BACKGROUNDPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive.METHODSWe conducted a randomized, ...open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation ECMO), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population.RESULTSBetween April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19-1.14, log-rank P = 0.087).CONCLUSIONCP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant.TRIAL REGISTRATIONClinicaltrials.gov, NCT04345523.FUNDINGGovernment of Spain, Instituto de Salud Carlos III.
Bacillus thuringiensis Berliner 1915 (Bt) is an entomopathogenic bacterium used to control insect pest worldwide. During its life cycle, Bt produces different insecticidal proteins, among which ...Vegetative Insecticidal Proteins (Vip) and Crystal proteins (Cry) are the most commercially used. Although large number of Bt toxins have been reported, only few of them (such as Cry1Ca and Vip3Aa) showed toxicity to the cosmopolitan pest Spodoptera exigua (Hübner) (Lepidoptera:Noctuidae). Diverse strategies have been developed to enhance the toxicity of Bt toxins and to delay the onset of resistance, including the addition of synergistic agents. Several synergistic compounds are based on Cry receptors. Especially cadherin receptor is one of the most widely studied and characterised across-taxa. In this regard, the insect cadherin fragments can enhance the toxicity of Cry insecticidal toxins, although less is known about the interaction between cadherin fragments and Vip toxins. The purpose of this work is to study the synergistic effect on toxicity of two different cadherin fragments (from Tenebrio molitor (Linnaeus) (Coleoptera: Tenebrionidae) and S. exigua) with two Bt toxins (Cry1Ca and Vip3Aa) on the lepidopteran pests S. exigua and Grapholita molesta (Busck) (Lepidoptera:Tortricidae). In our methodology, single dose response assays at different Bt protein:cadherin fragment ratios were performed. Upon potential synergistic results, the selected mixture was accurately analysed by dose-response bioassays to verify toxicity enhancement. However, no robust synergistic effect was observed after testing all the combinations of insect species-toxin-cadherin fragment, confirming that synergistic effects of cadherin fragments may not be generalised for all combinations.
PDF
