THE EFFECT OF BROMELAIN MICROCAPSUL FORMULATION ON LEUKOCYTE AND TNF-α LEVEL IN MALE WHITE MICE INDUCED BY H5N1 VACCINE

Objective: Bromelain is a sulfhydryl proteolytic enzyme extracted from the pineapple plant (Ananas comosus. L), which has various activities, including as an immunomodulator. Microencapsulation of bromelain is a process by which a layer surrounds bromelain to produce microcapsules to increase its activity. This research intends to see the effect of bromelain microcapsule formulation on total leukocytes count, leukocyte percentage, and the levels of TNF-α in male white mice exposed to the H5N1 Vaccine. Methods: Experimental animals were divided into three groups, specifically a negative control group given Na CMC 0.5%, the comparison group given 200 mg/kgBW bromelain enzyme, and the test group given 200 mg/kgBW bromelain microcapsules for seven days orally. On the eighth day, the total amount and the percentage of leukocytes and the levels of TNF-α were counted. The data were analyzed by two-way ANOVA and Duncan’s multiple range test (p<0.05). Results: The study showed that the administration of 200 mg/kgBW bromelain microcapsule group significantly reduced total leukocyte count and increased the segmented neutrophil compared to the bromelain group (p<0.05). However, there was no significant correlation between the two groups in reducing monocyte, lymphocyte, eosinophil, and TNF-α levels (p>0.05). Conclusion: It can be concluded that providing bromelain microcapsules can reduce the total amount of leukocytes and increase the segmented neutrophil in male white mice exposed to the H5N1 Vaccine

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed