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Introduction Corticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients’ response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated with adults with sepsis responsiveness to corticosteroids.Methods and analysis RECORDS, a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial, will randomly assign to a biomarker stratum 1800 adults with community-acquired pneumonia, vasopressor-dependent sepsis, septic shock or acute respiratory distress syndrome. In each stratum, patients will be randomly assigned to receive a 7-day course of hydrocortisone and fludrocortisone or their placebos. Patients with COVID-19 will be treated with a 10-day standard course of dexamethasone and randomised to fludrocortisone or its placebo. Primary outcome will be 90-day death or persistent organ dysfunction. Large simulation study will be performed across a range of plausible scenarios to foresee power to detect a 5%–10% absolute difference with corticosteroids. We will assess subset-by-treatment interaction by estimating in a Bayesian framework two quantities: (1) measure of influence, relying on the value of the estimation of corticosteroids’ effect in each subset, and (2) measure of interaction.Ethics and dissemination The protocol was approved by the Ethics Committee (Comité de Protection des Personnes, Dijon, France), on 6 April 2020. Trial results will be disseminated at scientific conferences and results will be published in peer-reviewed journals.Trial registration number ClinicalTrials.gov Registry (NCT04280497).

Background: Early diagnosis of coronavirus disease 2019 (COVID-19) is of the utmost importance but remains challenging. The objective of the current study was to characterize exhaled breath from mechanically ventilated adults with COVID-19. Methods: In this prospective observational study, we used real-time, online, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of expired air from adults undergoing invasive mechanical ventilation in the intensive care unit due to severe COVID-19 or non-COVID-19 acute respiratory distress syndrome (ARDS). Findings: Between March 25th and June 25th, 2020, we included 40 patients with ARDS, of whom 28 had proven COVID-19. In a multivariate analysis, we identified a characteristic breathprint for COVID-19. We could differentiate between COVID-19 and non-COVID-19 ARDS with accuracy of 93% (sensitivity: 90%, specificity: 94%, area under the receiver operating characteristic curve: 0·94-0·98, after cross-validation). The four most prominent volatile compounds in COVID-19 patients were methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal. Interpretation: The real-time, non-invasive detection of methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal in exhaled breath may identify ARDS patients with COVID-19. Funding: The study was funded by Agence Nationale de la Recherche (SoftwAiR, ANR-18-CE45-0017 and RHU4 RECORDS, Programme d'Investissements d'Avenir, ANR-18-RHUS-0004), Région Île de France (SESAME 2016), and Fondation Foch.

The neural representation of a moving target undergoes a spatiotemporal “diffusion” while the associated retinal activity propagates toward the motor centers and recruits the appropriate muscles for its interception in the external world. Indeed, the divergent projections within the visual system and the transmissions of signals through multiple relays, with diverse conduction velocities and integration times, lead to activities that are spatially and temporally distributed across several brain regions. In spite of this neural “blurring”, accurate saccadic eye movements can be made to bring the image of a moving target onto the fovea. Such a performance indicates that the brain is able to rapidly estimate the current spatiotemporal coordinates of the target, at least at the time of saccade landing. We tested in the monkey the robustness of this estimate when a change in eye position and a delay are experimentally added before the animal launches a saccade toward a moving target and in the absence of visual feedback. These spatiotemporal perturbations were induced by a brief microstimulation in the deep superior colliculus. The results show that the interceptive saccades can remain accurate and relatively independent of the time taken to react and to foveate the target. We propose that the brain builds an estimate of the expected and current spatiotemporal (hic-et-nunc) coordinates of the target and that this signal feeds the same local feedback loop as the mechanism proposed for guiding saccades toward a stationary target (Fleuriet and Goffart, 2012 Journal of Neuroscience 32 452–461).