Persistent symptoms following SARS-CoV-2 infection, known as post-COVID syndrome (PCS), severely affect patients’ quality of life. Despite its prevalence, the underlying mechanisms and reliable biomarkers remain elusive. We investigated the antibody response and epitope recognition patterns in PCS to uncover potential biomarkers and pathophysiological links to immune dysregulation. Humoral immune responses were analyzed in PCS patients (n = 64) and convalescent controls (n = 64), matched for sex, age, and time since acute infection, further corroborated in three independent PCS validation cohorts (n = 420). PCS was associated with significantly elevated levels of neutralizing IgG, IgA and IgM antibodies targeting the SARS-CoV-2 receptor-binding domain and spike subdomains, but not against nucleocapsid or seasonal coronaviruses. Next, we identified three discriminatory PCS-specific spike epitopes, primarily located in the membrane-proximal region, as demonstrated by customized peptide microarray, ELISA and luminex methods. Binary logistic regression analysis revealed 82.8% specificity and 60.0% sensitivity for PCS diagnosis in seropositive patients. PCS-specific antibody levels correlated directly (D-Dimers) or inversely (6 min-walk distance, diffusion capacity) with clinical markers. These findings highlight enhanced spike-specific humoral responses in PCS and propose novel epitope-based biomarkers for PCS diagnosis and mechanistic insights. This project was supported by the German Ministry of Education and Research (BMBF; grant no. 01EP2105A). Viral Immunology (VIR)

ZusammenfassungRestriktive Lungenerkrankungen umfassen eine große Gruppe von unterschiedlichen Erkrankungen des Thoraxskeletts, der Pleura und des Lungenparenchyms, die durch eine Minderung des messbaren Lungenvolumens gekennzeichnet sind. In der Regel ist das Leitsymptom bei allen Erkrankungen eine mehr oder weniger schwere Belastungsatemnot und eine zunehmende Hypoxie. Im Schlaf finden sich bei allen Erkrankungen nächtliche Hypoxien, die zu einem fragmentierten, nicht erholsamen Schlaf führen. Die Gabe von Sauerstoff ist dann indiziert, wenn keine alveoläre Hypoventilation mit Hyperkapnie daraus folgt. Insbesondere Patienten mit thorakalrestriktiven Erkrankungen entwickeln eine chronische Hypoventilation, deren Therapie die nächtliche nichtinvasive Beatmung darstellt. Dagegen haben Patienten mit interstitiellen Lungenerkrankungen nur in Einzelfällen einen Nutzen von einer Heimbeatmung.

Abstract Background Emergence of periodic leg movements (PLM) on adaptive servo‐ventilation (ASV) is well known in patients with chronic heart failure and reduced ejection fraction (HFrEF), but its clinical significance remains unclear. We investigated the effect of ASV on the emergence of PLM with arousal (PLMA) in HFrEF patients with obstructive or central sleep apnea (OSA or CSA) and determined whether emergent PLMA modifies the effect of ASV on fatigue and sleepiness. Methods Sixty stable HFrEF patients (ASV n = 29, control n = 31) with moderate to severe OSA or CSA were included. Polysomnography (PSG) was obtained at baseline and after 12 weeks. Results In HFrEF patients with OSA and CSA, ASV significantly increased PLMA‐Index compared to control. ASV was associated with a significant reduction in Epworth sleepiness scale (ESS) and fatigue severity scale (FSS) in patients without emergent PLMA (52%) compared to those with emergent PLMA (48%; delta ESS: −3 (−3; 0) vs. 2 (−2; 4) p = 0.027; delta FSS: −1.3 (−2.1; 0.1) vs. −0.3 (−1.1; 1.7) p = 0.031) and compared to controls (0 (−1; 1) p = 0.039); (0.1 (−0.9; 0.4) p = 0.034). Conclusion ASV treatment increases PLMA in some HFrEF patients with OSA or CSA. On ASV treatment, patients reported only improved sleepiness and fatigue if no PLMA emerged.

Following SARS-CoV-2 infection, some individuals develop Long-COVID-syndrome lasting for more than 3 months. We analyzed blood samples from patients with Long-COVID, controls without persistent symptoms following SARS-CoV-2-infection and non-infected donors without a history of infection. Long-COVID patients showed clear signs of T cell hyper-activation predominantly in the CD8+ T cell subset with a 4-fold higher expression of CD25 and 2-fold more effector-memory T cells. Following polyclonal T cell stimulation, we found a 2-fold stronger upregulation of CD25 and a 7-fold higher release of IL-3 in Long-COVID. Intracellular staining revealed 5-fold more IL-3-expressing CD8+ T cells in Long-COVID, while GM-CSF, IFN-γ and IL-2 were much less upregulated. These changes correlated with the severity of Long-COVID and persisted for up to 18 months after infection. Our data reveal a pronounced and long-lasting CD8+ T cell hyper-activation and hyper-reactivity in Long-COVID and speak for a trial of T cell-immunosuppression in patients with Long-COVID.

Background Interstitial lung diseases (ILDs) comprise a group of more than 200 different subtypes. They vary widely in terms of incidence, prognosis and treatment, yet real-life data from Germany are sparse.Methods The prospective Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases (EXCITING)-ILD registry included patients with all different ILD subtypes from different healthcare settings. Follow-up ranged from 36 months to 5 years. Data were analysed descriptively. Baseline characteristics, diagnostic and treatment information are presented as absolute numbers and percentages. The Wilcoxon signed-rank sum test was used to quantify differences between groups. Line plots and bar plots were used for graphical presentation.Results A total of 601 patients (60.7% men, mean age 64.3 years) from 32 centres were included in the EXCITING-ILD registry. The most common subtypes were sarcoidosis with 26.6% (n=160) and idiopathic pulmonary fibrosis (IPF) with 25.3% (n=152). Pulmonary hypertension was present in 8.7% of patients (n=52), with high incidences in connective tissue disease-associated ILD (16.3%) and pneumoconiosis (27.3%). The mean forced vital capacity was 76.4% predicted, and the mean DLCO-SB (diffusing capacity for carbon monoxide) was 54.1% predicted. The mean time to diagnosis was 38.8 months (SD 64.4) and was significantly shorter when the diagnosis was made after multidisciplinary discussion (31.6 vs 49.2 months, p<0.001). The frequency of surgical lung biopsies decreased over time in the registry, whereas the proportion of cryobiopsies showed a notable increase. In IPF, the number of patients treated with antifibrotics increased from 35.2% before 2015 to 48.4% in 2019.Conclusion The EXCITING-ILD registry describes the frequency of ILD subtypes, ILD-related impairments, selected comorbidities and diagnostic and treatment patterns in a representative German population.

ZusammenfassungDas vorliegende Positionspapier (AWMF) zur Therapie der Sarkoidose der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP) wurde 2023 als deutschsprachige Ergänzung und Aktualisierung der internationalen Leitlinien der European Respiratory Society (ERS) aus dem Jahre 2021 verfasst. Sie enthält 5 im Konsensusverfahren abgestimmte Empfehlungen in Form von PICO-Fragen (Patients, Intervention, Comparison, Outcomes), die im Hintergrundtext der 4 Kapitel erläutert werden: Diagnosesicherung und Monitoring der Erkrankung unter Therapie, allgemeine Therapieempfehlungen, Therapie der Hautsarkoidose, Therapie der kardialen Sarkoidose.

Introduction: Invasive pneumococcal disease is a major cause of morbidity and mortality in infectious diseases. Selective reporting of antibiotic susceptibility test results might lead to a tailored antibiotic therapy and could therefore be an important antibiotic stewardship program intervention. The aim of this study was to analyse whether a switch to selective reporting of antibiotic test results leads to a more focused antibiotic therapy in patients with a bloodstream infection with Streptococcus pneumoniae. Methods: This study was performed as a retrospective cohort study at the University Hospital Regensburg, Germany. All blood cultures positive for Streptococcus pneumoniae between 2006 and 2021 were analysed. In 2014, a switch to selective reporting of antibiotic susceptibility test results omitting sensitivity results for agents not recommended was introduced. Results: Twenty-four hours after final antibiotic susceptibility test results were available, 20.9% before (BI) versus 15.4% after implementation (AI) of selective reporting of antibiotic test results received a narrow-spectrum penicillin, while only 2.3% BI versus 5.8% AI received a narrow-spectrum penicillin from the beginning. Conclusion: Selective reporting of antibiotic susceptibility test results without further antimicrobial stewardship interventions did not lead to a higher use of a narrow-spectrum penicillin in this study.

Introduction Face masks increase airway resistance, data on the actual extent of this effect are scarce. The aim of this study was to assess the effect of different mask types on clinical parameters during moderate exercise in healthy non-smokers, active smokers and patients with interstitial lung disease (ILD) without the need of oxygen therapy. Methods In a prospective observational pilot study participants performed a six-minute walk test without mask, with a surgical mask, a well-fitted FFP2 mask and with a valved FFP3 mask. Respiratory rate, blood pressure, heart rate, blood gas analysis parameters, dyspnoea and six-minute walk distance were measured. Data were analysed in an ANOVA model. Results 21 healthy participants, 17 active smokers without known pulmonary disease and 15 patients with interstitial lung disease were included. Participants with ILD had a significant lower walking distance, a higher respiratory rate and a lower pO2 when using FFP2 masks, but not with valved FFP3 masks or surgical masks compared to not wearing a mask. Conclusion For patients with ILD without the need of oxygen therapy wearing an FFP2 mask had a negative impact on pO2, respiratory rate and walking distance in the six-minute walk test. This effect was not seen with valved FFP3 masks or surgical masks.

Abstract Background Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with different disease trajectories. Progression (PF-ILD) occurs in up to 50% of patients and is associated with increased mortality. Methods The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for disease trajectories in different ILD. The course of disease was classified as significant (absolute forced vital capacity FVC decline > 10%) or moderate progression (FVC decline 5–10%), stable disease (FVC decline or increase < 5%) or improvement (FVC increase ≥ 5%) during time in registry. A second definition for PF-ILD included absolute decline in FVC % predicted ≥ 10% within 24 months or ≥ 1 respiratory-related hospitalisation. Risk factors for progression were determined by Cox proportional-hazard models and by logistic regression with forward selection. Kaplan-Meier curves were utilised to estimate survival time and time to progression. Results Within the EXCITING-ILD registry 28.5% of the patients died (n = 171), mainly due to ILD (n = 71, 41.5%). Median survival time from date of diagnosis on was 15.5 years (range 0.1 to 34.4 years). From 601 included patients, progression was detected in 50.6% of the patients (n = 304) with shortest median time to progression in idiopathic NSIP (iNSIP; median 14.6 months) and idiopathic pulmonary fibrosis (IPF; median 18.9 months). Reasons for the determination as PF-ILD were mainly deterioration in lung function (PFT; 57.8%) and respiratory hospitalisations (40.6%). In multivariate analyses reduced baseline FVC together with age were significant predictors for progression (OR = 1.00, p < 0.001). Higher GAP indices were a significant risk factor for a shorter survival time (GAP stage III vs. I HR = 9.06, p < 0.001). A significant shorter survival time was found in IPF compared to sarcoidosis (HR = 0.04, p < 0.001), CTD-ILD (HR = 0.33, p < 0.001), and HP (HR = 0.30, p < 0.001). Patients with at least one reported ILD exacerbation as a reason for hospitalisation had a median survival time of 7.3 years (range 0.1 to 34.4 years) compared to 19.6 years (range 0.3 to 19.6 years) in patients without exacerbations (HR = 0.39, p < 0.001). Conclusion Disease progression is common in all ILD and associated with increased mortality. Most important risk factors for progression are impaired baseline forced vital capacity and higher age, as well as acute exacerbations and respiratory hospitalisations for mortality. Early detection of progression remains challenging, further clinical criteria in addition to PFT might be helpful.

The present recommendations on the therapy of sarcoidosis of the German Respiratory Society (DGP) was written in 2023 as a German-language supplement and update of the international guidelines of the European Respiratory Society (ERS) from 2021. It contains 5 PICO questions (Patients, Intervention, Comparison, Outcomes) agreed in the consensus process, which are explained in the background text of the four articles: Confirmation of diagnosis and monitoring of the disease under therapy, general therapy recommendations, therapy of cutaneous sarcoidosis, therapy of cardiac sarcoidosis.