The specific metabolome profiling of patients infected by SARS-COV-2 supports the key role of tryptophan-nicotinamide pathway and cytosine metabolism.

The biological mechanisms involved in SARS-CoV-2 infection are only partially understood. Thus we explored the plasma metabolome of patients infected with SARS-CoV-2 to search for diagnostic and/or prognostic biomarkers and to improve the knowledge of metabolic disturbance in this infection. We analyzed the plasma metabolome of 55 patients infected with SARS-CoV-2 and 45 controls by LC-HRMS at the time of viral diagnosis (D0). We first evaluated the ability to predict the diagnosis from the metabotype at D0 in an independent population. Next, we assessed the feasibility of predicting the disease evolution at the 7th and 15th day. Plasma metabolome allowed us to generate a discriminant multivariate model to predict the diagnosis of SARS-CoV-2 in an independent population (accuracy > 74%, sensitivity, specificity > 75%). We identified the role of the cytosine and tryptophan-nicotinamide pathways in this discrimination. However, metabolomic exploration modestly explained the disease evolution. Here, we present the first metabolomic study in SARS-CoV-2 patients which showed a high reliable prediction of early diagnosis. We have highlighted the role of the tryptophan-nicotinamide pathway clearly linked to inflammatory signals and microbiota, and the involvement of cytosine, previously described as a coordinator of cell metabolism in SARS-CoV-2. These findings could open new therapeutic perspectives as indirect targets.

Epidemiological trends for hospital admissions for acute rotavirus gastroenteritis in Belgium following the introduction of routine rotavirus vaccination and the subsequent switch from lyophilized to liquid formulation of Rotarix™.

This study describes epidemiological trends for acute rotavirus gastroenteritis (RVGE) in Belgium in children aged ⩽5 years during the period June 2007 to May 2014 after the introduction of routine rotavirus (RV) vaccination. This period encompassed the switch from lyophilized to the liquid formulation of Rotarix™ (GlaxoSmithKline, Belgium) in August 2011. Uptake of RV vaccine remained consistently high throughout the study period with Rotarix the brand most often used. RV was present in 9% (1139/12 511) of hospitalized cases with acute gastroenteritis included in the study. Epidemiological trends for hospital admissions for RVGE remained consistent throughout the study period, with no evidence of any change associated with the switch from lyophilized to liquid formulation of Rotarix. This suggests both formulations perform similarly, with the liquid formulation not inferior regarding ability to reduce hospital admissions for acute RVGE in children aged ⩽5 years. A strong seasonal effect was observed with most RVGE occurring in the winter months but with some variability in intensity, with highest incidence found in those aged 6-24 months. The main observation was the decreased number of hospital admissions for RVGE in Belgium that occurred during winter 2013/2014.

Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers.

BACKGROUND: Rare disease patients and caregivers face uncommon, serious, debilitating conditions often characterised by poor prognosis and limited treatment options. This study aimed to explore what they consider of value when choosing between hypothetical therapeutic options and to quantify both their benefit-risk preferences and the influence of disease context. METHODS: A mixed-methods survey with patients and caregivers was conducted in the United Kingdom across a range of rare diseases. Discrete-choice experiments that compared hypothetical treatment profiles of benefits and risks were used to measure respondent preferences across a set of seven attributes related to health outcomes, safety, and process of care. Bespoke questions on current disease management and the joint use of the 12-item WHODAS 2.0 questionnaire and of two Likert scales capturing self- and proxy-assessed disease-induced threat to life and impairment were implemented to describe disease context. Additionally, qualitative insights on the definitions of value and risk were collected from respondents. RESULTS: Final study sample included 721 patients and 152 informal caregivers, across 52 rare diseases. When choosing between hypothetical novel treatments for rare diseases, respondents attributed most importance to drug response, risk of serious side effects, and the ability to conduct usual activities while on treatment. In contrast, attributes related to treatment modalities were the least important. Respondents expressed a willingness to accept risks in hopes of finding some benefit, such as a higher chance of drug response or greater health improvement potential. Increasing disease severity, impairment or disability, and the lack of effective therapeutic options were shown to raise significantly the willingness to gain benefit through increased risk. CONCLUSIONS: This is the first study performing a quantitative discrete choice experiment amongst patients and caregivers across 52 rare conditions. It enables a more detailed understanding of the relationship between disease context, treatment attributes and the degree of risk respondents are willing to take to gain a specific degree of benefit. Researchers of novel therapeutics for rare diseases should be encouraged to invest in preference elicitation studies to generate rigorous patient evidence and specific regulatory guidance should be issued to acknowledge their importance and their use in marketing authorisations.