Production-sharing of critical resources with dynamic demand under pandemic situation: The COVID-19 pandemic.

The COVID-19 virus's high transmissibility has resulted in the virus's rapid spread throughout the world, which has brought several repercussions, ranging from a lack of sanitary and medical products to the collapse of medical systems. Hence, governments attempt to re-plan the production of medical products and reallocate limited health resources to combat the pandemic. This paper addresses a multi-period production-inventory-sharing problem (PISP) to overcome such a circumstance, considering two consumable and reusable products. We introduce a new formulation to decide on production, inventory, delivery, and sharing quantities. The sharing will depend on net supply balance, allowable demand overload, unmet demand, and the reuse cycle of reusable products. Undeniably, the dynamic demand for products during pandemic situations must be reflected effectively in addressing the multi-period PISP. A bespoke compartmental susceptible-exposed-infectious-hospitalized-recovered-susceptible (SEIHRS) epidemiological model with a control policy is proposed, which also accounts for the influence of people's behavioral response as a result of the knowledge of adequate precautions. An accelerated Benders decomposition-based algorithm with tailored valid inequalities is offered to solve the model. Finally, we consider a realistic case study - the COVID-19 pandemic in France - to examine the computational proficiency of the decomposition method. The computational results reveal that the proposed decomposition method coupled with effective valid inequalities can solve large-sized test problems in a reasonable computational time and 9.88 times faster than the commercial Gurobi solver. Moreover, the sharing mechanism reduces the total cost of the system and the unmet demand on the average up to 32.98% and 20.96%, respectively.

Fair-Split Distribution of Multi-dose Vaccines with Prioritized Age Groups and Dynamic Demand: The case study of COVID-19

The emergence of the SARS-CoV-2 virus and new viral variations with higher transmission and mortality rates have highlighted the urgency to accelerate vaccination to mitigate the morbidity and mortality of the COVID-19 pandemic. For this purpose, this paper formulates a new multi-vaccine, multi-depot location-inventory-routing problem for vaccine distribution. The proposed model addresses a wide variety of vaccination concerns: prioritizing age groups, fair distribution, multi-dose injection, dynamic demand, etc. To solve large-size instances of the model, we employ a Benders decomposition algorithm with a number of acceleration techniques. To monitor the dynamic demand of vaccines, we propose a new adjusted susceptible-infectious-recovered (SIR) epidemiological model, where infected individuals are tested and quarantined. The solution to the optimal control problem dynamically allocates the vaccine demand to reach the endemic equilibrium point. Finally, to illustrate the applicability and performance of the proposed model and solution approach, the paper reports extensive numerical experiments on a real case study of the vaccination campaign in France. The computational results show that the proposed Benders decomposition algorithm is 12 times faster, and its solutions are, on average, 16% better in terms of quality than the Gurobi solver under a limited CPU time. In terms of vaccination strategies, our results suggest that delaying the recommended time interval between doses of injection by a factor of 1.5 reduces the unmet demand up to 50%. Furthermore, we observed that the mortality is a convex function of fairness and an appropriate level of fairness should be adapted through the vaccination.

Isolation, characterization, therapeutic potency, and genomic analysis of a novel bacteriophage vB_KshKPC-M against carbapenemase-producing Klebsiella pneumoniae strains (CRKP) isolated from Ventilator-associated pneumoniae (VAP) infection of COVID-19 patients.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant clinical problem, given the lack of therapeutic options. The CRKP strains have emerged as an essential worldwide healthcare issue during the last 10 years. Global expansion of the CRKP has made it a significant public health hazard. We must consider to novel therapeutic techniques. Bacteriophages are potent restorative cases against infections with multiple drug-resistant bacteria. The Phages offer promising prospects for the treatment of CRKP infections. OBJECTIVE: In this study, a novel K. pneumoniae phage vB_KshKPC-M was isolated, characterized, and sequenced, which was able to infect and lyse Carbapenem-resistant K. pneumoniae host specifically. METHODS: One hundred clinical isolates of K. pneumoniae were collected from patients with COVID-19 associated with ventilator-associated acute pneumonia hospitalized at Shahid Beheshti Hospital, Kashan, Iran, from 2020 to 2021. Initially, all samples were cultured, and bacterial isolates identified by conventional biochemical tests, and then the ureD gene was used by PCR to confirm the isolates. The Antibiotic susceptibility test in the disc diffusion method and Minimum inhibitory concentrations for Colistin was done and interpreted according to guidelines. Phenotypic and molecular methods determined the Carbapenem resistance of isolates. The blaKPC, blaNDM, and blaOXA-23 genes were amplified for this detection. Biofilm determination of CRKP isolates was performed using a quantitative microtiter plate (MTP) method. The phage was isolated from wastewater during the summer season at a specific position from Beheshti Hospital (Kashan, Iran). The sample was processed and purified against the bacterial host, a CRKP strain isolated from a patient suffering from COVID-19 pneumoniae and resistance to Colistin with high potency for biofilm production. This isolate is called Kp100. The separated phages were diluted and titration by the double overlay agar plaque assay. The separate Phage is concentrated with 10% PEG and stored at -80 °C until use. The phage host range was identified by the spot test method. The purified phage morphology was determined using a transmission electron microscope. The phage stability tests (pH and temperature) were analyzed. The effect of cationic ions on phage adsorption was evaluated. The optimal titer of bacteriophage was determined to reduce the concentration of the CRKP strain. One-step growth assays were performed to identify the purified phage burst's latent cycle and size. The SDS-PAGE was used for phage proteins analysis. Phage DNA was extracted by chloroform technique, and the whole genome of lytic phage was sequenced using Illumina HiSeq technology (Illumina, San Diego, CA). For quality assurance and preprocessing, such as trimming, Geneious Prime 2021.2.2 and Spades 3.9.0. The whole genome sequence of the lytic phage is linked to the GenBank database accession number. RASTtk-v1.073 was used to predict and annotate the ORFs. Prediction of ORF was performed using PHASTER software. ResFinder is used to assess the presence of antimicrobial resistance and virulence genes in the genome. The tRNAs can-SE v2.0.6 is used to determine the presence of tRNA in the genome. Linear genome comparisons of phages and visualization of coding regions were performed using Easyfig 2.2.3 and Mauve 2.4.0. Phage lifestyles were predicted using the program PHACTS. Phylogenetic analysis and amino acid sequences of phage core proteins, such as the major capsid protein. Phylogenies were reconstructed using the Neighbor-Joining method with 1000 bootstrap repeat. HHpred software was used to predict depolymerase. In this study, GraphPad Prism version 9.1 was used for the statistical analysis. Student's t-test was used to compare the sets and the control sets, and the significance level was set at P ≤ 0.05. RESULTS: Phage vB_KshKPC-M is assigned to the Siphoviridae, order Caudovirales. It was identified as a linear double-stranded DNA phage of 54,378 bp with 50.08% G + C content, had a relatively broad host range (97.7%), a short latency of 20 min, and a high burst size of 260 PFU/cell, and was maintained stable at different pH (3-11) and temperature (45-65 °C). The vB_KshKPC-M genome contains 91 open-reading frames. No tRNA, antibiotic resistance, toxin, virulence-related genes, or lysogen-forming gene clusters were detected in the phage genome. Comparative genomic analysis revealed that phage vB_KshKPC-M has sequence similarity to the Klebsiella phages, phage 13 (NC_049844.1), phage Sushi (NC_028774.1), phage vB_KpnD_PeteCarol (OL539448.1) and phage PWKp14 (MZ634345.1). CONCLUSION: The broad host range and antibacterial activity make it a promising candidate for future phage therapy applications. The isolated phage was able to lyse most of the antibiotic-resistant clinical isolates. Therefore, this phage can be used alone or as a phage mixture in future studies to control and inhibit respiratory infections caused by these bacteria, especially in treating respiratory infections caused by resistant strains in sick patients.

2019 Novel coronavirus (COVID-19) overview.

Novel coronaviruses (CoVs) are zoonotic pathogens, but the first human-to-human transmission has been reported. CoVs have the best known genome of all RNA viruses, and mutations in the genome have now been found. A pneumonia of unknown cause detected in Wuhan, China, was first reported to the WHO Country Office in China on 31 December 2019. This study aims to report early findings related to COVID-19 and provide methods to prevent and treat it.

Bi-objective optimization of a stochastic resilient vaccine distribution network in the context of the COVID-19 pandemic.

This paper develops an approach to optimize a vaccine distribution network design through a mixed-integer nonlinear programming model with two objectives: minimizing the total expected number of deaths among the population and minimizing the total distribution cost of the vaccination campaign. Additionally, we assume that a set of input parameters (e.g., death rate, social contacts, vaccine supply, etc.) is uncertain, and the distribution network is exposed to disruptions. We then investigate the resilience of the distribution network through a scenario-based robust-stochastic optimization approach. The proposed model is linearized and finally validated through a real case study of the COVID-19 vaccination campaign in France. We show that the current vaccination strategies are not optimal, and vaccination prioritization among the population and the equity of vaccine distribution depend on other factors than those conceived by health policymakers. Furthermore, we demonstrate that a vaccination strategy mixing the population prioritization and the quarantine restrictions leads to an 8.5% decrease in the total number of deaths.

Assessment of BIV1-CovIran inactivated vaccine-elicited neutralizing antibody against the emerging SARS-CoV-2 variants of concern.

OBJECTIVES: The BIV1-CovIran vaccine is highly effective against COVID-19. The neutralizing potency of all SARS-CoV-2 vaccines seems to be decreased against variants of concern. We assessed the sensitivity of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants to neutralizing antibodies (NAbs) present in sera from individuals who had received the BIV1-CovIran candidate vaccine compared with an original Wuhan-related strain. METHODS: The ability of vaccine serum to neutralize the variants was measured using the conventional virus neutralization test. The correlation of spike (S) protein antibody and anti-receptor binding domain with neutralizing activity was investigated. RESULTS: The current study demonstrated that 29 of 32 (90.6%; 95% CI: 75.0-98.0) of the vaccinees developed NAbs against a Wuhan-related strain. It is noteworthy that 28 (87.50%) and 24 of 32 (75%) of the recipients were able to produce NAbs against Alpha, Beta, and Delta variants, respectively. Serum virus-neutralizing titres for different SARS-CoV-2 strains were weakly correlated with anti-receptor binding domain antibodies (Spearman r = 36-42, p < 0.05), but not S-binding antibodies (p > 0.05). DISCUSSION: Although there was a reduction in neutralization titres against the Alpha, Beta, and Delta variants compared with the Wuhan strain, BIV1-CovIran still exhibited potent neutralizing activity against the SARS-CoV-2 variants of concern.

2019 Novel coronavirus (COVID-19) overview

Novel coronaviruses (CoVs) are zoonotic pathogens, but the first human-to-human transmission has been reported. CoVs have the best known genome of all RNA viruses, and mutations in the genome have now been found. A pneumonia of unknown cause detected in Wuhan, China, was first reported to the WHO Country Office in China on 31 December 2019. This study aims to report early findings related to COVID-19 and provide methods to prevent and treat it.

The impact of spike mutated variants of SARS-CoV2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines.

Since the first described human infection with SARS-CoV-2 in December of 2019 many subunit protein vaccines have been proposed for use in humans. Subunit vaccines use one or more antigens suitable for eliciting a robust immune response. However, the major concern is the efficacy of subunit vaccines and elicited antibodies to neutralize the variants of SARS-CoV-2 like B.1.1.7 (Alpha), B.1.351 (Beta) and P1 (Gamma), B.1.617 (Delta) and C.37 (Lambda). The Spike protein (S) is a potential fragment for use as an antigen in vaccine development. This protein plays a crucial role in the first step of the infection process, as it binds to Angiotensin-Converting Enzyme 2 (ACE2) receptor and enters the host cell after binding. Immunization-induced specific antibodies against the receptor binding domain (RBD) may block and effectively prevent virus invasion. The focus of this review is the impact of spike mutated variants of SARS-CoV2 (Alpha, Beta, Gamma, Delta, and Lambda) on the efficacy of subunit recombinant vaccines. To date, a low or no significant impact on vaccine efficacy against Alpha and Delta variants has been reported. Such an impact on vaccine efficacy for Beta, Delta, Gamma, and Lambda variants may be even greater compared to the Alpha variant. Nonetheless, more comprehensive analyses are needed to assess the real impact on vaccine efficacy brought about by SARS-CoV-2 variants.

Garlic (Allium sativum L.): a potential unique therapeutic food rich in organosulfur and flavonoid compounds to fight with COVID-19.

Coronavirus disease 2019 (COVID-19) is the current major health crisis in the world. A successful strategy to combat the COVID-19 pandemic is the improvement of nutritional pattern. Garlic is one of the most efficient natural antibiotics against the wide spectrum of viruses and bacteria. Organosulfur (e.g., allicin and alliin) and flavonoid (e.g., quercetin) compounds are responsible for immunomodulatory effects of this healthy spice. The viral replication process is accelerated with the main structural protease of SARS-CoV-2. The formation of hydrogen bonds between this serine-type protease and garlic bioactives in the active site regions inhibits the COVID-19 outbreak. The daily dietary intake of garlic and its derived-products as an adjuvant therapy may improve side effects and toxicity of the main therapeutic drugs with reducing the used dose.