Aims The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.

Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

Background The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov , NCT04315948 . Findings Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporea...

Asymptomatic infection and atypical manifestations of COVID-19: Comparison of viral shedding duration Dear Editor,Coronavirus disease 2019 (COVID-19) bears several challenging problems, including insidious symptom onset, subclinical manifestations and highly transmissible property during early stage of infection. 1 In the recent study by Huang et al., SARS-CoV-2infection presented strong infectivity during the incubation period with rapid transmission. 2 Some patients with COVID-19 are asymptomatic, while others complain of atypical symptoms including loss of smell and taste sense. 3 However, there is insufficient data on the prevalence of asymptomatic infection and atypical manifestations of COVID-19. In this study, we aimed to evaluate the prevalence of asymptomatic infection, anosmia (smell loss) and ageusia (taste loss) among patients with mild COVID-19 in a residential treatment center (RTC). We also compared the duration of SARS-CoV-2 viral shedding between groups with different clinical manifestations.An observational cohort study was conducted for 199 patients with COVID-19 in a RTC at Gyeongju, Gyeongsangbuk province, Republic of Korea (ROK). The RTC was introduced to care patients with mild COVID-19 for the efficient distribution of limited medical resources during large epidemic in early March 2020. Data on demographic findings, symptoms, and duration of viral shedding were collected. The patients were interviewed about initial symptoms and their duration in detail. Real-time PCR (RT-PCR) to detect SARS-CoV-2 was performed every 2-7 days. Duration of viral shedding was considered as time from diagnosis date to the day before first negative conversion of two consecutive negative results of RT-PCR. RT-PCR was conducted using Allplex 2019-nCoV assay (Seegene, Seoul, South Korea). Statistical analyses were performed using SPSS 20.0 program. Mann-Whitney U test was performed to compare the duration of viral shedding between groups with different clinical manifestations. P -value < 0.05 was considered statistically significant. This study was approved by the Institutional Review Board of Korea University Guro Hospital (approval number: 2020GR0135).Among 199 patients with COVID-19, male was 34.7% and mean age of the patients was 38.0 years ( Table 1 ). Most patients (187, 94.0%) were healthy without chronic medical conditions. Among 199 patients, 26.6% were asymptomatic. In the early study, asymptomatic cases accounted for 10.7% (3/28) of COVID-19 cases in the ROK. 1 Asymptomatic proportion of COVID-19 was estimated as 17.9% (95% credible interval, 15.5-20.2%) on the Diamond Princess cruise ship, Japan. 4 Among clinical manifestations, cough (41.2%) was most common, followed by rhinorrhea and nasal stuffiness (30.2%). Of note, 26.1% (52/199) of patients presented anosmia, and 22.6% (45/199) complained of ageusia. Thirty-eight (19.1%) patients complained of both anosmia and ageusia. Duration of anosmia and Duration of viral shedding (days, mean ± SD) p value Asymptomatic 22.6 ± 4.0 < 0.01 * Symptomatic 25.2 ...

Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.

C, Mentre F, on behalf of the DisCoVeRy study group, An open-label randomized, controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with Clinical Microbiology and Infection,

Objectives To assess changes in characteristics and management among ST‐elevation myocardial infarction (STEMI) patients with coronavirus disease (COVID‐19) who underwent primary percutaneous coronary intervention. Methods Our prospective, monocentric study enrolled all STEMI patients who underwent PPCI during the COVID‐19 outbreak ( n = 83). This cohort was first compared with a previous cohort of STEMI patients (2008–2017, n = 1,552 patients) and was then dichotomized into a non‐COVID‐19 group ( n = 72) and COVID‐19 group ( n = 11). Results In comparison with the pre‐outbreak period, patients during the outbreak period were older (59.6 ± 12.9 vs. 62.6 ± 12.2, p = .03) with a delayed seek to care (mean delay first symptoms‐balloon 3.8 ± 3 vs. .7.4 ± 7.7, p < .001) resulting in a two‐fold higher in‐hospital mortality (non COVID‐19 4.3% vs. COVID‐19 8.4%, p = .07). Among the 83 STEMI patients admitted during the outbreak period, 11 patients were infected by COVID‐19. Higher biological markers of inflammation (C‐reactive protein: 28 ± 39 vs. 98 ± 97 mg/L, p = .04), of fibrinolysis (D‐dimer: 804 ± 1,500 vs. 3,128 ± 2,458 μg/L, p = .02), and antiphospholipid antibodies in four cases were observed in the COVID‐19 group. In this group, angiographic data also differed: a thrombotic myocardial infarction nonatherosclerotic coronary occlusion (MINOCA) was observed in 11 cases (1.4% vs. 54.5%, p < .001) and associated with higher post‐procedure distal embolization (30.6% vs. 72.7%, p = .007). The in hospital mortality was significantly higher in the COVID‐19 group (5.6% vs. 27.3%, p = .016). Conclusion The COVID‐19 outbreak implies deep changes in the etiopathogenesis and therapeutic management of STEMI patients with COVID‐19. The impact on early and long‐term outcomes of systemic inflammation and hypercoagulability in this specific population is warranted.

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.