Purpose: Some patients experience long-term sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, despite a present post-COVID condition, defined as “any symptom lasting longer than 12 weeks,” only a subset of patients search for medical help and therapy. Method: We invited all adults with a positive real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 between March 2020 and September 2021 (n = 4091) in the city of Jena to answer a standardized questionnaire including demographic information, the course of the acute infection and current health status. K-means-clustering of quality of life (QoL) was used to explore post-COVID subgroups. Results: A total of 909 participants at a median interval of 367 (IQR 291/403) days after acute infection were included in the analysis. Of those, 643 (70.7%) complained of having experienced persistent symptoms at the time of the survey. Cluster analysis based on QoL revealed two subgroups of people with persistent post-COVID symptoms. Whereas 189/643 participants (29.4%) showed markedly diminished QoL, normal QoL was detected in 454/643 individuals (70.6%). Conclusion: Despite persistent symptoms being reported by nearly three quarters of participants, only one-third of these described a significant reduction in QoL (cluster 1), whereas the other two-thirds reported a near-normal QoL (cluster 2), thus indicating a differentiation between “post-COVID disease” and “post-COVID condition”. The prevalence of clinically relevant post-COVID disease was at least 20.7%. Health policies should focus on this subset.

A relevant proportion of patients suffer from long-lasting impairments following an acute SARS-CoV-2 infection. The proposed post-COVID syndrome (PCS) score may improve comparison in the course and classification of affected patients. A prospective cohort of 952 patients presenting to the post-COVID outpatient clinic at Jena University Hospital, Germany, was enrolled. Patients received a structured examination. PCS score was calculated per visit. A total of 378 (39.7%) and 129 (13.6%) patients of the entire population visited the outpatient clinic two or three times, respectively (female: 66.4%; age: 49.5 (SD = 13) years). The initial presentation took place, on average, 290 (SD = 138) days after acute infection. The most frequently reported symptoms were fatigue (80.4%) and neurological impairments (76.1%). The mean PCS scores of patients with three visits were 24.6 points (SD = 10.9), 23.0 points (SD = 10.9) and 23.5 points (SD = 11.5) (p = 0.407), indicating moderate PCS. Female sex (p < 0.001), preexisting coagulation disorder (p = 0.021) and coronary artery disease (p = 0.032) were associated with higher PCS scores. PCS is associated with a multitude of long-lasting problems. The PCS score has proven its capability to objectify and quantify PCS symptoms in an outpatient setting. The influence of therapeutic measures on various PCS aspects should be the subject of further analyses.

Background: In acute pancreatitis (AP), microcirculatory dysfunction and leukocyte activation contribute to organ damage, inflammation, and mortality. Given the role of macrophage activation, monocyte recruitment, and microthrombus formation in the early pathogenesis of AP, we examined the macrophage activation marker soluble mannose receptor (sCD206) and the endothelial function marker von Willebrand factor (vWF) in patients admitted for AP. Methods: In an exploratory analysis, serum sCD206 and plasma vWF were prospectively analyzed on day 1 and day 3 in 81 patients with AP admitted to the hospital. In addition, blood samples from 59 patients with early AP admitted to the intensive care unit and symptom onset < 24 h were retrospectively analyzed. Patients were dichotomized as per study protocol into two groups: (i) “non-severe edematous AP” including patients with mild AP without organ failure and patients with transient organ failure that resolves within 48 h and (ii) “severe/necrotizing AP” including patients with severe AP and persistent organ failure > 48 h and/or patients with local complications. Results: In the prospective cohort, 17% developed severe/necrotizing pancreatitis compared with 56% in the ICU cohort. Serum concentrations of sCD206 on admission were higher in patients with severe/necrotizing AP than in patients with non-severe edematous AP (prospective: 1.57 vs. 0.66 mg/l, P = 0.005; ICU: 1.76 vs. 1.25 mg/l, P = 0.006), whereas other inflammatory markers (leukocytes, C-reactive protein, procalcitonin) and disease severity (SOFA, SAPS II, APACHE II) did not show significant differences. Patients with severe/necrotizing AP had a greater increase in sCD206 than patients with non-severe edematous AP at day 3 in the prospective cohort. In contrast to routine coagulation parameters, vWF antigen levels were elevated on admission (prospective cohort: 375 vs. 257%, P = 0.02; ICU cohort: 240 vs. 184%, P = 0.03). When used as continuous variables, sCD206 and VWF antigen remained predictors of severe/necrotizing AP after adjustment for etiology and age in both cohorts. Conclusions: sCD206 identifies patients at risk of severe AP at earlier timepoints than routine markers of inflammation and coagulation. Prospective studies are needed to investigate whether incorporating early or repeated measurements into the existing scoring system will better identify patients at increased risk for complications of AP.

Tissue-resident memory T cells (TRMs) are long-lived cells poised for rapid immune responses to pathogens. This study assesses whether peritoneal CD8 T cells from patients with cirrhosis exhibit TRM-like functionalities, focusing on how inflammatory events shape phenotype and function. Peritoneal CD8 T cell subsets from patients with decompensated cirrhosis were analysed using mass cytometry, flow cytometry, RT-qPCR, single-cell RNA sequencing, in vitro culture, and cytokine profiling. Cells from 87 patients were used, of which 30 experienced spontaneous bacterial peritonitis (SBP). Soluble co-inhibitory (checkpoint) receptors were investigated in cell-free ascites from 80 patients, and TRM-activating cytokines were quantified in peritoneal macrophages. Unsupervised mass cytometry and subsequent flow cytometry validation confirmed the peritoneal abundance of CD103+ CD69+ CD8+ memory T cells in ascites compared with blood (2.2% vs. 0.4%; p <0.001). TRM-like cells, particularly the CD49a+ subset, were robust producers of interferon-γ (IFN-γ) post-T cell receptor ligation (35.1% vs. 15.3% in CD49- TRM-like cells; p <0.001), and were susceptible to bystander activation by IL-15. Single-cell RNA sequencing revealed tissue residency markers alongside transcriptional signatures of activation and exhaustion in IL-15-exposed peritoneal CD8 T cells. Peritoneal macrophages emerged as IL-15 sources during SBP (ascitic fluid concentration 18.6 pg/ml vs. 8.9 pg/ml; p <0.05), altering TRM-like cell phenotype even after inflammation had subsided. Despite the expression of co-inhibitory receptors, TRM-like cells maintained cytotoxic effector functions in a soluble checkpoint-rich environment, with PD-1/PDL-1 axis blockade not affecting their cytotoxic capacity. A subset of peritoneal CD8 T cells exhibits TRM-like traits and responds to macrophage-derived cytokines during peritoneal inflammation. TRM-like cells retain potent cytotoxic and proinflammatory responses after SBP resolution, underscoring their role in modulating peritoneal immunity and inflammation in cirrhosis. Patients with decompensated cirrhosis exhibit impaired immune responses increasing the risk of spontaneous bacterial peritonitis. This study provides insight into a subset of human peritoneal CD8 T cells in patients with decompensated cirrhosis that have a long-lived and tissue-resident phenotype capable of effectively fighting recognised pathogens within a short period with the help of IL-15 produced by activated macrophages in a bystander fashion. This knowledge has the potential to improve immunomodulatory therapies aiming to enhance peritoneal immune surveillance, and by targeting TRM-like cells and/or IL-15 signalling pathways. In addition, high concentrations of soluble immune checkpoints in ascites should be considered when applying immune checkpoint inhibitors in decompensated cirrhosis.

Purpose: Steatotic liver diseases (SLD) have become more prevalent over the last decade and are associated not only with cardiometabolic diseases but also with psychological symptoms (depression, fatigue). These symptoms are also common in post-COVID syndrome (PCS). Therefore, the aim of the study was to analyze the burden of SLD in PCS patients. Methods: We systematically screened all PCS patients from our post-COVID outpatient clinic using transient elastography, structured questionnaires for neurocognitive evaluation and blood sample analysis. Controls without PCS and without known liver diseases were also recruited and assessed with the same approach. Results: 560 PCS patients and 103 healthy controls were included. The overall prevalence of SLD was high in both cohorts (57 vs. 53%). PCS patients with SLD were more frequently male (41 vs. 24%), older (52 vs. 44 years) and had more cardiometabolic diseases (87.0 vs. 46.4%). Cognitive impairment was more related to SLD in PCS patients than in the no-SLD group (OR: 1.68, CI: 1.14–2.46, p = 0.008). The presence of SLD was related to severe COVID-19 with hospitalization (OR: 2.91, CI: 1.85–4.56, p < 0.001). Within 1 year of the follow-up, 152 of 289 patients described a resolution in PCS irrespective of the presence or absence of SLD (log-rank p = 0.96). Conclusions: SLD is associated with severe COVID-19 and cognitive dysfunction in PCS. Longitudinal studies are needed to assess the role of hepatic steatosis, development of post-acute infection regulation (e.g., SARS-CoV-2) and to differentiate between SLD-associated symptoms and PCS.