Background We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. Methods In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov , NCT04501978 . Findings Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–...

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Objective Surgical management of aortic valve infective endocarditis (IE) with cryopreserved homograft has been associated with lower risk of recurrent IE, but there is equipoise with regard to the optimal prosthesis. This systematic review and meta-analysis were performed to compare outcomes between homograft and conventional prosthesis for aortic valve IE. Methods We searched MEDLINE database to September 2017 for studies comparing homograft versus conventional prosthesis. The main outcomes were all-cause mortality, recurrent IE, and reoperation. Results There were 18 included comparative observational studies with 2232 patients (median follow up = 5 [interquartile range: 2–7] years, 30% prosthetic valve endocarditis); four studies were adjusted for baseline differences. There were no differences in perioperative mortality or stroke despite a greater proportion of staphylococcal endocarditis, abscess, and root replacements but less multivalve involvement in the homograft group. Long-term outcomes of all-cause mortality [incidence rate ratio (IRR) = 1.03, 95% confidence interval (CI) = 0.81–1.31, P = 0.83, for unmatched, and IRR = 0.82, 95% CI = 0.36–1.84, P = 0.63, for matched studies], recurrent endocarditis (IRR = 1.01, 95% CI = 0.53–1.93, P = 0.96, for unmatched, and IRR = 1.04, 95% CI = 0.49–2.19, P = 0.92, for matched studies), and reoperation (IRR = 1.60, 95% CI = 0.80–3.21, P = 0.18, for unmatched, and IRR = 3.17, 95% CI = 0.52–19.44, P = 0.21, for matched studies) were not different comparing homograft versus conventional prosthesis. There was a significantly increased need for reoperation with homograft versus mechanical prosthetic valves, but this comparison was based on limited data. Conclusions Homografts and conventional prostheses offer similar survival and freedom from recurrent endocarditis and reoperation for aortic valve IE. Homografts may be associated with greater risk of reoperation compared with mechanical valves.

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ACTIV-3/TICO Study Group* Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.