Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic. Cytokine release syndrome occurring in a minority of SARS-CoV-2 infections is associated with severe disease and high mortality. We profiled the composition, activation, and proliferation of T cells in 20 patients with severe or critical COVID-19 and 40 matched healthy controls by flow cytometry. Unsupervised hierarchical cluster analysis based on 18 T cell subsets resulted in separation of healthy controls and COVID-19 patients. Compared to healthy controls, patients suffering from severe and critical COVID-19 had increased frequencies of activated and proliferating CD38+Ki67+ CD4+ and CD8+ T cells, suggesting active antiviral T cell defense. Frequencies of CD38+Ki67+ Th1 and CD4+ cells correlated negatively with plasma IL-6. Thus, our data suggest that patients suffering from COVID-19 have a distinct T cell composition that is potentially modulated by IL-6. Key Points Distribution of T cell subsets is altered in COVID-19 compared to healthy subjects. Cytotoxic and Th1 cells are activated and proliferating in COVID-19. Activated and proliferating Th1 cells negatively correlate with plasma IL-6.
Soluble urokinase plasminogen activator receptors (suPARs) are a biomarker for inflammatory diseases. This study aims to investigate its diagnostic properties regarding periprosthetic joint infections (PJI). This retrospective cohort study included adult patients who underwent joint puncture for suspected PJI. The presence of PJI was determined according to the criteria of the European Bone and Joint Infection Society (EBJIS). Laboratory study analyses included the determination of white blood cells (WBC) in whole blood, C-reactive protein (CRP) in blood plasma, and suPAR in both blood plasma and synovial fluid. Appropriate diagnostic cut-off values were identified utilizing Youden’s J, and their diagnostic performance was determined by calculating the positive (PPV) and negative predictive value (NPV) for each marker. Sixty-seven cases were included in the final analysis. Forty-three samples (64%) were identified as periprosthetic joint infection (PJI) and twenty-four specimen (36%) were PJI negative cases. The PPV and NPV were 0.80 and 0.70 for synovial suPAR, 0.86 and 0.55 for CRP, 0.84 and 0.31 for WBC and 1.00 and 0.31 for plasma suPAR. Synovial suPAR showed a solid diagnostic performance in this study and has the potential to be an alternative or complementary biomarker for PJI. Further investigations in larger patient collectives are indicated.
Objectives: To evaluate the clinical efficacy and safety of a multispecies probiotic in patients with PsA in moderate disease activity. Methods: In this single-centre, randomized, double-blind, placebo-controlled trial (RCT), 66 PsA patients with moderate disease activity (Psoriatic Arthritis Disease Activity Score [PASDAS] > 3.2 to <5.4) on stable immunomodulatory therapy were randomized 1:1 to receive either a multispecies (Lactobacillus, Bifidobacterium) probiotic or placebo for 12 weeks. The primary outcome was treatment response at week 12, defined as achieving low disease activity or remission (PASDAS ≤3.2) without treatment change. Secondary outcomes included gut permeability markers, immune cell and microbiome composition. Analyses were conducted per a modified intention-to-treat (only complete cases for primary outcome), with sensitivity analyses using multiple imputation, per-protocol datasets and qPCR-based detection of the probiotic strains in stool (adherence). Results: Fifty-six participants were included in the main analysis. Thirteen (43%) participants in the probiotic group and 17 (65%) in the placebo group achieved the primary outcome (P = 0.167). The corresponding odds ratio was 0.4 (95% CI 0.13–1.18). Patient-reported pain and global assessment were the main PASDAS components improving over time, with no between-group differences. No differences were observed in secondary clinical outcomes, gut permeability markers (zonulin, calprotectin, alpha-1-antitrypsin), immune cell profiles or stool microbiome composition between the groups at week 12. No serious adverse events related to the study product were reported. Conclusion: In this first RCT investigating probiotic supplementation in PsA, probiotic treatment did not show superiority over placebo in achieving treatment response, or altering gut microbiome, or permeability.