Vaccination coverage and breakthrough infections of COVID-19 during the second wave among staff of selected medical institutions in India.

India experienced the second wave of SARS-CoV-2 infection from April 3 to June 10, 2021. During the second wave, Delta variant B.1617.2 emerged as the predominant strain, spiking cases from 12.5 million to 29.3 million (cumulative) by the end of the surge in India. Vaccines against COVID-19 are a potent tool to control and end the pandemic in addition to other control measures. India rolled out its vaccination programme on January 16, 2021, initially with two vaccines that were given emergency authorization-Covaxin (BBV152) and Covishield (ChAdOx1 nCoV- 19). Vaccination was initially started for the elderly (60+) and front-line workers and then gradually opened to different age groups. The second wave hit when vaccination was picking up pace in India. There were instances of vaccinated people (fully and partially) getting infected, and reinfections were also reported. We undertook a survey of staff (front line health care workers and supporting) of 15 medical colleges and research institutes across India to assess the vaccination coverage, incidence of breakthrough infections, and reinfections among them from June 2 to July 10, 2021. A total of 1876 staff participated, and 1484 forms were selected for analysis after removing duplicates and erroneous entries (n = 392). We found that among the respondents at the time of response, 17.6% were unvaccinated, 19.8% were partially vaccinated (received the first dose), and 62.5% were fully vaccinated (received both doses). Incidence of breakthrough infections was 8.7% among the 801 individuals (70/801) tested at least 14 days after the 2nd dose of vaccine. Eight participants reported reinfection in the overall infected group and reinfection incidence rate was 5.1%. Out of (N = 349) infected individuals 243 (69.6%) were unvaccinated and 106 (30.3%) were vaccinated. Our findings reveal the protective effect of vaccination and its role as an essential tool in the struggle against this pandemic.

Fabric phase sorptive extraction-gas chromatography-mass spectrometry for the determination of favipiravir in biological and forensic samples

Favipiravir, a pyrazine analog, is proposed as providential antiviral agent against the COVID-19 infection during 2020 pandemic emergency. For the first time, a fabric phase sorptive extraction (FPSE) combined with gas chromatography-mass spectrometry (GC-MS) has been developed and applied for the determination of favipiravir (FAV) in biological samples (human plasma, blood and urine), pharmaceutical and forensic samples. The method comprises of extraction of FAV by FPSE followed by its derivatization with N, O-bis (trimethylsilyl) trifluoroacetamide (BSTFA) and GC-MS analysis. Design of experiment-based optimization was performed using Placket-Burman Design (PBD) and Central Composite Design (CCD) for the screening of significant factors of FPSE and their optimization, respectively. Among all tested membranes, sol-gel polyethylene glycol (PEG) has offered the best extraction efficiency for FAV. Under optimum conditions, the proposed method was found to be linear in the range of 0.01–10 µg mL−1 by GC-MS. The LODs and LOQs were as low as 0.001-0.0026 μg mL−1 and 0.003-0.0086 μg mL−1, respectively by GC-MS. Intra-day and inter-day precisions were less than 5 and 10 %, respectively, showing good method precision. The proposed method has been successfully applied to detect and quantify FAV in human urine, whole blood and plasma samples along with seized forensic samples. In addition, the proposed method has been evaluated for its green character by ComplexGAPI index. Graphical Image, graphical

A Non-Instrumental Green Analytical Method Based on Surfactant-Assisted Dispersive Liquid-Liquid Microextraction-Thin-Layer Chromatography-Smartphone-Based Digital Image Colorimetry(SA-DLLME-TLC-SDIC) for Determining Favipiravir in Biological Samples.

Favipiravir (FAV) has become a promising antiviral agent for the treatment of COVID-19. Herein, a green, fast, high-sample-throughput, non-instrumental, and affordable analytical method is proposed based on surfactant-assisted dispersive liquid-liquid microextraction (SA-DLLME) combined with thin-layer chromatography-digital image colourimetry (TLC-DIC) for determining favipiravir in biological and pharmaceutical samples. Triton X-100 and dichloromethane (DCM) were used as the disperser and extraction solvents, respectively. The extract obtained after DLLME procedure was spotted on a TLC plate and allowed to develop with a mobile phase of chloroform:methanol (8:2, v/v). The developed plate was photographed using a smartphone under UV irradiation at 254 nm. The quantification of FAV was performed by analysing the digital images' spots with open-source ImageJ software. Multivariate optimisation using Plackett-Burman design (PBD) and central composite design (CCD) was performed for the screening and optimisation of significant factors. Under the optimised conditions, the method was found to be linear, ranging from 5 to 100 µg/spot, with a correlation coefficient (R2) ranging from 0.991 to 0.994. The limit of detection (LOD) and limit of quantification (LOQ) were in the ranges of 1.2-1.5 µg/spot and 3.96-4.29 µg/spot, respectively. The developed approach was successfully applied for the determination of FAV in biological (i.e., human urine and plasma) and pharmaceutical samples. The results obtained using the proposed methodology were compared to those obtained using HPLC-UV analysis and found to be in close agreement with one another. Additionally, the green character of the developed method with previously reported protocols was evaluated using the ComplexGAPI, AGREE, and Eco-Scale greenness assessment tools. The proposed method is green in nature and does not require any sophisticated high-end analytical instruments, and it can therefore be routinely applied for the analysis of FAV in various resource-limited laboratories during the COVID-19 pandemic.

Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.

BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment. OBJECTIVE: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high. DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multicenter trial. PATIENTS: Hospitalized patients with COVID-19 without end-organ failure. INTERVENTION: Bamlanivimab (7000 mg) or placebo. MEASUREMENTS: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections). RESULTS: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs. LIMITATION: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed. CONCLUSION: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Seroprevalence of SARS-CoV-2 IgG antibody among healthy blood donors: a single centre study.

BACKGROUND: Severe acute respiratory syndrome corona virus 2(SARS-CoV-2), the causative agent of corona virus disease-2019(COVID- 19) which has led to a global pandemic. The true extent of the burden of COVID-19 may be underestimated, and there is need to know the current prevalence of SARS-CoV-2 antibody in population. METHODS: The present study was a cross-sectional study to assess prevalence of SARS-CoV- 2 IgG antibody among 586 healthy voluntary blood donors who donated whole blood between mid-December 2020 to January 2021. A chemiluminescence assay was used to detect the presence of SARS-CoV-2 IgG antibody in serum samples in addition to recommended transfusion transmitted infections tests and Signal to Cut Off (S/C) > 1 was considered as reactive for antibody as per manufacturer's instructions. RESULTS: In the present study, 586 healthy voluntary blood donors were enrolled and were screened for SARS- CoV-2 IgG antibody. Out of 586 donors, 52 donors had indeterminate values of SARS-CoV-2 IgG antibody. A total of 534 healthy voluntary blood donors' samples were included in the present study for analysis. Out of total 534 healthy blood donors, 42.88% (229) were found to be seropositive while 57.11% (305) were found to be seronegative. CONCLUSION: A 43% positivity of SARS-CoV-2 IgG antibody among healthy blood donors was detected which is an indication of presence of infection at community level and majority of the population already has been exposed to SARS-CoV-2 infection. However, there was no statistically significant association of type of blood group and age with seropositivity.

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

BACKGROUND/AIMS: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public-private partnership initiated the Therapeutics for Inpatients with COVID-19. Therapeutics for Inpatients with COVID-19 is a multi-arm, multi-stage platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate antiviral therapeutic agents for adults hospitalized with COVID-19. Five agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed. METHODS: Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. Therapeutics for Inpatients with COVID-19 utilizes a multi-arm, multi-stage design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo, the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and Data and Safety Monitoring Board schedule was developed for the study of potential therapeutic agents with limited in-human data in hospitalized patients with COVID-19. RESULTS: As of 8 August 2021, five agents have entered the Therapeutics for Inpatients with COVID-19 master protocol and a total of 1909 participants have been randomized to one of these agents or matching placebo. There were a number of challenges faced by the study team that needed to be overcome in order to successfully implement Therapeutics for Inpatients with COVID-19 across a global network of sites. These included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff and obtaining regulatory approvals across a global network of sites. CONCLUSION: Through a robust multi-network partnership, the Therapeutics for Inpatients with COVID-19 protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required to achieve the full potential of this approach in dealing with a global outbreak.

Recent advances on Nickel Nano-ferrite: A review on processing techniques, properties and diverse applications

Abstracts Ferrites belong to the wonder class of materials which are known for their wide application range. Among ferrites, spinel ferrites belong to the most promising soft magnetic materials with excellent properties like engineered band gap, high saturation magnetization, coercivity, and better thermal and electrical properties. Among spinel ferrites, Nickel ferrites: a soft, highly magnetic material that exhibit excellent electrical, magnetic, and optical characteristics. Nickel ferrites find their space in a variety of applications because of their unique properties when compared to other ferrite family members. These properties include high saturation magnetisation, less coercivity, high resistivity and permeability. In addition, nanometric Ni ferrites are unique in several properties with modified applications, such as high frequency applications, electronic devices with low loss, biomedical applications, and environmental remedial applications also. This review aim to explore possible synthesis routes, unique properties and diverse applications of Ni ferrite.

Biosynthesis of silver nanospheres, kinetic profiling and their application in the optical sensing of mercury and chlorite ions in aqueous solutions.

Pollution of water linked to microbial decontamination and extensive use of sodium chlorite (NaClO2) as a disinfectant, especially in the face of the current COVID-19 situation, is a serious water pollution issue that needs to be addressed. In this context, an environmentally friendly and cost-effective method has been developed for the biomimetic synthesis of Ag nanospheres (Ag NSs) using aqueous extract of Piper nigrum for the detection of chlorite (ClO2-) and mercury (Hg2+) ions. The strong antioxidant properties of the biomolecules present in the Piper nigrum extract reduce silver ions (Ag+) to Ag0. After optimization of the formulation parameters, it was observed that 1 mL of piper nigrum extract was sufficient to reduce and stabilize 100 mL of 1.5 mM of Ag+ in 2.5 h at 30 °C. X-ray diffraction (XRD) pattern of Ag NSs revealed their crystalline nature and the characteristic Bragg's diffraction peaks confirmed their face cubic crystal (FCC) lattice. The characteristic reddish-brown color and absorption surface plasmon resonance (SPR) band at 435 nm confirmed the successful fabrication of Ag NSs. Kinetic analysis revealed a three-phase growth pattern involving nucleation, growth and stabilization. Transmission electron microscopy (TEM) and High-resolution transmission electron microscopy (HRTEM) micrograms, showed spherical NSs with narrow polydispersity with particle size ranging from 10 to 30 nm. The synthesized NSs were exposed to various metal ions and anions. The absorption intensity of Ag NSs quenched in the presence of mercury ions (Hg2+) among the cations and Chlorite ions (ClO2-) among the anions. The limit of detection (LOD) of 7.47 µM and 1.11 µM was evaluated from the calibration curve for Hg2+ and ClO2-, respectively. Based on these promising results, it is suggested that the method reported is a low-cost and one step biogenic protocol for the synthesis of Ag NSs and their employment for the detection of Hg2+ and ClO2-ions.

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.

BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19. METHODS: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5. RESULTS: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47). CONCLUSIONS: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure. (Funded by Operation Warp Speed and others; TICO ClinicalTrials.gov number, NCT04501978.).

Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).

BACKGROUND: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership initiated the Therapeutics for Inpatients with COVID-19 (TICO). TICO is a multi-arm, multi-stage (MAMS) platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate anti-viral therapeutic agents for adults hospitalized with COVID-19. Four agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed. PROTOCOL DESIGN AND IMPLEMENTATION: Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. TICO utilizes a MAMS design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo as well as the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and DSMB schedule was developed for the study of agents with limited in-human data. CHALLENGES: Challenges included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff, and obtaining regulatory approvals across a global network of sites. CONCLUSION: Through a robust multi-network partnership, the TICO protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required.