In Schistosoma mansoni-infected mice, gastrointestinal transit was measured in vivo and the neuromuscular function of longitudinal muscle strips of inflamed ileum and noninflamed gastric fundus was assessed in vitro. Eight weeks after infection, the ileal wall was acutely inflamed, as shown by a mucosal inflammatory infiltrate, leading to an increase in mucosal thickness, in myeloperoxidase (MPO) activity, and in interleukin (IL)-1beta production. At that time, both gastrointestinal transit and in vitro ileal contractility were normal. Twelve weeks after infection, chronic granulomatous inflammation led to proliferation of the muscle layer and to a further increase in MPO activity, whereas IL-1beta production normalized. Gastrointestinal transit was decreased, whereas in vitro ileal contractility was increased irrespective of the contractile stimulus. In vitro incubation with IL-1beta (10 ng/ml for 60 min) significantly increased ileal contractility only at 8 wk after infection. Indomethacin, tetrodotoxin, and atropine had no differential effect on ileal contractility in controls and infected mice. In vitro contractility of noninflamed gastric fundus was normal both 8 and 12 wk after infection. We conclude that intestinal schistosomiasis 8 wk after infection is associated only with structural changes of the ileum, whereas 12 wk after infection, both structural and functional changes are present. These changes are characterized by increased ileal wall thickness, decreased gastrointestinal transit, and increased smooth muscle contractility restricted to the inflamed gut segment.

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BACKGROUND. SARS-CoV-2 infection induces mucin overexpression further promoting disease. As mucins are critical components of the innate immunity, unravelling their expression profiles that dictate the course of disease could greatly enhance our understanding and management of COVID-19. METHODS.Using validated RT-PCR assays, we assessed mucin mRNA expression in the blood of symptomatic COVID-19 patients compared to symptomatic non-COVID-19 patients and healthy controls and correlated the data to clinical outcome parameters. Additionally, we analyzed mucin expression in mucus and lung tissue from COVID-19 patients and investigated the effect of drugs for COVID-19 treatment on SARS-CoV-2-induced mucin expression in pulmonary epithelial cells. RESULTS.We identified a dynamic blood mucin mRNA signature that clearly segregates symptomatic COVID-19 from non-COVID-19 patients based on expression of MUC1, MUC2, MUC4, MUC6, MUC13, MUC16 and MUC20 (AUCROC of 91.8 %; sensitivity and specificity of respectively 90.6% and 93.3%); and that discriminates between mild and critical COVID-19 based on the expression of MUC16, MUC20 and MUC21 (AUCROC of 89.1 %; sensitivity and specificity of respectively 90.0% and 85.7%). Differences in the transcriptional landscape of mucins in critical cases compared to mild cases even identify associations with COVID-19 symptoms, respiratory support, organ failure, secondary infections and mortality. Furthermore, we identified different mucins in mucus and lung tissue of critically ill COVID-19 patients and showed the ability of baricitinib, tocilizumab, favipiravir and remdesivir to suppress expression of the SARS-CoV-2-induced mucins. CONCLUSION.This multifaceted blood mucin mRNA signature shows the potential role of mucin profiling in diagnosing, estimating severity and guiding treatment options in COVID-19 patients.

In this study of the humoral immune response after the SARS-CoV-2 mRNA vaccination, low seroconversion rates were noted in both kidney transplant recipients and dialysis patients after first dose administration. While in DP the seroconversion rate levelled up to 92.8% after a second dose of SARS-CoV-2 mRNA vaccination, KTR stayed behind with a seroconversion rate of 62.4%. Futhermore, vaccination with the mRNA-1273 vaccine (Moderna) resulted in both higher seroconversion rates and mean log-transformed antibody titer concentrations compared to BNT162b2 (Pfizer). Main textWith the roll-out of COVID-19 vaccines, it has become clear that vaccinating the majority of the population worldwide will be the most important element to control and manage the ongoing COVID-19 pandemic. Several reports have shown diminished immunogenicity of SARS-CoV-2 vaccines in both kidney transplant recipients (KTR) and dialysis patients (DP), as evidenced in a recent narrative review [1]. Furthermore, two recent articles have included comparisons between the immunogenicity of the mRNA-1273 (Moderna) versus the BNT162b2 (Pfizer) vaccine in these populations [2, 3]. Boyarsky et al. studied a cohort of solid organ transplant recipients, including KTR, and reported lower seroconversion rates after receiving the Pfizer vaccine [3]. Stumpf et al. also described lower seroconversion rates in KTR and DP receiving the Pfizer vaccine [2]. However, none of these articles reported the titers of anti-SARS-CoV-2 antibodies. Therefore, we here compared the immunogenicity of