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

Numerical modelling of the impact of magnetic geometry on tokamaks edge plasmas

Ce travail de thèse a montré que, dans une configuration limiteur, l’élongation des surfaces magnétiques a un effet stabilisant vis-à-vis de la turbulence dans le plasma de bord, ce qui conduit à une diminution de la largeur du plasma de bord quand l’élongation augmente. En ce qui concerne la triangularité, cette thèse a montré que ses effets sur le plasma de bord étaient plus faibles que ceux de l’élongation. Un travail théorique sur un modèle simplifié d'interchange a permis de comprendre ces tendances. Ces travaux ont également mis en lumière l'importance de la variabilité spatiale du champ magnétique sur la taille poloïdale des structures turbulentes et donc sur les flux turbulents radiaux qui en découlent. Dans un second temps, l’étude d’une configuration divertor à un point X nous a permis de voir que la variabilité spatiale du champ magnétique était telle qu'elle pourrait être une des causes du renforcement du caractère ballonné côté faible champ de la turbulence en géométrie divertor. Toujours en géométrie divertor, cette thèse a également montré que davantage de chaleur était déposée sur le matériau interne par rapport au matériau externe lorsque le champ magnétique toroïdal est orienté dans le sens direct (= dérive magnétique des ions vers le point X). Cela peut s'expliquer par l'existence d'une circulation importante de plasma du côté faible champ vers le côté fort champ au niveau du point X que l’on a observée dans cette configuration. Enfin, on a pu confirmer qu’une manière d’améliorer cette répartition des flux de chaleur sur les parois consiste à faire coïncider parfaitement deux points X (= snowflake idéal proposée en 2007 par Ryutov et Soukhanovski)This phD work has shown that, in a limiter configuration, the elongation of magnetic surfaces has a stabilizing effect with respect to the edge plasma turbulence. This leads to a reduction of the edge plasma width when the elongation increases. Regarding triangularity, this phD work revealed that its effects on the edge plasma were weaker than those of elongation. A better understanding of these trends has been possible thanks to a theoretical work on a simplified interchange model. This work has also revealed the importance of the magnetic field spatial variability on the poloidal size of turbulent structures and therefore on the radial turbulent fluxes. In a second step, the study of a divertor configuration with one X point has shown that the the magnetic field spatial variability was so important that it could be one of the reasons that explain the enhancement of the low field side ballooned nature of edge plasma turbulence in a divertor geometry. Still concerning the divertor geometry, this phD also revealed that the internal material receives more heat compared to the external material when the toroidal magnetic field is oriented in the direct direction (= magnetic drift of the ions pointing towards the X point). A possible explanation of this observation is the existence of a significant plasma circulation from the low field side to the high field side at the X point that we observed in this configuration. Finally, we were able to confirm that one way to improve this heat flux distribution on the walls was to merge two X points perfectly (= ideal snowflake proposed in 2007 by Ryutov and Sukhanovsky

Influence of Toroidal Flow on Stationary Density of Collisionless Plasmas

International audienceStarting from the given passive particle equilibrium particle cylindrical profiles, we built self-consistent stationary conditions of the Maxwell-Vlasov equation at thermodynamic equilibrium with non-flat density profiles. The solutions to the obtained equations are then discussed. It appears that the presence of an azimuthal (poloidal) flow in the plasma can ensure radial confinement, while the presence of a longitudinal (toroidal) flow can enhance greatly the confinement. Moreover in the global physically reasonable situation, we find that no unstable point can emerge in the effective integrable Hamiltonian of the individual particles, hinting at some stability of the confinement when considering a toroidal geometry in the large aspect ratio limit

Self-generated reversed radial electric field in 3D global flux-driven fluid edge plasma turbulence simulations

International audienc

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities

Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry

Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs). Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality. Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions. Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51). Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Background: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death

The value of open-source clinical science in pandemic response: lessons from ISARIC

International audienc

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use