Background: There is currently no treatment known to alter the course of coronavirus disease 2019 (COVID-19). Convalescent plasma has been used to treat a number of infections during pandemics, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and now severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Objectives: To summarize the existing literature and registered clinical trials on the efficacy and safety of convalescent plasma for treating coronaviruses, and discuss issues of feasibility, and donor and patient selection. Sources: A review of articles published in PubMed was performed on 13 July 2020 to summarize the currently available evidence in human studies for convalescent plasma as a treatment for coronaviruses. The World Health Organization International Clinical Trials Registry and clinicaltrials.gov were searched to summarize the currently registered randomized clinical trials for convalescent plasma in COVID-19. Content: There were sixteen COVID-19, four MERS and five SARS reports describing convalescent plasma use in humans. There were two randomized control trials, both of which were for COVID-19 and were terminated early. Most COVID-19 reports described a potential benefit of convalescent plasma on clinical outcomes in severe or critically ill patients with few immediate adverse events. However, there were a number of limitations, including the concurrent use of antivirals, steroids and other treatments, small sample sizes, lack of randomization or control groups, and short follow-up time. Data from SARS and COVID-19 suggest that earlier administration probably yields better outcomes. The ideal candidates for recipients and donors are not known. Still, experience with previous coronaviruses tells us that antibodies in convalescent patients are probably short-lived. Patients who had more severe disease and who are earlier in their course of recovery may be more likely to have adequate titres. Finally, a number of practical challenges were identified. Implications: There is currently no effective treatment for COVID-19, and preliminary trials for convalescent plasma suggest that there may be some benefits. However, research to date is at high risk of bias, and randomized control trials are desperately needed to determine the efficacy and safety of this therapeutic option.
The protein requirement estimate of 1.41 and 1.71 g·kg·d for females performing variable-intensity intermittent exercise is greater than the IAAO-derived estimates of adult males (0.93 and 1.2 g·kg·d) and at the upper range of the American College of Sports Medicine athlete recommendations (1.2-2.0 g·kg·d).
BackgroundMuscle protein synthesis and muscle net balance plateau after moderate protein ingestion in adults. However, it has been suggested that there is no practical limit to the anabolic response of whole-body net balance to dietary protein. Moreover, limited research has addressed the anabolic response to dietary protein in adolescents. The present study determined whether whole-body net balance plateaued in response to increasing protein intakes during post-exercise recovery and whether there were age- and/or sex-related dimorphisms in the anabolic response.MethodsThirteen adults [7 males (M), 6 females (F)] and 14 adolescents [7 males (AM), 7 females (AF) within ~ 0.4 y from peak height velocity] performed ~ 1 h variable intensity exercise (i.e., Loughborough Intermittent Shuttle Test) prior to ingesting hourly mixed meals that provided a variable amount of protein (0.02–0.25 g·kg− 1·h− 1) as crystalline amino acids modeled after egg protein. Steady-state protein kinetics were modeled noninvasively with oral L-[1-13C]phenylalanine. Breath and urine samples were taken at plateau to determine phenylalanine oxidation and flux (estimate of protein breakdown), respectively. Whole-body net balance was determined by the difference between protein synthesis (flux – oxidation) and protein breakdown. Total amino acid oxidation was estimated from the ratio of urinary urea/creatinine.ResultsMixed model biphasic linear regression explained a greater proportion of net balance variance than linear regression (all, r2 ≥ 0.56; P < 0.01), indicating an anabolic plateau. Net balance was maximized at ~ 0.15, 0.12, 0.12, and 0.11 g protein·kg− 1·h− 1 in M, F, AM, and AF, respectively. When collapsed across age, the y-intercept (net balance at very low protein intake) was greater (overlapping CI did not contain zero) in adolescents vs. adults. Urea/creatinine excretion increased linearly (all, r ≥ 0.76; P < 0.01) across the range of protein intakes. At plateau, net balance was greater (P < 0.05) in AM vs. M.ConclusionsOur data suggest there is a practical limit to the anabolic response to protein ingestion within a mixed meal and that higher intakes lead to deamination and oxidation of excess amino acids. Consistent with a need to support lean mass growth, adolescents appear to have greater anabolic sensitivity and a greater capacity to assimilate dietary amino acids than adults.
RationaleExposure to air pollution is linked with increased asthma morbidity and mortality. To understand pathological processes linking air pollution and allergen exposures to asthma pathophysiology, we investigated the effect of coexposure to diesel exhaust (DE) and aeroallergen on immune regulatory proteins in human airways.MethodsFourteen allergen-sensitised participants completed this randomised, double-blinded, cross-over, controlled exposure study. Each participant underwent four exposures (allergen-alone exposure, DE and allergen coexposure, particle-depleted DE (PDDE) and allergen coexposure, and sham exposure) on different order-randomised dates, each separated by a 4-week washout. Serum and bronchoalveolar lavage (BAL) were assayed for pattern recognition molecules, cytokines, chemokines and inflammatory mediators.ResultsIn human airways, allergen-alone exposure led to accumulation of surfactant protein D (SPD; p=0.02). Coexposure to allergen and DE did not elicit the same increase of SPD as did allergen alone; diesel particulate reduction restored allergen-induced SPD accumulation. Soluble receptor for advanced glycation end products was higher with particle reduction than without it. In the systemic circulation, there was a transient increase in SPD and club cell protein 16 (CC16) 4 hours after allergen alone. CC16 was augmented by PDDE, but not DE. % eosinophils in BAL (p<0.005), eotaxin-3 (p<0.0001), interleukin 5 (IL-5; p<0.0001) and thymus and activation regulated chemokine (p=0.0001) were each increased in BAL by allergen. IL-5, SPD and % eosinophils in BAL were correlated with decreased FEV1.ConclusionShort-term coexposure to aeroallergen and DE alters immune regulatory proteins in lungs; surfactant levels are dependent on particle depletion.Trial registration numberNCT02017431.
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