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.

Data on the novel coronavirus disease 2019 (COVID-19) in children are limited, and studies from Europe are scarce. We analyzed the clinical severity and epidemiologic aspects of COVID-19 in consecutive children aged 0–18 years, referred with a suspicion of COVID-19 between February 1, and April 15, 2020. RT-PCR on a nasopharyngeal swab was used to confirm COVID-19. 319 children met the criteria of a suspected case. COVID-19 was diagnosed in 15/319 (4.7%) patients (8 male; mean age 10.5 years). All of them had household contact with an infected relative. Five (33.3%) patients were asymptomatic. In 9/15 (60.0%) children, the course of the disease was mild, and in 1/15 (6.7%), it was moderate, with the following symptoms: fever (46.7%), cough (40%), diarrhea (20%), vomiting (13.3%), rhinitis (6.7%), and shortness of breath (6.7%). In the COVID-19-negative patients, other infections were confirmed, including influenza in 32/319 (10%). The clinical course of COVID-19 and influenza differed significantly based on the clinical presentation. In conclusion, the clinical course of COVID-19 in children is usually mild or asymptomatic. In children suspected of having COVID-19, other infections should not be overlooked. The main risk factor for COVID-19 in children is household contact with an infected relative.

Liver disease in HIV-infected patients may result from the infection itself, antiretroviral treatment or comorbidities. In this study, we analysed liver disease in 79 HIV-infected children and adolescents aged 14.0 ± 5.1 years. All the patients were receiving combination antiretroviral therapy (cART), with a mean duration of 11.5 ± 4.7 years. Six patients (8%) had detectable HIV viral load, and 8/79 (10%) of the participants were coinfected with hepatitis B or C virus (HCV, 6/8 or HBV, 2/8). Liver disease was defined as an elevation of any of the following parameters: alanine or aspartate aminotransferase (ALT and AST), total bilirubin, and gamma glutamyl transferase (GGTP). For the noninvasive evaluation of liver fibrosis, the AST-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) were calculated. Liver disease was diagnosed in 20/79 (25%) of the patients, including 13/71 (18%) of participants without coinfection and 7/8 (88%) with coinfection (p < 0.0001). All of the liver markers except bilirubin were significantly higher in the coinfected group. APRI scores indicated significant fibrosis in 5/8 (63%) of patients with coinfection. HBV or HCV coinfection and detectable HIV viral load were independently positively associated with APRI (p = 0.0001, and p = 0.0001) and FIB-4 (p = 0.001, and p = 0.002, respectively). In conclusion, liver disease in HIV-infected children and adolescents results mainly from HBV or HCV coinfection. Effective antiretroviral treatment is protective against hepatic abnormalities.

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.