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

Sexe et schistosome (écologie des interactions hôte-parasite et parasite-parasite)

Le cycle biologique du genre Schistosoma est analysé à travers les interactions hôte-parasite en fonction du sexe de l'infestation et à travers les interactions parasite-parasite sexe-dépendantes. L'analyse des interactions hôte-parasite en fonction du sexe de l'infestation révèle que les mâles schistosomes induisent une plus grande pathogénie que les femelles schistosomes aussi bien chez l'hôte mollusque que chez l'hôte vertébré. Chez l'hôte mollusque, les fonctions de nutrition, de relation et de reproduction sont plus affectées par un parasite mâle que par un parasite femelle. Chez l'hôte vertébré, la pathogénie dépend du sexe de l'hôte et du sexe du parasite. Les souris femelles sont plus affectées que les souris mâles et le parasite mâle stimule plus le système immunitaire de son hôte que le parasite femelle. Cette différence de pathogénie entre le mâle et la femelle révèle des stratégies différentes d'évolution au cours du cycle biologique des schistosomes. Les interactions parasite-parasite sont analysées aussi bien chez l'hôte mollusque que chez l'hôte vertébré. Chez l'hôte mollusque, la présence simultanée des deux sexes du parasite stimule la réussite de développement des larves infestantes émises par ce mollusque. Chez l'hôte vertébré, nous mettons en évidence des interactions intra et intersexes. Les femelles génétiquement différentes entreraient en compétition (interaction intrasexe) et feraient le choix du mâle (interaction intersexe). Ces interactions sont à rapprocher des phénomènes de sélection sexuelle qui pourraient influencer les traits de vie de ces parasites.PERPIGNAN-BU Sciences (661362101) / SudocSudocFranceF

Les Schistosomoses au Bénin (épidémiologie et écologie des interactions hôte-parasite)

Ce travail présente une étude épidémiologique et une étude des interactions hôte-parasite sur les schistosomoses au Bénin. Au plan épidémiologique, une synthèse bibliographique de l'état des travaux réalisés sur les schistosomoses dans l'espace de la Communauté Economique des Etats de l'Afrique de l'Ouest (CEDEAO) a été menée. Au Bénin, nos analyses épidémiologiques ont permis de confirmer l'existence de deux espèces de schistosomes humains : S. haematobium et S. mansoni sur les cinq signalées dans l'espace CEDEAO dans lequel le Bénin se situe (S. haematobium, S. mansoni, S. guineensis, S. bovis et S. curassoni). La prévalence générale obtenue pour S. haematobium est de 85% et celle de S. mansoni est de 30%, avec l'existence de foyers de transmission mixtes. Les prospections malacologiques ont révélé la présence au Bénin d'au moins cinq espèces de mollusques potentiellement vectrices : B. forskalii, B. globosus et B. truncatus, vectrices de S. haematobium, B. pfeifferi, vectrice de S. mansoni et I. exustus, mollusque exotique au Bénin, connu comme vecteur de S. indicum, S. spindale et S. nasale en Asie du sud-est. Nous signalons la présence de I. exustus pour la première fois au Bénin où ce mollusque semble être, pour le moment, passif dans la transmission des schistosomoses. Au plan de l'écologie des interactions mollusque-parasite, notre étude a montré que les différentes populations de S. haematobium sont différemment compatibles avec trois des quatre groupes de mollusques Bulinus : le groupe africanus, le groupe forskalii et le groupe reticulatus alors que les différentes populations de S. mansoni sont toutes également compatibles avec B. pfeifferi. L'analyse de six traits d'histoire de vie, période prépatente, prévalence, production cercarienne chez le parasite et croissance, reproduction et survie des mollusques a été abordée avec cinq populations locales de schistosomes dont trois populations de S. haematobium (Doh, Sô-Tchanhoué et Toho-Todougba) et deux populations de S. mansoni (Kpinnou et Toho-Todougba) et a révélé que si les populations de S. haematobium semblent être adaptées à un vecteur local, ce n'est pas le cas chez l'espèce S. mansoni. Au plan de l'écologie des interactions vertébré-parasite, notre étude a révélé l'existence d'un rythme d'émission cercarienne horaire particulier, de type infradien, à la fois chez S. haematobium et chez S. mansoni. L'étude anthropique réalisée au niveau d'un des foyers de transmission (Toho-Todougba) où les deux espèces sont présentes a permis de constater une parfaite synergie entre la chronobiologie cercarienne et la dynamique des activités chez l'Homme : il pourrait s'agir d'une stratégie développée par le parasite pour maintenir ses rendez-vous avec son hôte naturel vertébré.This work presents an epidemiological and an ecological study of schistosomiasis in Benin. A synthesis of the epidemiological knowledge of schistosomiasis in the space of the Economic Community of West Africa States (ECOWAS) was carried out. Furthermore, in Benin, we confirmed the existence of the two human schistosomes : S. haematobium and S. mansoni on the five existing in the ECOWAS space in which Benin is located (S. haematobium, S. mansoni, S. guineensis, S. bovis and S. curassoni). The prevalence obtained for S. haematobium was 85% and that for S. mansoni was 30%, and there was evidence for mixed human infections. We could find in Benin at least five potentially snail vector species : B. forskalii, B. globosus and B. truncatus for S. haematobium, B. pfeifferi for S. mansoni and I. exustus, an exotic snail known to be the snail vector for S. indicum, S. spindale and S. nasale in South-East Asia. I. exustus is recorded for the first time in Benin in this work and no evidence of active transmission was made. The study of the snail-schistosome interactions showed that the different S. haematobium populations were differently compatible with three of the four groups of Bulinus : the africanus group, the forskalii group and the reticulatus group and that the different S. mansoni populations were equally compatible with B. pfeifferi. The six life-history traits, parasite prepatent period, prevalence and cercarial production and snail growth, reproduction and survival were analyzed using five schistosome populations from Benin including three populations of S. haematobium (Doh, Sô-Tchanhoué and Toho-Todougba) and two populations of S. mansoni (Kpinnou and Toho-Todougba) and revealed that if the S. haematobium populations seemed to be adapted to a local vector, this was not the case for the S. mansoni populations. The study of the vertebrate-schistosome interactions revealed the existence of an infradian rhythm in the cercarial emissions of both S. haematobium and S. mansoni. The human behaviour, followed in one of the transmission sites (Toho-Todougba) where both schistosome species are present, was perfectly correlated with the schistosome chronobiology. This was interpreted in terms of adaptative strategy favouring the transmission of the parasite to its human host.PERPIGNAN-BU Sciences (661362101) / SudocSudocFranceF

Paléoparasitologie (contribution à l'étude des paléoenvironnements de sites pléistocènes et holocènes du littoral méditerranéen français)

La paléoparasitologie est la recherche d'œufs d'helminthes parasites dans des excréments ou des sédiments organiques fossilisés. Cette recherche passe par l'adaptation des techniques de la parasitologie médicale à du matériel desséché et nécessite, au préalable, une description détaillée et standardisée des coprolithes qui seront détruits pour l'analyse. Nous avons analysé 31 coprolithes et 25 échantillons de sédiments provenant de neuf sites du Bassin méditerranéen français datés du Pléistocène moyen au Moyen-Âge. L'identification, dans ces échantillons, de 23 espèces différentes de parasites, dont deux espèces probablement " fossiles ", nous a permis d'améliorer notre connaissance sur les parasitoses anciennes, d'apporter des informations sur les comportements alimentaires et sanitaires des hôtes de ces parasites et de mieux comprendre la fonction de certains vestiges archéologiques. Ce travail représente 98% des résultats d'analyses dans le Bassin méditerranéen français, toutes époques confondues, et 82% des résultats pour le Paléolithique inférieur dans le monde.PERPIGNAN-BU Lettres-Sc.humaines (661362102) / SudocSudocFranceF

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes

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