ACTIV-3/TICO Study Group* Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

No abstract

BackgroundTwo years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited.ObjectivesTo measure the predictive performance of currently used clinical laboratory tests alone or combined with clinical variables and explore the predictive power of immunological tests adequate for clinical laboratories. Methods: Data from 2,600 COVID-19 patients of the first wave of the pandemic in the Barcelona area (exploratory cohort of 1,579, validation cohorts of 598 and 423 patients) including clinical parameters and laboratory tests were retrospectively collected. 28-day survival and maximal severity were the main outcomes considered in the multiparametric classical and machine learning statistical analysis. A pilot study was conducted in two subgroups (n=74 and n=41) measuring 17 cytokines and 27 lymphocyte phenotypes respectively.Findings1) Despite a strong association of clinical and laboratory variables with the outcomes in classical pairwise analysis, the contribution of laboratory tests to the combined prediction power was limited by redundancy. Laboratory variables reflected only two types of processes: inflammation and organ damage but none reflected the immune response, one major determinant of prognosis. 2) Eight of the thirty variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the combined statistical predictive power. 3) The interpretation of clinical and laboratory variables was moderately improved by grouping them in two categories i.e., inflammation related biomarkers and organ damage related biomarkers; Age and organ damage-related biomarker tests were the best predictors of survival, and inflammatory-related ones were the best predictors of severity. 4) The pilot study identified immunological tests (CXCL10, IL-6, IL-1RA and CCL2), that performed better than most currently used laboratory tests.ConclusionsLaboratory tests for clinical management of COVID 19 patients are valuable but limited predictors due to redundancy; this limitation could be overcome by adding immunological tests with independent predictive power. Understanding the limitations of tests in use would improve their interpretation and simplify clinical management but a systematic search for better immunological biomarkers is urgent and feasible.

Background Prolonged or recurrent gastrointestinal symptoms may persist after acute traveller’s diarrhoea, even after adequate treatment of the primary cause. This study aims to describe the epidemiological, clinical, and microbiological characteristics of patients with post-infectious irritable bowel syndrome after returning from tropical or subtropical areas. Methods We conducted a retrospective study of patients presenting between 2009 and 2018 at the International Health referral center in Barcelona with persistent gastrointestinal symptoms following a diagnosis of traveller’s diarrhoea. Post-infectious irritable bowel syndrome was defined as the presence of persistent or recurrent gastrointestinal manifestations for at least six months after the diagnosis of traveller’s diarrhoea, a negative stool culture for bacterial pathogens, and a negative ova and parasite exam after targeted treatment. Epidemiological, clinical, and microbiological variables were collected. Results We identified 669 travellers with a diagnosis of traveller’s diarrhoea. Sixty-eight (10.2%) of these travellers, mean age 33 years and 36 (52.9%) women, developed post-infectious irritable bowel syndrome. The most frequently visited geographical areas were Latin America (29.4%) and the Middle East (17.6%), with a median trip duration of 30 days (IQR 14–96). A microbiological diagnosis of traveller’s diarrhoea was made in 32 of these 68 (47%) patients, 24 (75%) of whom had a parasitic infection, Giardia duodenalis being the most commonly detected parasite (n = 20, 83.3%). The symptoms persisted for a mean of 15 months after diagnosis and treatment of traveller’s diarrhoea. The multivariate analysis revealed that parasitic infections were independent risk factors for post-infectious irritable bowel syndrome (OR 3.0, 95%CI 1.2–7.8). Pre-travel counselling reduced the risk of post-infectious irritable bowel syndrome (OR 0.4, 95%CI 0.2–0.9). Conclusions In our cohort, almost 10% of patients with travellers’ diarrhoea developed persistent symptoms compatible with post-infectious irritable bowel syndrome. Parasitic infections, mainly giardiasis, seem to be associated with post-infectious irritable bowel syndrome.