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Dengue and coronavirus disease 2019 (COVID-19) may share clinical and laboratory features. Reunion Island is a French overseas department located in the Indian Ocean with a population of more than 850,000 inhabitants. Due to its tropical climate, Reunion Island is at risk of arbovirus outbreaks. An increase in the number of dengue cases has been reported on the island since the beginning of 2018, with 3 different serotypes circulating mostly in austral summer. According to the last epidemiological report of March 30, 2020 from Santé Publique France, 3,144 new cases of dengue have been diagnosed since the beginning of 2020 in Reunion Island [1]. On March 2020, the first COVID-19 cases were imported to the island from metropolitan France by airplane. We report the case of an 18-year-old male living in Reunion Island, with no relevant past medical history except occasional migraines. Our patient travelled back from Strasbourg (initial French epicenter of COVID-19) to Reunion Island on March 18, 2020. After his arrival, he returned to his parents' home, respected national confinement guidelines, and only went shopping once. The onset of symptoms occurred on April 3, with fever (39˚C), asthenia, anorexia, and headache. On April 4, he tested positive in the emergency department for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by reverse transcription (RT)-PCR (E gene, RdRP gene, and N gene positive), the causative virus of COVID-19. He was discharged from the emergency room after diagnosis. On April 5, an itchy erythema rash appeared. He came back to the hospital on April 7 for persistent fever (38.7˚C), arthromyalgia, dyspnea with polypnea (respiratory rate of 24 breaths per minute), and itchy maculopapular rash. The dengue rapid test was positive (NS1 antigen+) in the emergency department. Therefore, he was hospitalized the same day in the COVID-19 unit of St Denis University Hospital Center. The physical examination revealed a body temperature of 38˚C, blood pressure of 112/63 mmHg, pulse of 63 beats per minute, and oxygen saturation of 99% in ambient air. He had dry cough (since February) and no chest pain. Pulmonary auscultation was normal. He had no hematuria. He described retro-orbital eye pain and mild photophobia, with anorexia, nausea, and vomiting. He had infracentimetric cervical lymphadenopathies. Skin examination showed a roseoliform maculopapular exanthema of the trunk, limbs, and face, which rapidly evolved into a scarlatiniform-like rash. There were no real intervals of healthy skin but rounded islands of sparing ("white islands in a sea of red") (Figs 1 and 2). There was no mucosal involvement nor hand and feet affection involvement. The itching had stopped, and there was no scratching

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.

Different neurological manifestations of COVID-19 in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicenter observational study using the International Severe Acute Respiratory and emerging Infection Consortium cohort across 1507 sites worldwide from January/30th/2020 to May/25th/2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161,239 patients (158,267 adults; 2,972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%), and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%), and central nervous system (CNS) infection (0.2%). Each occurred more frequently in ICU than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU vs. non-ICU (7.1% vs. 2.3%, P &lt; .001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease, and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure, and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

IntroductionInterstitial lung diseases (ILD) can be caused by mutations in the SFTPA1 and SFTPA2 genes, which encode the surfactant protein complex (SP)-A. Only 11 SFTPA1/2 mutations have so far been reported worldwide, of which 5 have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenic SFTPA1 or SFTPA2 mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives.MethodsThe consequences of the 11 SFTPA1/2 mutations were analysed both in vitro by studying the production and secretion of the corresponding mutated proteins and ex vivo by analysing SP-A expression on lung tissue samples. The associated disease phenotypes were documented.ResultsFor the 11 identified mutations, protein production was preserved, but secretion was abolished. The expression pattern of lung SP-A, available in 6 patients, was altered. The family history reported ILD and/or lung adenocarcinoma in 13/14 (93%) families. Among the 28 SFTPA1/2 mutation carriers, the mean age at ILD onset was 45 [0.6–65] years and 48% of them underwent lung transplantation (mean age 51); 7 carriers were asymptomatic.DiscussionThis study, which expands the molecular and clinical spectrum of SP-A disorders, shows that those pathogenic SFTPA1/A2 mutations share similar consequences on SP-A secretion in cell models and lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of the disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.

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.

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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.