Endogenous Antibody Responses to SARS-CoV-2 in Patients With Mild or Moderate COVID-19 Who Received Bamlanivimab Alone or Bamlanivimab and Etesevimab Together

BackgroundNeutralizing monoclonal antibodies (mAbs) to SARS-CoV-2 are clinically efficacious when administered early, decreasing hospitalization and mortality in patients with mild or moderate COVID-19. We investigated the effects of receiving mAbs (bamlanivimab alone and bamlanivimab and etesevimab together) after SARS-CoV-2 infection on the endogenous immune response.MethodsLongitudinal serum samples were collected from patients with mild or moderate COVID-19 in the BLAZE-1 trial who received placebo (n=153), bamlanivimab alone [700 mg (n=100), 2800 mg (n=106), or 7000 mg (n=98)], or bamlanivimab (2800 mg) and etesevimab (2800 mg) together (n=111). A multiplex Luminex serology assay measured antibody titers against SARS-CoV-2 antigens, including SARS-CoV-2 protein variants that evade bamlanivimab or etesevimab binding, and SARS-CoV-2 pseudovirus neutralization assays were performed.ResultsThe antibody response in patients who received placebo or mAbs had a broad specificity. Titer change from baseline against a receptor-binding domain mutant (Spike-RBD E484Q), as well as N-terminal domain (Spike-NTD) and nucleocapsid protein (NCP) epitopes were 1.4 to 4.1 fold lower at day 15-85 in mAb recipients compared with placebo. Neutralizing activity of day 29 sera from bamlanivimab monotherapy cohorts against both spike E484Q and beta variant (B.1.351) were slightly reduced compared with placebo (by a factor of 3.1, p=0.001, and 2.9, p=0.002, respectively). Early viral load correlated with the subsequent antibody titers of the native, unmodified humoral response (p<0.0001 at Day 15, 29, 60 and 85 for full-length spike).ConclusionsPatients with mild or moderate COVID-19 treated with mAbs develop a wide breadth of antigenic responses to SARS-CoV-2. Small reductions in titers and neutralizing activity, potentially due to a decrease in viral load following mAb treatment, suggest minimal impact of mAb treatment on the endogenous immune response.

A Market-Driven Management Model for Renewable-Powered Undergrid Mini-Grids

Renewable-powered “undergrid mini-grids” (UMGs) are instrumental for electrification in developing countries. An UMG can be installed under a—possibly unreliable— main grid to improve the local reliability or the main grid may “arrive” and connect to a previously isolated mini-grid. Minimising costs is key to reducing risks associated with UMG development. This article presents a novel market-logic strategy for the optimal operation of UMGs that can incorporate multiple types of controllable loads, customer smart curtailment based on reliability requirements, storage management, and exports to and imports from a main grid, which is subject to failure. The formulation results in a mixed-integer linear programming model (MILP) and assumes accurate predictions of the following uncertain parameters: grid spot prices, outages of the main grid, solar availability and demand profiles. An AC hybrid solar-battery-diesel UMG configuration from Nigeria is used as a case example, and numerical simulations are presented. The load-following (LF) and cycle-charging (CC) strategies are compared with our predictive strategy and HOMER Pro’s Predictive dispatch. Results prove the generality and adequacy of the market-logic dispatch model and help assess the relevance of outages of the main grid and of spot prices above the other uncertain input factors. Comparison results show that the proposed market-logic operation approach performs better in terms of cost minimisation, higher renewable fraction and lower diesel use with respect to the conventional LF and CC operating strategies.

Optimal Sizing and Assessment of a Renewable Rich Standalone Hybrid Microgrid Considering Conventional Dispatch Methodologies

This paper presents an evaluation of the optimized design of an off-grid hybrid microgrid for alternative load dispatch algorithms with the determination of the most optimal sizing of each equipment, analyzing the voltage and frequency outputs and various costs of the proposed microgrids. Kushighat and Rajendro Bazar, two geographical locations in Bangladesh have been taken as test sites. The proposed microgrids incorporating diesel generator, renewable resources, storage device, and 23.31 kW of demand have been optimized for five conventional load dispatch methodologies: HOMER predictive dispatch, Load Following, Generator Order, Cycle Charging, and Combined Dispatch to reduce the system’s net present cost, gas discharge and cost of energy. HOMER (Hybrid Optimization of Multiple Electric Renewables) software has been used for the analysis to determine the optimal sizes and costing and the voltage-frequency performances of the microgrids are analyzed using MATLAB/Simulink. From our analysis, load following is determined as the superior approach with a minimum operating cost of 3738 USD, net present cost of 152,023 USD, CO2 discharge of 3375 kg/year and cost of energy of 0.208 USD /kWh along with a steady voltage-frequency output. Combined dispatch is determined as the worst strategy for the proposed microgrids with the highest energy cost of 0.532 USD /kWh, the operational cost of 15,394 USD, net present cost of 415,030 USD, and high CO2 discharge. At the end of this work, a comparative analysis between the proposed design, another hybrid, and traditional generation plant is also presented. The findings of this work will be appropriate for any location with an identical demand profile and meteorological estate.

Selection of Appropriate Dispatch Strategies for Effective Planning and Operation of a Microgrid

The power system responsiveness may be improved by determining the ideal size of each component and performing a reliability analysis. This study evaluated the design and optimization of an islanded hybrid microgrid system with multiple dispatch algorithms. As the penetration of renewable power increases in microgrids, the importance and influence of efficient design and operation of islanded hybrid microgrids grow. The Kangaroo Island in South Australia served as the study’s test microgrid. The sizing of the Kangaroo Island hybrid microgrid system, which includes solar PV, wind, a diesel engine, and battery storage, was adjusted for four dispatch schemes. In this study, the following dispatch strategies were used: (i) load following, (ii) cycle charging, (iii) generator order, and (iv) combination dispatch. The CO2 emissions, net present cost (NPC), and energy cost of the islanded microgrid were all optimized (COE). The HOMER microgrid software platform was used to build all four dispatch algorithms, and DIgSILENT PowerFactory was used to analyze the power system’s responsiveness and dependability. The findings give a framework for estimating the generation mix and required resources for an islanded microgrid’s optimal functioning under various dispatch scenarios. According to the simulation results, load following is the optimum dispatch technique for an islanded hybrid microgrid that achieves the lowest cost of energy (COE) and net present cost (NPC).

Cetylpyridinium chloride (CPC) reduces zebrafish mortality from influenza infection: Super-resolution microscopy reveals CPC interference with multiple protein interactions with phosphatidylinositol 4,5-bisphosphate in immune function

The COVID-19 pandemic raises significance for a potential influenza therapeutic compound, cetylpyridinium chloride (CPC), which has been extensively used in personal care products as a positively-charged quaternary ammonium antibacterial agent. CPC is currently in clinical trials to assess its effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) morbidity. Two published studies have provided mouse and human data indicating that CPC may alleviate influenza infection, and here we show that CPC (0.1 uM, 1 hour) reduces zebrafish mortality and viral load following influenza infection. However, CPC mechanisms of action upon viral-host cell interaction are currently unknown. We have utilized super-resolution fluorescence photoactivation localization microscopy to probe the mode of CPC action. Reduction in density of influenza viral protein hemagglutinin (HA) clusters is known to reduce influenza infectivity: here, we show that CPC (at non-cytotoxic doses, 5-10 uM) reduces HA density and number of HA molecules per cluster within the plasma membrane of NIH-3T3 mouse fibroblasts. HA is known to colocalize with the negatively-charged mammalian lipid phosphatidylinositol 4,5-bisphosphate (PIP2); here, we show that nanoscale co-localization of HA with the PIP2-binding Pleckstrin homology (PH) reporter in the plasma membrane is diminished by CPC. CPC also dramatically displaces the PIP2-binding protein myristoylated alanine-rich C-kinase substrate (MARCKS) from the plasma membrane of rat RBL-2H3 mast cells; this disruption of PIP2 is correlated with inhibition of mast cell degranulation. Together, these findings offer a PIP2-focused mechanism underlying CPC disruption of influenza and suggest potential pharmacological use of this drug as an influenza therapeutic to reduce global deaths from viral disease.