BackgroundPrimary infection with the Epstein-Barr virus (EBV) in early childhood is often asymptomatic, whereas infection with EBV during adolescence or adulthood may lead to infectious mononucleosis (IM). Sometimes severe complications like hepatitis, spleen rupture, or myocarditis may appear during IM. Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of regulatory immune cells with immunosuppressive activities. However, not much is known about the role of MDSC in IM. We assessed a clinical translational prospective study to examine the role of MDSC during the early and late phases of IM in pediatric patients.MethodWe performed a longitudinal analysis of PMN-like, M-like, and e-like MDSC frequencies in 37 pediatric patients during the early (V1 < 28 days after symptom onset (Tonset), V2 four to six weeks after Tonset) and late phases (V3 = six to 12 months after Tonset) of IM using flow cytometry-based analyses. In addition, we determined the correlation of frequencies of MDSC-like subpopulations with the complexity and severity of laboratory, clinical, and virological IM features.ResultsWe detected comparable frequencies of total MDSC-like cells during the course of IM (V1 median: 22.87%, V2 median: 16.10%, and V3 median: 16.58% of CD33+ cells, respectively). However, we observed temporal dynamics of the MDSC-like subpopulations PMN-like, M-like, and e-like MDSC during the early and late phases of IM. The frequency of PMN-like MDSC decreased significantly from V1 to V2 (P < 0.001) and from V1 to V3 (P < 0.001). In contrast, the frequency of M-like MDSC decreased significantly from V1 to V2 (P = 0.015) and increased from V2 to V3 (P < 0.001). e-like MDSC frequencies increased significantly from V1 to V3 (P < 0.001). We observed an increase in the proportion of PMN-like MDSC with the IM-complexity and severity laboratory score and ferritin levels.ConclusionOur data highlights the rationale for in-depth analyses of MDSC subpopulations in further studies on IM and contributes to obtaining a more differentiated picture of the ongoing changes in MDSC-like cell distribution and the relationship between frequencies of MDSC-like cells and the complexity and severity of laboratory, clinical, and virological IM features.

Post-COVID condition (PCC) in children and young people (CYP, PCCcyp) remains a significant health burden. Early identification of patients at risk for severe disease, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is crucial for timely and adequate care. This monocentric, observational registry study, performed at a tertiary pediatric hospital in Germany, included CYP aged 7–25 years with PCCcyp at diagnosis. Standardized clinical assessment tools and patient-reported outcome measures were applied, including the novel Munich Long COVID Symptom Questionnaire (MLCSQ). Severe PCC was defined by chronic symptom clusters, Fatigue Severity Scale (FSS), Total Composite Autonomic Symptom Score-31 (COMPASS-31), SF-36 composite scores, Bell Score, and confirmed ME/CFS diagnosis. Among 120 participants, severe PCCcyp was associated with a higher number of acute symptoms (ORadj 1.22, P < 0.001), acute orthostatic intolerance (ORadj 9.87, P = 0.002), acute trouble concentrating (ORadj 11.8, P = 0.005), and female sex (OR 3.31, P = 0.031). Categorizing acute symptoms at a threshold of ≥ 12 yielded optimal model performance (AUC 0.857; sensitivity 65.6

OBJECTIVE:Measuring the utilisation of healthcare services in children and adolescents with symptoms suggesting post-COVID-19 condition (PCC) until their presentation at specialised outpatient clinics (SOC). METHODS:117 patients (aged 4-17 years) with symptoms suggesting PCC were recruited for study participation in SOCs of the comprehensive care network 'Post-COVID Kids Bavaria' for children and adolescents with PCC in Bavaria, Germany. Information on healthcare utilisation from their initial SARS-CoV-2 infection until presentation at an SOC was collected via telephone interviews with parents. RESULTS:Participants had a median of 6.5 physician contacts (Q1-Q3: 3.8-11.5), mainly in person (99.1%, n=116) and rarely used telemedicine (21.4%, n=25). Contacts were mainly with paediatricians (72.6%, n=85), followed by general practitioners (46.2%, n=50). Non-pharmacological measures were used by 56 participants (47.9 %), with therapies by Heilpraktiker and osteopaths being used most commonly (30.8%, n=36). 76 participants (65.0%) were prescribed medications, and 71 (60.7%) used non-prescribed medications or supplements. CONCLUSIONS:Children and adolescents with PCC symptoms frequently consult healthcare services, often self-initiated measures provided by Heilpraktiker and osteopaths, until their presentation at an SOC. This may be due to unclear care pathways. Paediatricians and general practitioners are key providers, making their expertise and strong connections with SOCs essential for early diagnosis and appropriate treatment.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystemic disorder mostly triggered by viral infections, with core symptoms including post-exertional malaise (PEM), fatigue, pain, and cognitive dysfunction. Its prevalence has increased significantly in the context of the coronavirus disease 2019 (COVID-19) pandemic. Despite its severity and impact on patients' quality of life, ME/CFS remains poorly understood. On May 12 and 13, 2025, the 3rd International Conference hosted by the Charité Fatigue Center brought together nearly 200 researchers from various disciplines on-site, and around 3,700 participants online to discuss recent advances in ME/CFS research, diagnostics, clinical care, and therapeutic trials. The program featured 33 lectures by international experts on key topics such as post-COVID syndrome (PCS), care structures, and pathophysiological mechanisms including cardiovascular dysregulation, immune dysregulation, autoimmune mechanisms, and metabolic dysfunction. In addition, results from clinical trials addressing disease mechanisms, including those specifically targeting autoantibodies, were presented. While public awareness and funding opportunities have increased in the wake of the pandemic and the emergence of PCS, ME/CFS remains severely underresearched. Sustained and adequately funded research efforts are urgently required to advance understanding, identify diagnostic markers, and develop targeted therapeutic interventions.

BackgroundThe Epstein-Barr virus (EBV) is an oncogenic herpesvirus that establishes lifelong infections in more than 90% of the human population. EBV infection is typically diagnosed using serological assays, which also distinguish between acute and persistent infection. However, current diagnostic approaches rely on a limited set of viral proteins and may therefore fail to detect disease-specific antibody signatures associated with EBV-related cancers or autoimmune diseases. Comprehensive profiling of humoral responses against the complete EBV proteome could improve the sensitivity and specificity of serological diagnostics.MethodsWe developed a serological multiplex assay covering all EBV proteins expressed in human cells, enabling measurement of virus-specific IgM, IgG, and IgA responses. The assay was evaluated using sera from healthy EBV carriers and EBV-negative controls. Near-infrared detection was employed to support quantitative analysis across a broad dynamic range. Performance was benchmarked against commercially available serological assays.ResultsThe multiplex assay demonstrated a broad dynamic range with linear quantification across several orders of magnitude. Comparative evaluation showed that the assay achieved sensitivity and specificity comparable to established commercial tests while enabling comprehensive antibody profiling against the full EBV proteome.ConclusionThis multiplex serological platform provides a robust approach for comprehensive characterization of EBV-specific humoral immune responses. By extending antibody profiling beyond the limited antigen panels used in routine diagnostics, the assay may facilitate the identification of novel biomarkers for EBV-associated cancers and autoimmune diseases. Future applications could contribute to improved diagnostic accuracy and support the development of targeted therapeutic strategies.

The epidemiology of suspected pediatric meningoencephalitis has shifted in the era of conjugate vaccines and multiplex PCR diagnostics, with viral pathogens now predominating over bacterial causes. Updated epidemiologic data are essential to adapt diagnostic and therapeutic algorithms to current clinical practice. This retrospective single-center study included children and adolescents <18 years who underwent lumbar puncture with cerebrospinal fluid multiplex PCR for suspected central nervous system infection at a tertiary-care pediatric hospital in Germany between 2016 and 2024. Clinical, laboratory, and outcome data were extracted from electronic medical records. Cerebrospinal fluid was analyzed using the BioFire® FilmArray® Meningitis/Encephalitis Panel. Statistical analyses included descriptive statistics, nonparametric group comparisons, receiver operating characteristic analyses. Among 1,198 included children, definite bacterial meningitis was diagnosed in 13 (1.1%), definite viral meningitis in 80 (6.7%), aseptic meningitis of unknown etiology in 131 (11.0%), confirmed/probable encephalitis in 53 (4.4%), and possible encephalitis in 34 (2.8%). Bacterial meningitis accounted for 5.8% of all meningitis cases. A causative pathogen was identified in all bacterial meningitis cases, most commonly Streptococcus pneumoniae (n = 7). Enterovirus (n = 52) and parechovirus (n = 9) predominated in viral meningitis, whereas an infectious etiology was identified in only 13 of 53 confirmed/probable encephalitis cases. The Bacterial Meningitis Score showed a sensitivity of 80.0% and a specificity of 57.6%. The recently published UK-ChiMES-pre- and post-lumbar puncture scores demonstrated sensitivities of 84.6% and 76.9% and specificities of 86.3% and 92.7%, respectively. Bacterial meningitis was rare in this contemporary cohort, while viral and etiologically unresolved infections predominated despite routine multiplex PCR diagnostics. Clinical prediction scores supported risk stratification, with the UK-ChiMES-pre–lumbar puncture score showing the most favorable balance between sensitivity and specificity and potential to guide diagnostic decisions and antiinfective therapy.

The epidemiology of suspected pediatric meningoencephalitis has changed in the era of conjugate vaccines and multiplex PCR. Updated epidemiologic data are needed to adapt diagnostic and therapeutic algorithms to current practice. This retrospective single-center study included children < 18 years who underwent lumbar puncture with cerebrospinal fluid multiplex PCR for suspected central nervous system infection at a tertiary pediatric hospital in Germany between 2016 and 2024. Clinical, laboratory, and outcome data were extracted from electronic medical records. Cerebrospinal fluid was analyzed using the BioFire® FilmArray® Meningitis/Encephalitis Panel. Statistical analyses included descriptive statistics, nonparametric comparisons, and receiver operating characteristic analyses. Among 1,198 children, definite bacterial meningitis was diagnosed in 13 (1.1

Existing healthcare infrastructure struggles to meet the complex care required for pediatric Post-COVID Syndrome (pPCS). Telemonitoring offers potential to enhance care access, reduce patient burden, and ensure continuity. This study introduces and evaluates a novel, multimodal telemonitoring concept for pPCS with high translational potential for broader pediatric chronic and post-infectious conditions. Telemonitoring included a patient app, digital sensors (spirometer, smartwatch), Patient Reported Outcome Measures, chat/video consultations (VC), and a medical telemonitoring platform. Patients aged 12–17 years with diagnosed PCS were recruited from two pPCS outpatient university clinics in Bielefeld and Munich, Germany. Monitoring lasted three months. Evaluation focused on feasibility, adherence, acceptance, and usability, using monitoring data, the System Usability Scale (SUS), Technology Usage Inventory (TUI), and a custom survey completed by patients and parents. 30 patients (mean age: 15y ± 1.9; 57

Children, adolescents, and young adults (CYP) with postacute infection and vaccination syndromes (PAIVS), and/or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), experience profound loss in activity and participation. We introduce and psychometrically validate two new brief, age-adapted, and domain-specific questionnaires for clinical use assessing activity and participation in this vulnerable patient group. For this, 91 patients (aged 10–25 years) were assessed at the Munich Chronic Fatigue Center (MCFC) from 12/2022 to 11/2024. We designed the MCFC Activity Scale and MCFC Participation Scale and assessed construct validity using confirmatory factor analysis for both questionnaires. Reliability was evaluated via Cronbach’s α. Factor-based MCFC Activity and Participation Scores (0–100) were derived and correlated with Bell Score, FSS, DSQ-PEM, and SF-12 Component Summary Scales (PCS and MCS). Discrimination for ME/CFS was evaluated using ROC analyses. Participants (mean age 15.6 ± 2.4 years) were predominantly female (64

To identify ICD-10-GM codes recorded in the year preceding a Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) diagnosis, we conducted a 1:5 matched case–control study using statutory health insurance data of 6–27-year-olds with ME/CFS (ICD-10-GM: G93.3, 2020–2022). Cases (n = 6,077) were matched 1:5 to controls by birth year, sex, and postal code. ICD-10-GM codes from the preceding year were analyzed using multivariable conditional logistic regression, reporting odds ratios (OR) and 95% confidence intervals. Most cases were female and aged 18–27 years. Forty-four ICD-10-GM code classes were associated with increased and four with decreased odds, spanning 13 diagnostic chapters. Most associations were in chapters F (mental/behavioral disorders), R (respiratory diseases), and M (musculoskeletal disorders). Frequent conditions included fatigue, depression, pain disorders, and somatoform disorders (≥ 10% in cases; ORs 1.11–2.19. Rare diagnoses (≤ 1% prevalence), such as fibromyalgia (OR 2.08, 95% CI: 1.20–3.59) and mild cognitive impairment (2.93, 1.21–7.10), were strongly associated. Four COVID-19 or vaccination-related code classes were identified, with post-COVID-19 condition showing the highest OR (3.84, 2.97–4.98). Several ICD-10-GM codes, including COVID-19 related codes, were associated with later ME/CFS diagnoses. Prospective studies should clarify timing relative to ME/CFS onset, and distinguish between pre-existing conditions, comorbidities, early manifestations, or misdiagnoses.

Objectives:Central nervous system (CNS) infections in children require rapid diagnostic evaluation and prompt empiric antimicrobial therapy. However, clinical presentation is often non-specific, leading to frequent use of broad-spectrum antibiotics while awaiting cerebrospinal fluid (CSF) results. We evaluated antibiotic treatment modifications during the diagnostic work-up and quantified changes in antibiotic spectrum coverage (ASC) before and after lumbar puncture (LP). Patients and methods:We conducted a retrospective single-centre study including children <18 years who underwent LP for suspected CNS infection between January 2016 and December 2024. CSF was analysed using the BioFire® FilmArray® Meningitis/Encephalitis (ME) Panel. Antibiotic treatment modifications after LP-related diagnostic information became available were assessed descriptively. Paired ASC scores before and after LP were compared using the Wilcoxon signed-rank test among treated children. Results:Among 1198 children undergoing LP, 730 (60.9%) received antibiotic therapy. Antibiotic use was highest in neonates (227/246; 92.3%) and infants aged 29 days to <6 months (118/140; 84.3%) and lowest in adolescents (106/329; 32.2%). Treatment was modified after LP-related diagnostic information became available in 412/1198 children (34.4%). Among treated children, 313 (42.9%) underwent de-escalation, 99 (13.6%) escalation and 318 (43.6%) had no change. Overall, mean ASC decreased from 8.5 before LP to 6.6 afterwards (ΔASC -1.9; P < 0.001). Conclusions:LP-related diagnostic information was associated with frequent antibiotic treatment modification and reduced antibiotic spectrum coverage. These findings support integrated CSF diagnostics, including multiplex polymerase chain reaction, as a component of antimicrobial stewardship in children with suspected CNS infection.

Abstract Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children and young people (CYP) lacks validated diagnostic biomarkers. Post-exertional malaise (PEM) is central to case definitions and is usually assessed by patient report. We evaluated the feasibility and clinical value of handgrip strength (HGS) testing in PEM-reporting CYP referred for suspected ME/CFS. Methods In this prospective observational study at the Munich Chronic Fatigue Center for Young People (November 2022–November 2024), 147 patients (10–25 years) referred for the assessment of ME/CFS with positive DSQ-PEM screening and 83 healthy controls (HC) completed two HGS sessions (10 maximal grips/session; 3-s contraction/5-s rest; 60-minute inter-session break) using a digital dynamometer. We derived maximal force (Fmax), mean force (Fmean), fatigue ratio (FR = Fmax/Fmean), and recovery ratio (RR = Fmean session 2 / session 1). Analyses used repeated-measures ANCOVA, linear regression, partial Spearman correlations (adjusted for sex, age, and BMI), and proportional odds models for group membership (HC, noME/CFS, ME/CFS), reporting accuracy, and the C-statistic. Sensitivity analyses compared noME/CFS with confirmed CCC-ME/CFS. Results After clinical work-up, 84/147 (57%) patients were classified as ME/CFS (confirmed or probable) and 63/147 (43%) as noME/CFS. HGS test completion rate was high (session 1: 146/147, 99.3%; session 2: 142/147, 96.6%). Compared with HC, patients had substantially lower HGS (mean difference −9.93 kg, 95% CI: −12.00 to −7.85), and HGS indices correlated modestly with physical functioning (SF-12 PCS), but not with PEM duration. Both noME/CFS and ME/CFS groups differed from HC in absolute strength indices (Fmean, Fmax) and FR. RR differed between ME/CFS and HC, whereas no HGS index significantly separated noME/CFS from ME/CFS. In proportional odds models, each HGS index improved fit (all p < 0.001), but discrimination across HC, noME/CFS, and ME/CFS patients was moderate (accuracy 49.2–57.3% vs no-information rate 36.5%, with best performance for Fmean in session 2). In the CCC-restricted sensitivity analysis, discrimination between confirmed CCC-ME/CFS and noME/CFS was moderate (accuracy 62.8–70.7%; C-statistic 0.63–0.73), with best performance for absolute strength indices and RR. Conclusions Standardized two-session repeated HGS testing is feasible in CYP with chronic fatigue and self-reported PEM and provides an objective marker of functional impairment that aligns with physical health status but not with PEM duration. However, HGS alone shows limited ability to discriminate ME/CFS from other fatiguing noME/CFS conditions. HGS may be useful for quantitative phenotyping, patient stratification, and longitudinal outcome assessment rather than as a standalone diagnostic biomarker. Trial registration Not applicable.

IntroductionPostural orthostatic tachycardia syndrome (PoTS) can be associated with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Pediatric PoTS requires a “sustained” rise in orthostatic heart rate ≥40 bpm above supine heart rate (relative limit), often >120 bpm (absolute limit). However, the diagnostic criteria for PoTS in adolescents remain underexplored, particularly regarding the definition of “sustained” tachycardia, which poses challenges in clinical and research settings. This study examined orthostatic intolerance criteria, including PoTS, in adolescents with ME/CFS and healthy controls.MethodsMedical history of orthostatic intolerance was assessed by a semi-structured interview with 18 ME/CFS patients and 18 matched healthy controls (14–17 years). A passive 10-min standing test with minute-by-minute heart rate and blood pressure registration was performed. PoTS was diagnosed by a clinical expert based on current consensus criteria. Data were analyzed using Fisher's exact test and receiver operating characteristic analysis.ResultsAlthough history of orthostatic intolerance was positive in 15/18 ME/CFS [83%, 0.95 CI (61; 94)] and 3/18 healthy controls [17%, 0.95 CI (5.9; 39)], PoTS was diagnosed in only 7/18 ME/CFS [39%, 0.95 CI (20; 61)] vs. no healthy controls [0%, 0.95 CI (0; 18)]. Subgroups were identified, e.g., positive history of orthostatic intolerance yet physiological passive 10-min standing test, or negative history of orthostatic intolerance yet tachycardia in passive 10-minute standing test. PoTS diagnosis by the clinical expert matched best with the passive 10-min standing test alone when at least 60% of upright heart rate values were above one or both limits. The absolute limit was superior to the relative limit in distinguishing adolescents with and without PoTS.DiscussionPoTS was observed only in ME/CFS. In adolescents with ME/CFS, positive history of orthostatic intolerance, along with at least 60% of heart rate values above published upright-position limits, may allow non-experts to make a valid diagnosis, facilitating clinical care and future studies. Further research will show if these results can be generalized.

Postakute Infektions- und Vakzinierungssyndrome (PAIVS), einschließlich der myalgischen Enzephalomyelitis/des chronischen Fatigue-Syndroms (ME/CFS), betreffen auch Kinder und Jugendliche. Aufgrund heterogener Symptomatik, fehlender Biomarker und Kausaltherapien ist die Versorgung herausfordernd. Der Beitrag fasst den aktuellen Wissensstand zu PAIVS bei Kindern und Jugendlichen zusammen und liefert praktische Empfehlungen zum klinischen Management. Die Bündelung der Erkenntnisse erfolgte auf Basis internationaler Evidenz und klinischer Erfahrung der Autor*innen. Sie sind Initiator*innen bzw. Partner*innen des neuen, interdisziplinären und multiprofessionellen Projekts Pädiatrisches Netzwerk für die Versorgung und Erforschung von postakuten Folgen von COVID-19, ähnlichen postakuten Infektions- und Impfsyndromen sowie ME/CFS bei Kindern und Jugendlichen (PEDNET-LC), das bundesweit pädiatrische Versorgungs- und Forschungsstrukturen zu PAIVS auf- und ausbaut. Die PAIVS erfordern eine interdisziplinäre (differenzial-)diagnostische Abklärung. Insbesondere Screenings auf postexertionelle Malaise (PEM) als Kernsymptom von ME/CFS und auf orthostatische Intoleranz sind notwendig. Bei Vorliegen von PEM ist die Vermeidung einer Symptomverschlechterung durch Anpassung der Alltagsaktivitäten (Pacing) essenziell. In der Versorgung haben neben symptomatischen Therapien sozialmedizinische Maßnahmen zur Stärkung von Alltags- und Bildungsteilhabe einen hohen Stellenwert. Kinder und Jugendliche mit PAIVS benötigen eine individuell zugeschnittene, interdisziplinäre, multiprofessionelle und longitudinale Versorgung. Voraussetzungen sind gute intersektorale Zusammenarbeit sowie umfassende Aufklärung und Fortbildung zum Krankheitsbild. Das PEDNET-LC bietet die Chance, pädiatrische PAIVS-Versorgungs- und Forschungsstrukturen zu harmonisieren und weiterzuentwickeln.

A subset of patients with post-COVID-19 condition (PCC) fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To establish the diagnosis of ME/CFS for clinical and research purposes, comprehensive scores have to be evaluated. We developed the Munich Berlin Symptom Questionnaires (MBSQs) and supplementary scoring sheets (SSSs) to allow for a rapid evaluation of common ME/CFS case definitions. The MBSQs were applied to young patients with chronic fatigue and post-exertional malaise (PEM) who presented to the MRI Chronic Fatigue Center for Young People (MCFC). Trials were retrospectively registered (NCT05778006, NCT05638724). Using the MBSQs and SSSs, we report on ten patients aged 11 to 25 years diagnosed with ME/CFS after asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19. Results from their MBSQs and from well-established patient-reported outcome measures indicated severe impairments of daily activities and health-related quality of life. Conclusions: ME/CFS can follow SARS-CoV-2 infection in patients younger than 18 years, rendering structured diagnostic approaches most relevant for pediatric PCC clinics. The MBSQs and SSSs represent novel diagnostic tools that can facilitate the diagnosis of ME/CFS in children, adolescents, and adults with PCC and other post-infection or post-vaccination syndromes.