy [Ergotherapie] for Long COVID) study was designed to develop and evaluate a novel occupational therapy (OT) concept of online delivery of therapy for long COVID. OBJECTIVE: The primary study objective is to assess the feasibility of the online OT intervention in PCS. Secondary aims include the evaluation of online OT concerning cognitive problems, occupational performance, and social participation. METHODS: This randomized controlled interventional pilot study involves parallel mixed methods process analyses and a realist evaluation approach. A total of 80 clients with PCS aged at least 16 years will be recruited into two interventional groups. The control cohort (watch and wait) comprises 80 clients with long COVID. Treatment is provided through teletherapy (n=40) or delivery of prerecorded videos (n=40) using the same standardized OT concept twice weekly over 12 weeks. Analyses of quantitative questionnaires and qualitative interviews based on the theoretical framework of acceptability will be performed to assess feasibility. Focus group meetings will be used to assess how acceptable and helpful the intervention was to the participating occupational therapists. Standardized tests will be used to assess the initial efficacy of the intervention on neurocognitive performance; limitations in mobility, self-care, and everyday activities; pain; disabilities; quality of life (QoL); social participation; and anxiety and depression in PCS, and the possible effects of online OT on these complaints. RESULTS: The German Ministry of Education and Research provided funding for this research in March 2022. Data collection took place from October 2022 to August 31, 2023. Data analysis will be completed by the end of April 2024. We anticipate publishing the results in the fall of 2024. CONCLUSIONS: Despite the enormous clinical need, effective and scalable treatment options for OT clients who have PCS remain scarce. The ErgoLoCo study will assess whether online-delivered OT is a feasible treatment approach in PCS. Furthermore, this study will assess the effect of the intervention on cognitive symptoms, QoL, and occupational performance and participation in everyday life. Particular emphasis will be placed on the experiences of clients and occupational therapists with digitally delivered OT. This study will pave the way for novel and effective treatment strategies in PCS. TRIAL REGISTRATION: German Clinical Trial Registry DRKS00029990; https://drks.de/search/de/trial/DRKS00029990. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50230.

Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS).

Post-acute COVID-19 vaccination syndrome (PACVS) is a chronic disease triggered by SARS-CoV-2 vaccination (estimated prevalence 0.02%). PACVS is discriminated from the normal post-vaccination state by altered receptor antibodies, most notably angiotensin II type 1 and alpha-2B adrenergic receptor antibodies. Here, we investigate the clinical phenotype using a study registry encompassing 191 PACVS-affected persons (159 females/32 males; median ages: 39/42 years). Unbiased clustering (modified Jaccard index) of reported symptoms revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (>80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, and vasomotor dysfunction; (ii) cardiovascular impairment; and (iii) cognitive impairment, headache, and visual and acoustic dysfunctions were also frequently represented. Notable abnormalities of standard serum markers encompassing increased interleukins 6 and 8 (>80%), low free tri-iodine thyroxine (>80%), IgG subclass imbalances (>50%), impaired iron storage (>50%), and increased soluble neurofilament light chains (>30%) were not associated with specific symptoms. Based on these data, 131/191 participants fit myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and simultaneously also several other established dysautonomia syndromes. Furthermore, 31/191 participants fit none of these syndromes. In conclusion, PACVS could either be an outlier of ME/CFS or a dysautonomia syndrome sui generis.

Association of long COVID with health-related Quality of Life and Social Participation in Germany: Finding from an online-based cross-sectional survey.

Purpose: This study aims to examine the health-related Quality of Life (hrQoL) and social participation in participants with Long COVID compared to participants without symptoms after COVID-19 and participants with no prior SARS-CoV-2 infection. Methods: A cross-sectional online survey was conducted in Germany. The non-random sample consists of participants 18 years or older. Participants were divided in three groups: Lg COVID with a prior SARS-CoV-2 infection and new or persistent symptoms 28 days after infection, ExCOVID with a prior SARS-CoV-2 infection and without new or persistent symptoms after 28 days, and NoCOVID when participants had no prior SARS-CoV-2 infection. EQ-5D-3L was used as hrQoL measure and the Index for the Assessment of Health Impairments (IMET) to reflect social participation. Descriptive and inferential statistics were performed. Results: A total of 3188 participants were included in the analysis (1421 Lg COVID, 260 ExCOVID, 1507 NoCOVID). Lg COVID was associated with the lowest EQ-5D-3L index values (p < 0.001), Visual Analogue Scale (VAS) scores (p < 0.001), and IMET (p < 0.001) scores followed by NoCOVID and ExCOVID. After adjusting for sociodemographic and medical conditions in a multivariable model Long COVID was still associated with lower hrQoL compared to NoCOVID (p < 0.001). About 10% of Lg COVID participants showed no health impairments in all EQ-5D dimensions while 51.1% of NoCOVID and 60% of ExCOVID participants showed no health impairments. Conclusion: This study highlights the impairments of persons with Long COVID on hrQoL and social participation compared to individuals without Long COVID in Germany. Trial registration: German Clinical Trial Registry, DRKS00026007.

Impact of pulsatile pulmonary blood flow on cardiopulmonary exercise performance after the Fontan procedure.

Objective: To evaluate the exercise capacity in patients following Fontan-Kreutzer, Fontan-Björk, and total cavopulmonary connection (TCPC). Methods: Patients who performed exercise capacity tests at least once after the Fontan procedure between 1979 and 2007 were included. Patients after Fontan-Björk procedure were divided into 2 groups according to the pulmonary blood flow (PBF) pattern: patients with pulsatile PBF and those without. Peak oxygen uptake (VO2) was measured and percent-predicted VO2 was calculated. Results: A total of 227 patients were nominated. The types of Fontan procedure included Fontan-Kreutzer in 48 (21.1%) patients, Fontan-Björk in 38 (16.7%); 11 (4.8%) with pulsatile PBF and 27 (11.9%) without pulsatile PBF; and TCPC in 141 (62.1%). Median age at the Fontan procedure was 4.5 years (interquartile range, 2.1-8.2 years). A total of 978 cardiopulmonary exercise tests were performed at median follow-up of 17.7 years (interquartile range, 11.3-23.4 years) postoperatively. Analysis using linear mixed-effects models demonstrated that percent-predicted VO2 was greater in patients with pulsatile PBF after Fontan-Björk compared with patients after other types of Fontan procedure (P < .001). The same results were obtained when the longitudinal percent predicted VO2 was performed using only patients with tricuspid atresia and double inlet left ventricle (P < .001). Conclusions: Among long-term survivors after various types of Fontan procedures, patients with pulsatile PBF after the Fontan-Björk procedure demonstrated better exercise performance compared to those after TCPC, those after the Fontan-Kreutzer procedure, and those after the Fontan-Björk procedure with non-pulsatile PBF. The results implicate the importance of pulsatile PBF to maintain the Fontan circulation.