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 ...

Université Pierre et Marie Curie, Paris, France.

We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.

We described the largest cohort of severe systemic capillary-leak syndrome flares requiring ICU admission. High-volume fluid therapy was independently associated with poorer outcomes. IV immunoglobulin use was not associated with improved survival; hence, their use should be considered prudently and needs further evaluation in future studies.