COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

NMR Using Solution Flow Circuit and Inductively-Coupled Microcoils

International audienceInvestigation of systems in evolution such as chemical reactions via NMR can be rendered com-fortable if the intrinsic lack of sensitivity of this technique is circumvented and provided that quantitative data are obtained. Here we present an integrated device based on a 3D-printed mini bubble-pump associated with fluidics and micro-detection that overcomes the sensitivity problems inherent to slow return of magnetization to equilibrium in liquid-state NMR. The use of a closed-loop circuit of the solution near the NMR magnetic center presents two main advantages: pre-polarization is achieved for the whole solution volume, this volume can be reduced to tens of microliters. This device is installable into every commercial liquid probehead without modification; it is easily inserted from the top of the NMR magnet. A gas flow driven by a programmable syringe pump actuates a mini bubble-pump which leads to circulation of the liquid sample. A part of the solution circuit crosses the NMR detection region consisting of a micro-solenoid inductively coupled to the coil of the commercial probehead. In order to optimize this coupling a rod fixed on the upper part of the insert and ended by a Vernier placed on top of the magnet enables angular positioning of the micro-coil. The two resonance frequencies created by the coupling allow one to observe nuclei inaccessible with the host probe alone, or to study two different nuclei with the optimized detection allowed by the micro coil. To further increase the signal-to-noise ratio, this system can also be used to effi-ciently dispense gaseous species such as hyperpolarized xenon and parahydrogen to the solution. The performances of this device, in particular with cryoprobes, will be presented

Inductive Coupling and Flow for Increased NMR Sensitivity

International audienceA device is proposed to enhance the NMR sensitivity of slowly-relaxing nuclei, taking advantage of a controlled solution flow within a microfluidic circuit and micro-sized NMR detection. At the difference of our previous work (Carret at al., Anal. Chem. 2017, 89 (5), 2995–3000), this set-up can be easily installed on any commercial NMR probehead as it uses induction between the commercial antenna and the micro-coil. Such a system leads to a significant gain in sensitivity per time unit for slowly relaxing nuclei while preserving the capabilities of the host probehead

Enhancing NMR of non-relaxing species using a controlled flow motion and a miniaturized circuit

International audienceIn this Article we show that circulation of the sample in a closed-loop circuit combined to micro sized detection can lead to a significant signal NMR enhancement. We present an optimized NMR device based on a mini bubble-pump associated to fluidics and microdetection that can be installed on a commercial NMR spectrometer. In addition to a significant signal enhancement for slowly relaxing nuclei, we show that it enables more precise and frequent monitoring of chemical reactions. An additional modification leads to a stopped-flow system very efficient for instance for 2D NMR experiments with long mixing times

Following the growth of Saccharomyces Cerevisiae in standard culture conditions using hyperpolarized 129^{129}Xe NMR

International audienceXenon has several interesting properties for the NMR study of biological cells: 1) its nuclear polarization can beboosted via optical pumping, which increases the detection sensitivity by several orders of magnitude. 2) It is nontoxicand soluble in biologic medium and crosses the plasma membrane while keeping its polarization. 3) It has a wide rangeof chemical shift which makes its NMR signature sensitive to fine cell changes. In particular with cell suspensions twodistinct signals are observed on the $^{129}$Xe NMR spectrum, corresponding to xenon in the bulk and xenon inside thecells. This has led to promising applications, such as the discrimination of cells sensitive and resistant to chemotherapy.In this work, we studied Saccharomyces Cerevisiae cells at different times of a culture via hyperpolarized $^{129}$Xe NMR(xenon was hyperpolarized using our home made optical pumping setup) and controlled the number of cells by themeasure of the optical density at 600 nm. For each time stage of the yeast culture, a sample was withdrawn and afterhyperpolarized xenon addition, the corresponding $^{129}$Xe spectra were analyzed in a 11.7 Tesla spectrometer: thechemical shift splitting, the in-out exchange rate and the proportion of xenon inside the cells were extracted andcompared with classical analyses using optical density. The evolution of the spectral signature of $^{129}$Xe in S. Cerevisae isdependent of the culture time as presented in the figure. Hypotheses of explanations will be presented.In parallel, new methodologies, compatible with narrow-bore NMR spectrometers, were developed to allow the in situ follow-up of cell cultures by NMR, using microfluidic system and micro-NMR detection. Surface treatment such as parylene coating was shown to increase biocompatibilit

Inductively-Coupled Microcoils and Solution Flow for Increased NMR Sensitivity

International audienceInductively-Coupled Microcoils and Solution Flow for Increased NMR SensitivityGuillaume Carret, Thomas Berthelot, Céline Boutin, Patrick BerthaultNIMBE, CEA, CNRS, Paris-Saclay University, CEA Saclay, 91191 Gif-sur-Yvette, FranceTo circumvent the sensitivity problems inherent to slow return of magnetization to equilibrium in liquid-state NMR we present a 3D-printed NMR device based on a mini bubble-pump associated with fluidics and micro-detection that can be installed in every commercial liquid-state NMR probehead.It is based on the use of a closed-loop circuit ofthe solution near the NMR magnetic center, which presents two main advantages: i) pre-polarization is achieved for the whole solution volume, ii) this volume can be reduced to tens of microliters

Use of dissolved hyperpolarized species in NMR: practical considerations

International audienceHyperpolarization techniques that can transiently boost nuclear spin polarization are generally carried out at low temperature-as in the case of dynamic nuclear polarization-or at high temperature in the gaseous state-as in the case of optically pumped noble gases. This review aims at describing the various issues and challenges that have been encountered during dissolution of hyperpolarized species, and solutions to these problems that have been or are currently proposed in the literature. During the transport of molecules from the polarizer to the NMR detection region, and when the hyperpolarized species or a precursor of hyperpolarization (e.g. parahydrogen) is introduced into the solution of interest, several obstacles need to be overcome to keep a high level of final magnetization. The choice of the magnetic field, the design of the dissolution setup, and ways to isolate hyperpolarized compounds from relaxation agents will be presented. Due to the non-equilibrium character of the hyperpolarization, new NMR pulse sequences that perform better than the classical ones will be described. Finally, three applications in the field of biology will be briefly mentioned

New developments related to fast and multiplexed detection of 129Xe NMR biosensor

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Dernières avancées sur l'utilisation du xénon polarisé comme biosonde

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Dernières avancées sur l'utilisation du xénon polarisé comme biosonde

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