SARS-CoV-2: Literature Review Focusing on Structure, Diagnosis and Vaccine Development

SARS-CoV-2 is a highly pathogenic novel ongoing-pandemic virus. It causes COVID-19. Little is known about SARS-CoV-2 biology, countermeasure, and its origin. SARS-CoV-2 is characterized by high infectiousness and sever pathogenesis. COVID-19 crosses the bounders of all continents in a high spreading manner. Here, several aspects regarding the origin and the molecular structure of this novel virus as well as the production of effective vaccines have been addressed. This article illustrated that SARS-CoV-2 was not being recombined inside laboratory and it has a complicated genome that led to sophisticated pathogenesis. Additionally, an important structural protein known as spike S was demonstrated by researchers as an important protein used by the virus for host cell entry as well as for vaccine development. However, the efforts for viral diagnosis and genomic demonstration as well as vaccine production are promising to tackle COVID-19. These perspectives will help in COVID-19 control. However, further investigations are urgently needed to figure out which controlling tactic is more efficient not only in the case of SARS-CoV-2 but also for future pandemics.Copyright © Mohammed Hamzah Abdulkadhim Al-Saadi and Wisam Hindawi Hoidy.

Underpromise and Overdeliver: The Failure of Political Rhetoric in Managing COVID-19 in Australia

From a ‘lucky country' on the edge of the world, Australia and its governments felt they had weathered the pandemic storm in October 2020. But, the insular approach to combatting COVID-19 cracked in the months since. A series of critical failures in government response has been identified. These include vaccine procurement and roll-out, ‘gold standard' contact tracing that turned out abysmal failures, debilitating border closures and an inability to coordinate policy and governance responses to Delta and Omicron variants of SARS-CoV-2. The liberal federal government architecture cracked—some commentators repeatedly use ‘bungled'—under the pressures in this next chapter in Australia's pandemic response. In this chapter, we do not only describe the deficiencies in the federal and state governments' capacity to plan strategically and coordinate between data and intervention, we also show that the resilience of communities is essential in responding to crises—but to grow and thrive, proactive government policies will still be required. © TheEditor(s) (ifapplicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2021, 2022.

Population Index and Analysis Based on Different Geographies, Using Distance Measurement, Social Distancing, and Deep Learning

Nowadays, every individual is familiar with the COVID-19 pandemic which has caused great turmoil in everyone's life. Also, they are aware that there is no medicine or drug to cure COVID immediately, and people are at the risk of losing their lives. Lack of vaccines or delay in vaccine production for mass results social distancing being the only measure to tackle this pandemic. As a result, social distancing has proven to be a very reliable and efficient way to diminish the growth of this disease;the reason why lockdowns are imposed, and people are asked to keep some distance from each other, for their safety as there will be minimal physical contact. Machine learning and artificial intelligence come into the picture in every solution to a generic problem the community faces nowadays like in medical, supply chain management, face detection, etc. Using the power of AI algorithms, the paper aims to develop a robust system to monitor and analyze social distance measurement protocols at public places during the COVID-19 pandemic with the help of CCTV feed and check whether they abide by the safety protocols or not by measuring the distance between them. The proposed approach is implemented to enumerate the number of violations at a popular public place to prevent massive crowds at particular periods. The proposed method is suitable to construct a scrutiny system at a public place to alert people and eschew mass gatherings that can be concluded using achieved results. The paper also has an analysis of the performance of different models of R-CNN, Fast R-CNN, and YOLO. YOLO architectures are validated based on object detection and object tracking rate in real time. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Engineering a Holistic Response to the Global Crisis of Forced Displacement

The global coronavirus pandemic has demonstrated the necessity of engineering approaches, from research and development to rapid prototyping and production, in saving lives all across the world [1]. From personal protective equipment design to vaccine production and distribution, engineering has been the bedrock of an effective global response. However, despite major gains made in the last several decades, there are still millions all across the world, including the vulnerable displaced, who rarely benefit from new developments at the interface of engineering, biology, and health. Copyright © 2010-2012 IEEE.

Renaissance of Equine Antithymocyte Globulin in Renal Transplantation

Introduction: Anti Thymocyte Globulin(ATG) is very effective as an Induction and antirejection therapy (ART) agent in renal Transplantation. Equine ATG (eATG) has been used less compared to rabbit ATG(rATG) in tranplantation. Cost of eATG as induction agent is 200 USD, in comparison to rATG, which costs minimum 700 USD per dose (approximately four times more than eATG). Experience with eATG initially was not good because of drug reactions but over the years the molecule has evolved into a better drug and is the preferred drug over rATG in severe Aplastic Anemia without any reactions. Covid pandemic has affected the supply chain of rATG because of vaccine production leading to shortage of rATG. Hence eATG is the only available ATG. Method(s): We present our experience with eATG in a tertiary care nephrology centre for the last 95 renal transplants. Patients have been divided into two groups. Group A- contained HLA matched first degree relatives as renal donors and induction agent was injection Methylprednisolone (MP). Group B- Had Recipients of Deceased or Spousal donors and received eATG 10mg/kg as induction agent single dose. Monitoring of renal function and observation for complications including, infections was done. Blood lymphocyte count was monitored for intial 2 weeks to look for lymphocyte depletion as an indicator of eATG efficacy. Patients were followed upto 5 years post transplant (PTX) and assessment was done at 1,3 and 5 years for graft and patient survival. eATG usage as anti rejection therapy (ART) agent in acute T- cell-mediated rejection(TCMR) : All acute TCMRs (biopsy proved) were treated with eATG 10mg/kg body for 5 consecutive days followed by repeat biopsy and additional eATG therapy depending on patient response. Result(s): Induction Therapy: Table 1,2,3 Number of recipients in GrA were 41 and GrB were 54. Marked decrease in Lymphocyte count in Gr B indicated efficacy of eATG (p<0.05). In the first 90 days post transplant, Acute TCMR ( biopsy proved) was seen in 5(9.7 %) of GrA and 7(12.9 %) of GrB (p>0.05). In GrA 1(2.4%) patient had acute antibody mediated rejection (ABMR) but could not be treated with ART because of presence of active infection. In Gr B 1(1.8%) patient had histopathological features suggestive of ABMR but was C4D negative and patient responded to eATG alone. Infections were noticed in 9.7% (5/41) of GrA patients and 11.1% (6/54) of GrB patients in the first 180 days PTX (p>0.05). Urinary tract infections, respiratory tract infections and soft tissue infections were commonly seen. Post ART oppurtunistic infections were not seen. Comparison of incidence of Acute rejection rates, graft survival, complications rate and patient survival rate show similar results in both the groups. We achieved good efficacy with eATG as induction and ART agent in biopsy proved acute TCMR. No adverse events and no malignancies were observed after eATG therapy. Conclusion(s): eATG can be used as induction and antirejecton therapy agent in TCMR in renal transplantation. eATG is economical compared to rATG. No conflict of interestCopyright © 2023

SARS-CoV-2 and its Predicted Potential Natural Inhibitors: A Review and Perspective

SARS-CoV-2, a novel coronavirus, has caused the pneumonia outbreak in the entire world and every day, the number of cases is increasing in an exponential manner. Unfortunately, there is no clinically approved drug or vaccine specific for SARS-CoV-2 to date, and analysis of the current rate of spread of infection suggests that there is no time to wait for the approval of drugs and vaccine production. The sequence and phylogenetic analysis of SARS-CoV-2 has shown that it is very much similar to SARS/SARS-like coronaviruses and belongs to the betacoronavirus genera and bats are likely to be the native host of the SARS-CoV-2. Interestingly, the SARS-CoV-2 S protein and SARS-CoV S protein shared an almost identical 3-D structure in the RBD domain and the SARS-CoV-2 S protein was found to have a significant binding affinity to human ACE2. Further, RdRp and 3CLpro protease of SARS-CoV-2 share over 95% of sequence similarity with those of SARS-CoV. Recently, various molecular docking studies have been carried out to search for natural compounds that can target S protein, RdRp, 3CLpro, and nsp proteins of SARS-CoV-2. This review is an attempt to give a comprehensive idea of the different natural products that can be used to target SARS-CoV-2. However, further research is necessary to investigate the potential uses of these predicted SARS-CoV-2 inhibitors in combating the COVID-19 pandemic.Copyright © 2021 Bentham Science Publishers.

The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs.

This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted to the Vaccines Special Issue on the "Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs". To tackle the SARS-CoV-2 pandemic, an acceleration of vaccine development across different technology platforms resulted in the emergency use authorization of multiple vaccines in less than a year. Despite this record speed, many limitations surfaced including unequal access to products and technologies, regulatory hurdles, restrictions on the flow of intellectual property needed to develop and manufacture vaccines, clinical trials challenges, development of vaccines that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, and the distorted allocation of funding to favour dominant companies in affluent countries. Key to future epidemic and pandemic responses will be sustainable, global-public-health-driven vaccine development and manufacturing based on equitable access to platform technologies, decentralised and localised innovation, and multiple developers and manufacturers, especially in low- and middle-income countries (LMICs). There is talk of flexible, modular pandemic preparedness, of technology access pools based on non-exclusive global licensing agreements in exchange for fair compensation, of WHO-supported vaccine technology transfer hubs and spokes, and of the creation of vaccine prototypes ready for phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped by current commercial incentives, the unwillingness of pharmaceutical companies and governments to share intellectual property and know-how, the precariousness of building capacity based solely on COVID-19 vaccines, the focus on large-scale manufacturing capacity rather than small-scale rapid-response innovation to stop outbreaks when and where they occur, and the inability of many resource-limited countries to afford next-generation vaccines for their national vaccine programmes. Once the current high subsidies are gone and interest has waned, sustaining vaccine innovation and manufacturing capability in interpandemic periods will require equitable access to vaccine innovation and manufacturing capabilities in all regions of the world based on many vaccines, not just "pandemic vaccines". Public and philanthropic investments will need to leverage enforceable commitments to share vaccines and critical technology so that countries everywhere can establish and scale up vaccine development and manufacturing capability. This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first.

Vaccine technology transfer in a global health crisis: Actors, capabilities, and institutions.

The COVID-19 pandemic, which featured international pharmaceutical firms seeking to build global manufacturing networks to scale-up the supply of vaccines, has generated heightened interest in understanding the role of firm-to-firm technology transfer. While considerable attention has been given to tracking the extent of international vaccine technology transfer, we know little about how partnerships were established and work in practice. Understanding the challenges that such projects face, and how such challenges may be overcome, is crucially important. This paper provides an account of the partnership between the British-Swedish multinational pharmaceutical company AstraZeneca, the vaccine developer that has engaged in the most technology transfer and built the widest global manufacturing network, and Bio-Manguinhos, a public laboratory linked to Brazil's Ministry of Health. The case study demonstrates the importance of capabilities and regulatory flexibility. Moreover, the analysis highlights the role of political factors that affect the process of technology transfer, and innovation more broadly. Because of the risks involved and the need to quickly mobilize existing capabilities and build new ones, as well as the imperatives of coordinating among manufacturing and regulatory processes and allocating resources to make such arrangements feasible, technology transfer projects need to be enabled politically. Looking forward, the case study has implications for initiatives to expand technology transfer for broadened production of vaccines in the Global South.

Disease X vaccine production and supply chains: risk assessing healthcare systems operating with artificial intelligence and industry 4.0.

Objective: The objective of this theoretical paper is to identify conceptual solutions for securing, predicting, and improving vaccine production and supply chains. Method: The case study, action research, and review method is used with secondary data - publicly available open access data. Results: A set of six algorithmic solutions is presented for resolving vaccine production and supply chain bottlenecks. A different set of algorithmic solutions is presented for forecasting risks during a Disease X event. A new conceptual framework is designed to integrate the emerging solutions in vaccine production and supply chains. The framework is constructed to improve the state-of-the-art by intersecting the previously isolated disciplines of edge computing; cyber-risk analytics; healthcare systems, and AI algorithms. Conclusion: For healthcare systems to cope better during a disease X event than during Covid-19, we need multiple highly specific AI algorithms, targeted for solving specific problems. The proposed framework would reduce production and supply chain risk and complexity in a Disease X event.

Analysis of the COVID-19 virus: Conformation, treatments, and vaccine production

In the year of 2020, COVID-19 pandemic threatened the safety of entire human race. The virus has incredibly strong ability to spread and mutate which quickly spread all over the world and resulted in a perhaps the most serious pandemic in human history. During the early stage of the pandemic there was no viable treatment or antibody, non-pharmaceutical has been carried out trying to contain the spread of the infection. Although right now, some tested vaccines have been distributed in multiple countries, the effectiveness the possible side effects of the vaccine are still waiting to be verified. Mankind still needs a certain amount of time to reach large-scale immunity and may even forever co-exist with this coronavirus. It took the entire world almost a year to develop effective vaccines against this virus. With such developed medical technologies, what makes it so difficult to develop a vaccine against the COVID-19 virus? What kind of virus exactly is COVID-19, and did we sum up any experience from this pandemic to deal with the next possible epidemic more efficiently? This article will explain these problems in a comprehensive and detailed way. © 2022 Author(s).

MANUFACTURING SOLUTIONS - Sterile Drug Product Manufacturing During a Global Pandemic

With vaccines and treatments now available and yet more on the horizon, the first major manufacturing hurdles have been crossed. However, the finish line is still in the distance. As organizations such as drug manufacturers around the world continuously evaluate how to effectively operate, the pandemic has provided a hard reality check. Companies have seen the necessity of strong sourcing/procurement functions to enable business operations. For at least the next few years, we anticipate constraints on aseptic fill/finish and potentially API manufacturing capacity. These constraints can be mitigated by having staffing flexibility when needs arise, enabling rapid technology transfers and adding surge capacity utilization. In addition, truly partnered approaches of pharmaceutical companies and their CDMO suppliers need to be the standard for managing and operating with speed, quality, and safety rigor to meet the needs of the global impact of the pandemic and to ensure focus on the end goal. Finally, maintaining strong relationships with regulatory bodies around the world enables a strong public-private partnership both during and post pandemic, with patients as the shared motivational force to execute and deliver. Copyright © 2021, Drug Delivery Technology. All rights reserved.

A mathematical analysis of the socio-economic impacts of a patent waiver on COVID-19 vaccines

We perform a calibrated mathematical analysis of the potential impacts of a patent waiver on COVID-19 vaccines. In the model, we schematically divide nations into high- and low-income, the latter accounting for 80% of the world population but currently using only 60% of the vaccine production. We show that a significant increase in vaccine production combined with a more equitable distribution - made possible by an intellectual property (IP) waiver - would have stopped the pandemic in 18 months of vaccination and saved more than ten million people, mostly in poor countries, compared with five years of the current scenario in which the virus becomes endemic. We hypothesize the peak rollout capacity shown by high-income countries at the beginning of the vaccination campaign and half of that capacity for low-income ones. We even show that the money saved on vaccines globally in the hypothetical IP-waiver scenario overcomes the actual value of the 5-yr profits of the big pharma in the current situation. This profit loss could be immediately covered (mostly by the expected saving of high-income countries) in exchange for the waiver. © 2022 IEEE.

DEVELOPING VACCINES TO COMBAT HUMAN DISEASES: A HISTORY

This article traces the development of vaccines from the early attempts to combat a fatal disease caused by variola (smallpox) virus in antiquity, through to the highly technical advances which have led to the efficacious vaccines targeting COVID-19. As vaccine preparation has advanced, so has the understanding of the immune response to immunisation and the realisation that the use of adjuvants is essential to boosting the immune response. Furthermore, coupling polysaccharides to proteins is important in achieving vaccine efficacy in young children and older adults. Successful vaccination programmes have led to marked reductions in mortality associated with the diseases targeted by those vaccines – and to the unintended consequence of cultural amnesia regarding those diseases. The anti-vaccination movement has gained traction by riding on this cultural amnesia to capitalise on spurious associations, infrequent public-health disasters around inadvertent administration of faulty vaccine preparations and rare adverse events to build a case against vaccination. This tension between the advances in vaccine production and the criticism cast at the pro-vaccination agenda should be viewed as an agent for growth in the development of safe and effective vaccines, and in the planning to combat future pandemics.

Mobile On Demand COVID-19 Vaccine Production Units for Developing Countries

Two years into the COVID-19 pandemic and more than one year after the approval of the first vaccine, bottlenecks in production and supply chain infrastructure continue to delay vaccination campaigns in the Global South. Mobile on Demand (MOD) vaccine manufacture may help quickly ramp up production capacity while bypassing infrastructure bottlenecks. Such decentralized small-scale factories can help tip the scales in the battle against COVID-19 and future pandemics. In this work, we designed two MOD vaccine manufacturing units based on a protein antigen expressed in yeast and in vitro transcription of mRNA. Each unit consists of three shipping containers and can produce on the order of 10,000 vaccine doses daily for competitive prices and in close proximity of their end users. Abandoning economies of scale may lead to a moderate increase in production costs that may be outweighed by reduced closed-vial dose wastage and an earlier protection of vulnerable populations. © 2022 American Chemical Society.

mRNA Vaccine Technology Transfer and Training Hub in South Africa: A partnership model for sustainable vaccine production

Introduction/ Background: While over 6 billion doses of Covid19 vaccines have been administered globally, only 2% of people in Africa have been vaccinated. This uncomfortable reality lead to the establishment of a mRNA vaccine technology transfer and training Hub in South Africa under the COVAX initiative lead by WHO and MPP. Methods: Afrigen Biologics is establishing a technology transfer and training hub for COVID-19 mRNA-based vaccines. In the absence of a technology transfer agreement with the holders of mRNA vaccine technology, Afrigen and its University partners are developing a firstgeneration vaccine, a fast follow-on of mRNA-1273 (Moderna vaccine). The Afrigen-based vaccine technology transfer program will provide sufficient transfer of know-how to allow a competent tech transfer recipient manufacturer in Africa and other LIMCs to successfully manufacture and release mRNA vaccines at scale to support clinical development, national/regional marketing authorization and WHO prequalification, and sustainable supply to meet local and regional vaccine demand. Results: The mRNA Hub at Afrigen has reached key milestones in terms of completion of the facility and start up phase of equipment supply, training of Afrigen core staff in drug substance and drug product production at lab scale. The development of a stable genetic construct that allows transcription of an mRNA molecule at bench scale as well as the encapsulation in a lipid nano particle is underway. This presentation will provide an overview of the progress of the mRNA Hub, its workplan as well as the long-term research and development program and the partnerships supporting the Hub. Impact: The mRNA vaccine technology transfer Hub has created a public private partnership model for sustainable vaccine manufacturing on the African continent. Supported and enabled by the African Union and the African CDC, the mRNA Hub is well positioned to become one of the pillars of the African vaccine manufacturing strategy. Conclusion: The Covid19 pandemic has unleashed significant energy to ensure that Africa implement programs that will ensure sustainable supply of vaccines and preparedness for future pandemics. The Hub and Spoke model is one of the interventions that has the potential to create local innovation and contribute to the supply of vaccines.

Blockchain-based solution for COVID-19 vaccine waste reduction.

Coronavirus 2019 (COVID-19) vaccines have been produced on a large scale since 2020. However, large-scale vaccine production has led to two forms of waste; namely, overproduction and underutilization. Most of today's systems and technologies used to manage waste data related to COVID-19 vaccines fall short of providing transparency, traceability, accountability, trust, and security features. In this paper, we address the problem of COVID-19 vaccines waste due to their overproduction and underutilization. We propose a blockchain-based solution that is composed of five phases: registration, commitment; production and delivery; consumption; and waste assessment. These phases make up the complete life cycle of a COVID-19 vaccine, and they are governed by several smart contracts to ensure accountability of all the actions taken by the involved entities and reduce any excessive waste caused by overproduction, overordering, or underconsumption. We ensure security, traceability, and data provenance by recording all actions through smart contracts in the form of events on an immutable ledger. We utilize decentralized storage such as the InterPlanetary File System (IPFS) to reduce the costs posed by large-sized file storage when stored on-chain. We present algorithms that describe the logic behind our developed smart contracts. We test and validate the functionalities of our proposed solution. We conduct security, cost, and scalability analyses to show that our solution is affordable, scalable, and secure. We compare our solution with the existing blockchain-based solutions to show its novelty and superiority. The smart contract code is made publicly available on GitHub.

SETTING PRIORITIES IN PUBLIC HEALTH EMERGENCIES: THE PLACE OF TRIAGE IN THE DISTRIBUTION OF COVID-19 VACCINES

Just as it is the case in other issues in clinical ethics, the discourse on COVID-19 has been dominantly preoccupied with the difficulty in taking urgent decision on who gets access to scarce medical resources when demand outstrips supply. The emergence of COVID-19 in the late 2019 and its attendant consequences has created global tension and anxiety. The debate on addressing the ravaging COVID-19 pandemic has gone on at professional and policy levels. It has taken international, intercontinental and inter-racial tones. Critical in this debate are issues of vaccine production, distribution and consumption. Conspiratorial theorists are up in arms against not only the production but also distribution and consumption of the vaccine. The nationalists are taking a hardline posture against free flows of the vaccines across national boundaries while the globalists are pushing for universal access. As this debate continues to inform and enlarge scholarly and policy perspectives, issues of priority in the distribution and consumption still loom large in successes and failures across both the nationalist and globalist paradigms. The nationalists are at the crossroad with respect to prioritizing the distribution and consumption needs of rural dwellers over those of their urban counterparts. The globalists are also confronting priority challenges not only across geographies but also genders. This paper interrogates these dilemmas, with a view to articulating ways in which market and moral dynamics as well as placespecific factors might be mobilized as a game changer in the context of priority in the distribution and consumption of COVID-19 vaccine in Africa. The paper uses conceptual clarification, philosophical argumentation and analysis, to explore the commercial and charity features of the vaccine and demonstrates how some elements within African cosmology may become precursors in the emergence of effective triage system for addressing the nationalist and globalist priority dilemmas in Africa.

The role of vaccines in COVID-19 control strategies in Singapore and China.

Objectives: In this article, we critically review the development and implementation of COVID-19 vaccination in Singapore and China during the pandemic. Methods: We collect and analyze data from a range of sources, including scholarly articles, statistics and documents from national governments in the two countries, and reports from international organizations. Results: There are important differences in the two countries' approaches to the evolving pandemic, and thus the roles that COVID-19 vaccination plays in the overall response strategies in these two countries. Conclusions: Whereas Singapore adopted a "living with the virus" strategy, China continued to pursue a COVID-zero strategy. The overall COVID-19 response strategy of Singapore was largely shared by many countries in the world, while that of China was more unique and hardly imitated elsewhere. Nevertheless, vaccination played a significant role in both countries' responses to the pandemic. A comparison and contrast between the vaccination processes in these two countries thus shed important light on the drivers and outcomes of COVID-19 vaccination in different settings.