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.

Aims Advances have been made over the last decade in the management of cardiac amyloidosis (CA), but a delayed diagnosis is still common. The aim of this study was to describe the journey to CA diagnosis from initial clinical and to analyse time to diagnosis. Methods and results Between January 2001 and May 2019, 270 consecutive patients with CA diagnosed at Toulouse University Hospital were retrospectively included in this cross-sectional study: 111 (41%) light chain amyloidosis, 122 (45%) wild-type transthyretin amyloidosis, and 37 (14%) hereditary transthyretin amyloidosis. CA onset occurred mostly with dyspnoea (50%) or systematic follow-up (10%). The cardiologist was the first line specialist in 68% of patients, followed by the nephrologist (9%) and neurologist (8%). Patients encountered a median (minimum-maximum) number of two (1-7) physician specialists and performed a median (minimum-maximum) number of three (1-8) tests before diagnosis. Median delay between symptom onset and CA diagnosis was 8 [IQR 5-14], 10 [IQR 3-34], and 18 [IQR 4-49] months, respectively, in light chain amyloidosis, wild-type transthyretin amyloidosis, and hereditary transthyretin amyloidosis subgroups (P = .060). Having performed electromyography or spirometry was associated with a longer delay in diagnosis in the overall population: odds ratio = 1.13; 95% confidence interval 1.02 to 1.24; and odds ratio = 1.13; 1.03 to 1.24, respectively, probably due to non-specific initial symptoms. Conclusions CA is a protean disease with various first line specialists causing a diagnostic wandering despite increasing medical community awareness. It requires a multidisciplinary specialist care networks to educate and manage symptoms and therapies.

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.