The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.
The purpose was to investigate the effects of high-velocity resistance training (HVRT) and creatine supplementation in untrained healthy aging males. Participants were randomized to supplement with creatine (0.1 g·kg−1·day−1 of creatine + 0.1 g·kg−1·day−1 of maltodextrin) or placebo (0.2 g·kg−1·day−1 of maltodextrin) during 8 weeks of HVRT. Prior to and following HVRT and supplementation, assessments were made for muscle strength, muscle thickness, peak torque, and physical performance. There was a significant increase over time for all measures of muscle strength (p < 0.001), muscle thickness (p < 0.001), and some measures of peak torque (knee flexion; 1.05 and 3.14 rad/s; p < 0.001) and physical performance (balance board time-to-completion; p = 0.017). There was a group × time interaction for leg press strength (p = 0.044) and total lower-body strength (leg press, knee flexion, knee extension combined; p = 0.039). The creatine group experienced greater gains in leg press and total lower-body strength compared with the placebo group, with no other differences. HVRT increases muscle strength, muscle thickness, and some measures of peak torque and physical performance in untrained healthy aging males. The addition of creatine supplementation to HVRT further augments the gains in leg press and total lower-body strength. Novelty High-velocity resistance training increases muscle mass and performance. Creatine supplementation increases lower-body muscle strength. High-velocity resistance training and creatine supplementation are safe interventions for aging adults.
Brad Schoenfeld declares that he serves on the advisory board for Dymatize Nutrition, a manufacturer of sports supplements. He was not involved in the data collection process for the study; his contribution was to assist in the interpretation of findings and write-up of the manuscript.
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