Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial.

OBJECTIVES: C-C-chemokine receptors (CCRs) are expressed on a variety of immune cells and play an important role in many immune processes, particularly leukocyte migration. Comprehensive preclinical research demonstrated CCR2/CCR5-dependent pathways as pivotal for the pathophysiology of severe COVID-19. Here we report human data on use of a chemokine receptor inhibitor in patients with COVID-19. METHODS: Interim results of a 2:1 randomised, placebo-controlled, investigator-initiated trial on the CCR2/CCR5-inhibitor Cenicriviroc (CVC) 150 mg BID orally for 28 d in hospitalised patients with moderate to severe COVID-19 are reported. The primary endpoint is the subject's responder status defined by achieving grade 1 or 2 on the 7-point ordinal scale of clinical improvement on day 15. RESULTS: Of the 30 patients randomised, 18 were assigned to receive CVC and 12 to placebo. Efficient CCR2- and CCR5 inhibition was demonstrated through CCL2 and CCL4 elevation in CVC-treated patients (485% and 80% increase on day 3 compared to the baseline, respectively). In the modified intention-to-treat population, 82.4% of patients (14/17) in the CVC group met the primary endpoint, as did 91.7% (11/12) in the placebo group (OR = 0.5, 95% CI = 0.04-3.41). One patient treated with CVC died of progressive acute respiratory distress syndrome, and the remaining had a favourable outcome. Overall, treatment with CVC was well tolerated, with most adverse events being grade I or II and resolving spontaneously. CONCLUSIONS: Our interim analysis provides proof-of-concept data on CVC for COVID-19 patients as an intervention to inhibit CCR2/CCR5. Further studies are warranted to assess its clinical efficacy.

[Functional Exams in the gastroenterology - new developments and tips for the common practice]. / Gastroenterologische Funktionsdiagnostik ­ neue Entwicklungen und Tipps für die Praxis.

The functional gastrointestinal disorders (FGIDs) have a high prevalence and are associated with high healthcare costs. The diagnosis of these diseases could be difficult and require func-tional tests such as high-resolution manometry (HRM) of the esophagus, anorectal manometry and H2-Breathtests. Due to the COVID-19 Pandemic and the fear of infections there was a marked reduction in the number of performed exams in the last months - nevertheless some exams are necessary, in order to exclude or to diagnose important and dangerous diseases like Achalasia. Goal of this article is to present some new and relevant developments in the field. The HRM of the esophagus is the diagnostic standard for Achalasia, a rare clinical condi-tion associated to dysphagia - new European guidelines suggests a safe strategy in perform-ing the pneumatic dilatation.The intestinal methanogen overgrowth (IMO) is a clinical condition caused by a high production of methane in the small intestine due to overgrowth of Methanobrevibacter smithii, this condition could be in some patients associated with irritable bowel syndrome.