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T helper 1 (T H 1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated T H 1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection. Exposed to alternative differentiation signals, the sorted subpopulations exhibited graded levels of plasticity, particularly toward the T H 2 lineage: T-bet quantities were inversely correlated with the ability to express the T H 2 lineage-specifying transcription factor GATA-3 and T H 2 cytokines. Reprogramed T H 1 cells acquired graded mixed T H 1 + T H 2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated T H 1 cells was essential to ensure T H 1 cell stability. Thus, innate cytokine signals regulate T H 1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.

Background: Mobile applications (apps) are a resource for information on lifestyle and nutrition which are associated to improved outcomes in inflammatory arthritis., Objective: The aim of this study was to explore whether targeted lifestyle counselling via an app improves disease activity in arthritis patients., Methods: Patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA) were randomized to 12 weeks of lifestyle counselling via an app (Mida, Midaia GmbH, Germany) pertaining to a healthy Mediterranean Diet, physical activity, and mental health. Disease activity was measured with specific instruments by a blinded physician and categorized (remission, low, moderate, high). Dietary adherence was assessed by the Mediterranean Diet Adherence Screener (MEDAS). Mixed effects logistic regression adjusted to baseline disease activity, age, and sex were calculated., Results: Of 158 patients included (73% female, 53.3 ± 11.7 years), 74 were in the active counselling group (ACG). All showed improvement in low disease activity or remission. ACG patients had an odds ratio (OR) of 2.8 (95%-CI 1.1-7.2, p = 0.035), while OR in the control group was not significant OR = 2.1 (0.9-5.0, p = 0.097). The control group was less likely to reach a MEDAS >= 4 (OR = 0.16 (0.03-0.77), p = 0.02), while this was not seen in the ACG (OR = 0.54 (0.06-4.63), p = 0.6). Patients in the ACG showed a tendency towards improved adhesion to a Mediterranean Diet (MEDAS) (β = 0.35 (-0.05-0.74), p = 0.086). This tendency was not observed in the control group (β = 0.09 (-0.29-0.46), p = 0.64)., Conclusions: Individualized lifestyle and dietary counselling via app may help to improve disease control in inflammatory arthritis patients.

Introduction: Recently, diet has received considerable attention as an important factor in inflammatory arthritis. The objective of this study was to evaluate disease activity and fatigue in patients with rheumatoid arthritis and spondyloarthritis (including psoriatic arthritis) depending on their dietary preferences., Material and Methods: We retrospectively evaluated data of 774 patients collected by the Mida Rheuma App from January 2022 to December 2022. We assessed demographic parameters, major dietary patterns, and food groups (dairy products, fruits, vegetables, processed meat, meat, oily fish, white fish, and sugar) by each patient's consumption intensity. Disease activity was measured by Routine Assessment of Patient Index Data 3 (RAPID3), Patient's Global Assessment of Disease Activity (PtGADA), and Patient's Global Assessment of Pain Intensity (PPAIN). Fatigue was assessed by the Brief Fatigue Inventory (BFI). Depending on the food group, patients were divided into a high-consumption group (HCG; consuming the product 0-2 times per day/per week) and a lowconsumption group (LCG; consuming the product 3 and more times per day/per week). Patients on a specific diet which they followed before inclusion in the analysis were compared with the "eat all group" (EAG)., Results: The Mediterranean diet group had significantly lower ( p < 0.05) RAPID3, PtGADA, and PPAIN (by 9.22%, 8.98%, and 14.3%, respectively), compared with the EAG. In the processed meat HCG, RAPID3, PtGADA, PPAIN, and BFI were significantly higher (14.5%, 18.3%, 16.1%, and 11.8%, p < 0.05) vs. the LCG. The PtGADA, PPAIN, and RAPID3 were significantly lower ( p < 0.05) in the oily fish HCG vs. the LCG (18.9%, 18.1%, and 10.6%)., Conclusions: Our study results suggest that Mediterranean diet and oily fish have a potentially positive impact on patient-reported disease activity and fatigue in patients with inflammatory arthritis. In contrast, processed meat consumption has a negative effect., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Serological assays measuring antibodies against SARS-CoV-2 are key to describe the epidemiology, pathobiology or induction of immunity after infection or vaccination. Of those, multiplex assays targeting multiple antigens are especially helpful as closely related coronaviruses or other antigens can be analysed simultaneously from small sample volumes, hereby shedding light on patterns in the immune response that would otherwise remain undetected. We established a bead-based 17-plex assay detecting antibodies targeting antigens from all coronaviruses pathogenic for humans: SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV strains 229E, OC43, HKU1, and NL63. The assay was validated against five commercial serological immunoassays, a commercial surrogate virus neutralisation test, and a virus neutralisation assay, all targeting SARS-CoV-2. It was found to be highly versatile as shown by antibody detection from both serum and dried blot spots and as shown in three case studies. First, we followed seroconversion for all four endemic HCoV strains and SARS-CoV-2 in an outbreak study in day-care centres for children. Second, we were able to link a more severe clinical course to a stronger IgG response with this 17-plex-assay, which was IgG1 and IgG3 dominated. Finally, our assay was able to discriminate recent from previous SARS-CoV-2 infections by calculating the IgG/IgM ratio on the N antigen targeting antibodies. In conclusion, due to the comprehensive method comparison, thorough validation, and the proven versatility, our multiplex assay is a valuable tool for studies on coronavirus serology., (© 2023. The Author(s).)

Purpose: COViK, a prospective hospital-based multicenter case-control study in Germany, aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave., Methods: We analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates., Results: 21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12-78%), 81.5% (95% CI: 68-90%) and 95.6% (95%CI: 88-99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses., Conclusion: Three vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection., (© 2023. The Author(s).)

Background/purpose: While current guidelines recommend the use of respiratory tract specimens for the direct detection of SARS-CoV-2 infection, saliva has recently been suggested as preferred sample type for the sensitive detection of SARS-CoV-2 B.1.1.529 (Omicron). By comparing saliva collected using buccal swabs and oro-/nasopharyngeal swabs from patients hospitalized due to COVID-19, we aimed at identifying potential differences in virus detection sensitivity between these sample types., Methods: We compare the clinical diagnostic sensitivity of paired buccal swabs and combined oro-/nasopharyngeal swabs from hospitalized, symptomatic COVID-19 patients collected at median six days after symptom onset by real-time polymerase chain reaction (PCR) and antigen test., Results: Of the tested SARS-CoV-2 positive sample pairs, 55.8% were identified as SARS-CoV-2 Omicron BA.1 and 44.2% as Omicron BA.2. Real-time PCR from buccal swabs generated significantly higher quantification cycle (Cq) values compared to those from matched combined oro-/nasopharyngeal swabs and resulted in an increased number of false-negative PCR results. Reduced diagnostic sensitivity of buccal swabs by real-time PCR was observed already at day one after symptom onset. Similarly, antigen test detection rates were reduced in buccal swabs compared to combined oro-/nasopharyngeal swabs., Conclusion: Our results suggest reduced clinical diagnostic sensitivity of saliva collected using buccal swabs when compared to combined oro-/nasopharyngeal swabs in the detection of SARS-CoV-2 Omicron in symptomatic individuals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

We included 852 patients in a prospectively recruiting multicenter matched case-control study in Germany to assess vaccine effectiveness (VE) in preventing COVID-19-associated hospitalization during the Delta-variant dominance. The two-dose VE was 89 % (95 % CI 84-93 %) overall, 79 % in patients with more than two comorbidities and 77 % in adults aged 60-75 years. A third dose increased the VE to more than 93 % in all patient-subgroups., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. G. received payment/honoraria from Astra Zeneca, Boehringer Ingelheim, Roche Pharma and Berlin Chemie, this had no influence on this work; all other authors reported no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

EULAR highlighted the essential role of digital health in increasing self-management and improving clinical outcomes in patients with arthritis. The objective of this study was to evaluate the efficacy and safety of the digital health application (DHA) in patients with inflammatory arthritis. We assessed demographic parameters, treatment regimen, disease activity, and other patient-reported outcomes at baseline and after 4 weeks of DHA use added to standard care treatment. Of 17 patients, who completed the study, 7 (41.2%) patients were male, ranging from 19 to 63 (40.5 ± 12.2) years. No significant change in antirheumatic treatment was observed during the study. Statistically significant improvements (p < 0.05) were noted for health-related quality of life (increase in Physical Component Summary of Short Form-36 (SF-36) by 23.6%) and disease activity (decrease of Clinical Disease Activity Index and Simple Disease Activity Index by 38.4% and 39.9%, respectively). Clinically significant improvement was demonstrated for SF-36 Total Score (+ 14.4%), disease activity (Rheumatoid Arthritis Disease Activity Index- 5 to 15.9%), and depression (Patient Health Questionnaire- 9 to 13.5%). None of the efficacy parameters showed negative trends. No adverse events were reported throughout the study. The usability level was high i.e., the mean mHealth Application Usability Questionnaire Score of 5.96 (max.: 7.0) demonstrated a high level of application usability. This suggests that using a personalized disease management program based on DHA significantly improves several measures of patient-reported outcomes and disease activity in patients with inflammatory arthritis in a timely manner. These findings highlight the potential of complementary digital therapy in patients with inflammatory arthritis., (© 2022. The Author(s).)

Vaccines against COVID-19 have been available in Germany since December 2020. At the Robert Koch Institute (RKI), the Immunization Unit is responsible for monitoring vaccination coverage and assessment of vaccine effectiveness. This article provides an overview of the respective reporting structures, vaccination databases, and epidemiological studies established by the Immunization Unit during the COVID-19 pandemic. We describe the COVID-19 Digital Vaccination Coverage Monitoring (DIM), which provides daily updates on vaccination coverage by age group. We next describe how, based on the DIM data and COVID-19 case data, the assessment of vaccine effectiveness against different clinical endpoints (hospitalization, intensive care, death) is performed. While this method is used for a preliminary estimate of vaccine efficacy, population-based nonrandomized studies are able to provide more precise and detailed estimates under "real-world" conditions. In this context, we describe the hospital-based case-control study COViK, which is being conducted in collaboration with the Paul Ehrlich Institute (PEI). We discuss strengths and limitations of the abovementioned structures and tools. Finally, we provide an outlook on future challenges that may arise during the ongoing pandemic and during the transition phase into an endemic situation., (© 2022. The Author(s).)

Selective differentiation of CD4+ T helper (Th) cells into specialized subsets such as Th1 and Th2 cells is a key element of the adaptive immune system driving appropriate immune responses. Besides those canonical Th-cell lineages, hybrid phenotypes such as Th1/2 cells arise in vivo , and their generation could be reproduced in vitro . While master-regulator transcription factors like T-bet for Th1 and GATA-3 for Th2 cells drive and maintain differentiation into the canonical lineages, the transcriptional architecture of hybrid phenotypes is less well understood. In particular, it has remained unclear whether a hybrid phenotype implies a mixture of the effects of several canonical lineages for each gene, or rather a bimodal behavior across genes. Th-cell differentiation is a dynamic process in which the regulatory factors are modulated over time, but longitudinal studies of Th-cell differentiation are sparse. Here, we present a dynamic transcriptome analysis following Th-cell differentiation into Th1, Th2, and Th1/2 hybrid cells at 3-h time intervals in the first hours after stimulation. We identified an early bifurcation point in gene expression programs, and we found that only a minority of ~20% of Th cell-specific genes showed mixed effects from both Th1 and Th2 cells on Th1/2 hybrid cells. While most genes followed either Th1- or Th2-cell gene expression, another fraction of ~20% of genes followed a Th1 and Th2 cell-independent transcriptional program associated with the transcription factors STAT1 and STAT4. Overall, our results emphasize the key role of high-resolution longitudinal data for the characterization of cellular phenotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Burt, Peine, Peine, Borek, Serve, Floßdorf, Hegazy, Höfer, Löhning and Thurley.)