Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

How we secured a COVID-19 convalescent plasma procurement scheme in Japan.

BACKGROUND: In order to tackle the COVID-19 pandemic, a COVID-19 convalescent plasma (CCP) procurement program was initiated in Japan in April 2020. The program was a collaboration between a government-managed national hospital, an infectious disease research institute, and a blood banking organization. Each party assumed different responsibilities: recruitment, SARS-CoV-2 antibody profiling, and plasmapheresis; conduction of screening tests; and SARS-CoV-2 blood testing, respectively. METHODS: We adopted a two-point screening approach before the collected CCP was labeled as a CCP product for investigational use, for which we mainly tested anti-SARS-CoV-2 antibody eligibility and blood product eligibility. Anti-SARS-CoV-2 spike protein titer was measured using enzyme-linked immunosorbent assay, and the IC50 value was denoted as the neutralizing activity. Blood donor eligibility was extended beyond the normal blood donation guidelines to include a broader range of participants. After both eligibility criteria were confirmed, participants were asked to revisit the hospital for blood donation, which is a unique aspect of the Japanese CCP program, as most donations are taking place in normal blood donation venues in other countries. Some donors were re-scheduled for repeat plasma donations. As public interest in anti-SARS-CoV-2 antibodies increased, test results were given to the participants. RESULTS: As of September 17, 2020, our collection of CCP products was sufficient to treat more than 100 patients. As a result, projects for administration and distribution are also being conducted. CONCLUSIONS: We successfully implemented a CCP procurement scheme with the goal to expand to other parts of the country to improve treatment options for COVID-19.

Consumption of a structured triacylglycerol containing behenic and oleic acids increases fecal fat excretion in humans.

We examined the fecal fat excretion of mildly hypertriacylglycerolemic subjects who ingested soft cookies containing 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) for 7 days. The subjects included 14 healthy men (average age; 44.9 ± 1.7) whose fasting plasma triacylglycerol level ranged from 150 to 250 mg/dL. Every day for 7 days, the subjects ate 5 soft cookies containing margarine with the BOO-rich experimental oil (BOO intake, 2.46 g/day). The placebo group ate soft cookies containing margarine without BOO. This study was a randomized double-blind, placebo-controlled, crossover study. Feces were collected for 3 days prior to the end of the treatment period, and fecal fat and fatty acid composition were determined. The fecal wet weight was significantly increased in BOO group compared with that in the placebo group. Moreover, fecal fat and fatty acid level were significantly higher in the BOO group than in the placebo group. There were no significant differences in the fecal fatty acid composition of the BOO and placebo groups. These results suggest that dietary BOO increases fecal excretion of dietary fat in humans. However, BOO does not increase the excretion of specific fatty acids; it increases the excretion of all fatty acids of dietary origin, which may lead to lower and delay intestinal absorption of dietary fat.

Structured triacylglycerol containing behenic and oleic acids suppresses triacylglycerol absorption and prevents obesity in rats.

BACKGROUND: Dietary 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG) absorption were investigated in rats. METHODS: In Experiment 1, rats were fed either BOO or soybean oil (SO) diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO) or an oil mixture (OOO:BOO, 9:1). Tri[1-14C]oleoylglycerol (14C-OOO) was added to the emulsions administered in Experiment 3. RESULTS: No observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration. CONCLUSIONS: These results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG.

[Clinical pathway for management of patients with acute asthma attack].

BACKGROUND: There have been few reports of clinical pathway (CP) for treatment of asthma attack, because patients with asthma always admit emergently and the severity varies. We introduced CP so that standard asthma treatment can be widely used, and investigated its clinical usefulness. METHODS: We designed a new CP for treating asthma attack according to the guideline (Japanese guideline (JGL) and Global Initiative for Asthma (GINA)). 136 patients who admitted to our hospital due to asthma attack from January 1999 to November 2006, were enrolled our study. Excluding cases complicated with pneumonia, COPD or cardiac failure, we evaluated 46 cases treated with the CP comparing with 19 cases treated without the CP. The clinical evaluations include systemic and inhaled steroid use, FEV1.0%, history of asthma, and the duration of asthma attack. Furthermore, we investigated difference between cases with and without prolonged admission. RESULTS: While the rates of systemic and inhaled steroid use in cases without the CP were 57.9% and 52.6% respectively, those in cases with the CP were approximately 100%. Employing the CP, FEV 1.0% at discharge time was elevated from 71.7% to 76.3% and the duration of hospitalization was shortened from 14.2 days to 11.5 days. Mean age of the cases with prolonged admission was higher than the rest. CONCLUSION: The asthma CP is an effective way for the standard treatment according to the guideline to be used widely even by doctors who are not familiar with asthma treatment. It improves the efficacy of in-hospital treatment.

Effects of soybean beta-conglycinin on hepatic lipid metabolism and fecal lipid excretion in normal adult rats.

beta-Conglycinin decreased blood triacylglycerol (TAG) levels in male Wistar adult rats. Liver mitochondrial carnitine palmitoyltransferase activity in the beta-conglycinin-fed group significantly increased as against the casein-fed group. Hepatic fatty acid synthase activity in the beta-conglycinin group significantly decreased as against that of the casein-fed group. Fecal fatty acid excretion in the beta-conglycinin group was significantly higher than in the casein group.

Divergent effects of soy protein diet on the expression of adipocytokines.

Adipose tissue secretes various bioactive molecules called adipocytokines. Dysregulation of adipocytokines plays an important role in the development of atherosclerotic vascular diseases. Consumption of vegetable protein reduces the risks of atherosclerotic vascular diseases. Here, we investigated the effects of 10-day dietary soy protein isolate (SPI) on the regulation of adipocytokines in Wistar rats. No significant difference in body weight was observed between SPI and Casein (animal protein) group. Expression of adipose PAI-1 was lower and expression and plasma concentration of adiponectin were higher in SPI than Casein group. Triglyceride content was lower and fatty acid synthase mRNA level in adipose tissue was lower in SPI than Casein group. Although SREBP-1 mRNA expression was decreased in the liver of SPI group, adipose SREBP and PPARgamma mRNA levels remained unchanged. Our data suggest that dietary SPI alters the gene expressions in adipose tissue and has beneficial effects on the expression of adipocytokines.