Current advances in novel SARS-CoV-2 disease (COVID-19) treatment and intervention strategies

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Mohammad Khalid Parvez ◽  
Kartika Padhan
Keyword(s):  
Clinical Trials ◽  
Ebola Virus ◽  
Management Strategies ◽  
Intervention Strategies ◽  
Phase Iii ◽  
World Health ◽  
Plasma Therapy ◽  
Health Crisis ◽  
Vaccine Candidates ◽  
Poor Countries

Background: Down the seven months of the novel SARS-CoV-2 disease (COVID-19) outbreak in China and its global spread, there is a remarkable understanding of its epidemiology, pathobiology and clinical management strategies. While countering a heavy toll on health and economy, world’s regional authorities are enforcing safety guidelines and providing patient care. Currently, there is no globally approved treatment or intervention for COVID-19. Methods: A structured online literature search for peer-reviewed articles was conducted on the PubMed, Europe PMC, Google, WHO, CDC, FDA and ClinicalTrials portals, using phrases such as COVID-19 treatment and intervention, COVID-19 drugs and COVID-19 vaccines. Results: Analysis of the retrieved data showed that as a part of ‘Solidarity Clinical Trials’, hundreds of treatment and intervention strategies, including antiviral drugs, cytokine antagonists, convalescent plasma therapy and vaccine candidates have been registered, worldwide. Of these, while remdesivir the anti-Ebola virus drug has been granted approval as ‘emergency use’ drug in USA, favipiravir, the anti-flu drug has been recently approved in Russia. Tocilizumab and sarilumab, the cytokine (IL-6) antagonists have entered Phase-II/III clinical trials in hospitalized COVID-19 patients. Among the leading vaccine candidates, an mRNA-1273 vaccine along with Pfizer mRNA candidate and Oxford ChAdOx1vaccine have entered Phase-III trial. Conclusion: The world health authorities have strongly and quickly responded to COVID-19 pandemic. Nonetheless, it is imperative for world bodies to unite in combating this health crisis by developing costeffective drugs and vaccines, and making them accessible to resource-poor countries.

Efficacy and Safety of AZD1222, BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2

2021 ◽  
Vol 5 (1) ◽  
pp. 791-796
Author(s):  
Ilir Alimehmeti
Keyword(s):  
Clinical Trials ◽  
Diagnostic Tests ◽  
Web Of Science ◽  
Rapid Development ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Vaccine Candidates ◽  
Genetic Sequence ◽  
Phase Iii Clinical Trials ◽  
Clinical Trial Results

SARS-CoV-2, the beta coronavirus causing COVID-19, was isolated and categorizes as a novel one on January 7th, 2020 in China.[1] To date, official reports depict that SARS-CoV-2 has already infected 88.828.387 persons and caused 1.926.625 deaths worldwide.[2] On January 12th, 2020, China officials made public its genetic sequence, thus paving the way towards the research and development of diagnostic tests and vaccines. With regard to vaccination, e large number of clinical trials were designed and are currently undergoing, of which 189 are listed in ClinicalTrials.gov. [3] However, up to date, only three vaccines have published their respective phase III clinical trial results in peer-reviewed medical journals. [4-6] Vaccines are needed to reduce the morbidity and mortality associated with Covid-19, and multiple vaccine platforms as AZD1222 (AstraZeneca) [4], BNT162b2 (Pfizer/BioNTech) [5] and mRNA-1273 (Moderna) have been involved in the rapid development of vaccine candidates. Methodology: In this review, PubMed, Embase, Web of Science, Scopus, medRxiv, and bioRxiv were systematically scrutinized for peer-reviewed and preprint articles on phase III clinical trials of vaccines against SARS-CoV-2. In total, only three peer-reviewed papers fulfilling the search criteria were identified. Conclusions; All vaccine candidates should publish in peer-reviewed journals their efficacy and safety well before requesting approval to the national or international authorities…

scholarly journals Self-Replicating RNA Viruses for RNA Therapeutics

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3310 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Antibody Responses ◽  
Phase Iii ◽  
Phase I Clinical Trials

Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans.

scholarly journals Developmental Landscape of Potential Vaccine Candidates Based on Viral Vector for Prophylaxis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Rajashri Bezbaruah ◽  
Pobitra Borah ◽  
Bibhuti Bhushan Kakoti ◽  
Nizar A. Al-Shar’I ◽  
Balakumar Chandrasekaran ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Viral Vector ◽  
World Health ◽  
Prolonged Incubation ◽  
Vaccine Candidates ◽  
Vector Vaccine ◽  
Dna And Rna ◽  
Viral Vector Vaccine

Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, arose at the end of 2019 as a zoonotic virus, which is the causative agent of the novel coronavirus outbreak COVID-19. Without any clear indications of abatement, the disease has become a major healthcare threat across the globe, owing to prolonged incubation period, high prevalence, and absence of existing drugs or vaccines. Development of COVID-19 vaccine is being considered as the most efficient strategy to curtail the ongoing pandemic. Following publication of genetic sequence of SARS-CoV-2, globally extensive research and development work has been in progress to develop a vaccine against the disease. The use of genetic engineering, recombinant technologies, and other computational tools has led to the expansion of several promising vaccine candidates. The range of technology platforms being evaluated, including virus-like particles, peptides, nucleic acid (DNA and RNA), recombinant proteins, inactivated virus, live attenuated viruses, and viral vectors (replicating and non-replicating) approaches, are striking features of the vaccine development strategies. Viral vectors, the next-generation vaccine platforms, provide a convenient method for delivering vaccine antigens into the host cell to induce antigenic proteins which can be tailored to arouse an assortment of immune responses, as evident from the success of smallpox vaccine and Ervebo vaccine against Ebola virus. As per the World Health Organization, till January 22, 2021, 14 viral vector vaccine candidates are under clinical development including 10 nonreplicating and four replicating types. Moreover, another 39 candidates based on viral vector platform are under preclinical evaluation. This review will outline the current developmental landscape and discuss issues that remain critical to the success or failure of viral vector vaccine candidates against COVID-19.

scholarly journals Safety and efficacy of RNA vaccines: State of the art

2021 ◽  
Vol 23 (5) ◽  
pp. 1017-1030
Author(s):  
A. V. Blagov ◽  
A. A. Bukaeva ◽  
V. V. Makarov ◽  
Z. V. Bochkaeva
Keyword(s):  
Clinical Trials ◽  
Ebola Virus ◽  
Viral Infections ◽  
Phase Iii ◽  
Protective Properties ◽  
Market Launch ◽  
The World ◽  
Mass Immunization ◽  
First Results ◽  
The Moment

This review describes principles of action and the method of delivery of mRNA molecules into cells, as well as some of developed RNA vaccines and the results obtained in their study, though they have not been authorized for use yet. In addition, the review discusses efficacy and safety proved for RNA vaccines registered for COVID-19 prevention at the time of writing. The development, clinical trials and market launch of RNA vaccines for mass immunization in a few months can be considered one of the major breakthroughs in pharmacology over the past year. Despite of all seemingly indisputable advantages, none of RNA vaccines had reached Phase III of clinical trials since the moment of its discovery in 1993 until last year. The first experience of the successful use of mRNA vaccines was back in the 90s of the last century, when vaccination of mice with liposomes encoding an antigen-encoding mRNA was found to initiate specific immune response in mice. However, in these years, the method did not find application, due to the toxicity of lipids used. Subsequently, a large number of attempts have been made to develop vaccines against other viral infections, including Zika virus, Dengue virus, Ebola virus, cytomegalovirus, influenza virus and others. Despite the importance for preventing the spread of these diseases, the development of a vaccine preparation is a rather lengthy process, and final success is not guaranteed. However, the COVID-19 pandemic has become speeded the development of mRNA vaccines up.At the time of writing the review, two mRNA-based vaccines have been registered only in the world, both, BNT162b2 and mRNA-1273, were against COVID-19. Their effectiveness and safety are still actively studied. Moreover, it took less than a year for new strains of SARS-CoV-2 to appear, and the efficiency of vaccines against them was found to be lower than against the reference pathogen variant. Considering that the three new strains of SARS-CoV-2, “British”, “African” and “Brazilian”, are rapidly spreading in the world, the first results of efficiency evaluation of vaccines against them have already been published. One may expect that, considering mutations in these strains, the BNT162b2 and mRNA-1273 vaccines will remain effective against the “British” strain, but their protective properties are greatly weakened against the “African” variant.

scholarly journals PROSPECTS OF SARS-CoV-2 VACCINES AND THEIR LANDSCAPE

2020 ◽  
Vol 8 (Spl-1-SARS-CoV-2) ◽  
pp. S246-S263
Author(s):  
Bharti Kotarya ◽  
◽  
Abhishek Pandeya ◽  
Raj Kumar Khalko ◽  
Anup Mishra ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Nucleic Acid ◽  
Viral Vectors ◽  
Age Groups ◽  
World Health ◽  
Current Status ◽  
Vaccine Production ◽  
Vaccine Candidates ◽  
The World ◽  
Effective Drugs

Severe Acute Respiratory Syndrome Corona Virus -2 (SARS-CoV-2), puzzled the whole world with its diverse, unique clinical spectrum, and unprecedented transmission dynamics. The disease caused by this virus is named as Coronavirus disease-19 (COVID-19), reported first time in Wuhan, China, in December 2019. It had spread to almost all countries of the world disrupting the health and economy of many countries. It was the recent zoonotic spillover disease reported in humans from the Coronavirus group, without proper medicine and non-existence of prior immunity, this disease posed a challenge to both the scientific and medical fraternity. The search for safe, effective drugs to treat the disease and vaccines against the causative agent SARS- CoV-2 had begun all over the world with public and private partnerships. Many countries are part of the solidarity trail for identifying the effective drugs, clinical trials and vaccines for this global pandemic. Here in this review, we are focussing on the different vaccine production platforms being used in the preparation of vaccines against SARS-CoV-2, their current status and prospects. Vaccine production technology significantly advanced in recent times by imbibing the cutting edge technologies such as nucleic acid based technologies such as DNA/RNA/Codon deoptimization and availability of safe and effective viral vectors produced through rDNA technology. The availability of complete genome sequence of SARS-CoV-2, geared up for the production of vaccine candidates based on these new vaccine production platforms, and in a record time of 4-5 months, these vaccine candidates entered in human clinical trials for the evaluation of safety and efficacy. Prior knowledge on SARS and MERS-CoV’s structural and genomic features, vaccine production platforms used in making vaccines against them greatly augmented in the SARS-CoV-2 vaccine efforts. As per World Health Organization (WHO) a total of202 vaccine candidates are under developing for SARS-CoV-2, among them 47 entered in clinical trials and 156 are in the preclinical stage. These vaccines are prepared by an amalgamation of both new and old traditional vaccine production platforms such as nucleic acid base platforms, inactivated, live attenuated, recombinant viral vectors, protein and peptide-based vaccines. The success of these vaccine candidates lies in the generation of effective immune response for SARS-CoV-2 across all age groups and people with co-morbidities. We briefly summarize the different strategies of SARS-CoV-2 vaccine production and their prospects with an emphasis on different routes of administration and added a basic mathematical model depicting the importance of vaccination for any pandemic.

scholarly journals The Rationale for Potential Pharmacotherapy of COVID-19

2020 ◽  
Vol 13 (5) ◽  
pp. 96 ◽  
Author(s):  
Maha Saber-Ayad ◽  
Mohamed A. Saleh ◽  
Eman Abu-Gharbieh
Keyword(s):  
Clinical Trials ◽  
Health Care Professionals ◽  
Large Scale ◽  
Clinical Care ◽  
Management Strategies ◽  
Standard Of Care ◽  
World Health ◽  
High Morbidity ◽  
Human Coronavirus ◽  
The World

On 11 March 2020, the coronavirus disease (COVID-19) was defined by the World Health Organization as a pandemic. Severe acute respiratory syndrome-2 (SARS-CoV-2) is the newly evolving human coronavirus infection that causes COVID-19, and it first appeared in Wuhan, China in December 2019 and spread rapidly all over the world. COVID-19 is being increasingly investigated through virology, epidemiology, and clinical management strategies. There is currently no established consensus on the standard of care in the pharmacological treatment of COVID-19 patients. However, certain medications suggested for other diseases have been shown to be potentially effective for treating this infection, though there has yet to be clear evidence. Therapies include new agents that are currently tested in several clinical trials, in addition to other medications that have been repurposed as antiviral and immune-modulating therapies. Previous high-morbidity human coronavirus epidemics such as the 2003 SARS-CoV and the 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) prompted the identification of compounds that could theoretically be active against the emerging coronavirus SARS-CoV-2. Moreover, advances in molecular biology techniques and computational analysis have allowed for the better recognition of the virus structure and the quicker screening of chemical libraries to suggest potential therapies. This review aims to summarize rationalized pharmacotherapy considerations in COVID-19 patients in order to serve as a tool for health care professionals at the forefront of clinical care during this pandemic. All the reviewed therapies require either additional drug development or randomized large-scale clinical trials to be justified for clinical use.

scholarly journals SARS-CoV-2: Immune Response Elicited by Infection and Development of Vaccines and Treatments

2020 ◽  
Vol 11 ◽  
Author(s):  
Gisela Canedo-Marroquín ◽  
Farides Saavedra ◽  
Catalina A. Andrade ◽  
Roslye V. Berrios ◽  
Linmar Rodríguez-Guilarte ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Clinical Manifestations ◽  
Antibody Therapy ◽  
Phase Iii ◽  
World Health ◽  
Proinflammatory Mediators ◽  
Major Player ◽  
Health Organization ◽  
In The Beginning

The World Health Organization (WHO) announced in March a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This new infectious disease was named Coronavirus Disease 19 (COVID-19), and at October 2020, more than 39,000,000 cases of SARS-CoV-2 have been detected worldwide leading to near 1,100,000 deaths. Clinically, COVID-19 is characterized by clinical manifestations, such as fever, dry cough, headache, and in more severe cases, respiratory distress. Moreover, neurological-, cardiac-, and renal-related symptoms have also been described. Clinical evidence suggests that migration of immune cells to the affected organs can produce an exacerbated release of proinflammatory mediators that contribute to disease and render the immune response as a major player during the development of the COVID-19 disease. Due to the current sanitary situation, the development of vaccines is imperative. Up to the date, 42 prototypes are being tested in humans in different clinical stages, with 10 vaccine candidates undergoing evaluation in phase III clinical trials. In the same way, the search for an effective treatment to approach the most severe cases is also in constant advancement. Several potential therapies have been tested since COVID-19 was described, including antivirals, antiparasitic and immune modulators. Recently, clinical trials with hydroxychloroquine—a promising drug in the beginning—were suspended. In addition, the Food and Drug Administration (FDA) approved convalescent serum administration as a treatment for SARS-CoV-2 patients. Moreover, monoclonal antibody therapy is also under development to neutralize the virus and prevent infection. In this article, we describe the clinical manifestations and the immunological information available about COVID-19 disease. Furthermore, we discuss current therapies under study and the development of vaccines to prevent this disease.

scholarly journals Sex Differences in Immunity: Implications for the Development of Novel Vaccines Against Emerging Pathogens

2021 ◽  
Vol 11 ◽  
Author(s):  
Anahita Fathi ◽  
Marylyn M. Addo ◽  
Christine Dahlke
Keyword(s):  
Clinical Trials ◽  
Sex Differences ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Virus Disease ◽  
Emerging Infectious Diseases ◽  
Vaccine Safety ◽  
Emerging Infections ◽  
Emerging Pathogens ◽  
Vaccine Candidates

Vaccines are one of the greatest public health achievements and have saved millions of lives. They represent a key countermeasure to limit epidemics caused by emerging infectious diseases. The Ebola virus disease crisis in West Africa dramatically revealed the need for a rapid and strategic development of vaccines to effectively control outbreaks. Seven years later, in light of the SARS-CoV-2 pandemic, this need has never been as urgent as it is today. Vaccine development and implementation of clinical trials have been greatly accelerated, but still lack strategic design and evaluation. Responses to vaccination can vary widely across individuals based on factors like age, microbiome, co-morbidities and sex. The latter aspect has received more and more attention in recent years and a growing body of data provide evidence that sex-specific effects may lead to different outcomes of vaccine safety and efficacy. As these differences might have a significant impact on the resulting optimal vaccine regimen, sex-based differences should already be considered and investigated in pre-clinical and clinical trials. In this Review, we will highlight the clinical observations of sex-specific differences in response to vaccination, delineate sex differences in immune mechanisms, and will discuss the possible resulting implications for development of vaccine candidates against emerging infections. As multiple vaccine candidates against COVID-19 that target the same antigen are tested, vaccine development may undergo a decisive change, since we now have the opportunity to better understand mechanisms that influence vaccine-induced reactogenicity and effectiveness of different vaccines.

scholarly journals COVID-19: Understanding the Pandemic Emergence, Impact and Infection Prevalence Worldwide

2020 ◽  
Vol 14 (4) ◽  
pp. 2235-2251
Author(s):  
Priyadarshini Dey ◽  
S. Vaijayanthimala ◽  
Vivek S. Dalvi ◽  
Ashu Jain ◽  
Deepak Gola ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Global Economy ◽  
Severe Pneumonia ◽  
Phase Iii ◽  
World Health ◽  
Diagnostic Tools ◽  
Viral Gene ◽  
Infection Prevalence ◽  
Human Antibody ◽  
Plasma Therapy

Coronavirus disease (COVID-19) has showed high transmission across the continents due to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) with total infected cases of around ~ 44 million people. This communicable virus that initiated from the Wuhan city of China in the month of December 2020 has now spread to 189 different countries with 1.1 million fatalities worldwide (till 28 Oct, 2020). The World Health Organization (WHO) declared this outbreak as Public Health Emergency of International Concern in January, 2020. The infection spreads mainly due to contact with infected droplets or fomites, highlighting flu like symptoms initially, which may further progress into severe pneumonia and respiratory failure, often observed in elderly patients with prehistory of other diseases. The diagnosis is based on detection of viral antigen, human antibody and viral gene (RT-PCR). Further, various other diagnostic tools including X-ray, CT-scan are used for imaging purpose, recently artificial intelligence based imaging (contactless scanning) gained popularity. Generally testing of existing drugs (repurposing) and development of new molecules are the main strategies adopted by researchers. However, as per initial findings, various drugs, monoclonal antibody and plasma therapy were found to show effectiveness against COVID-19. Further, many vaccine candidates have entered or will soon enter phase III clinical testing. This disease has further challenged the global economy. Thus, this review uniquely compares the strategies adopted by developed and developing countries worldwide including protective measures like lockdown, continuous testing, utilizing latest tools (artificial intelligence) in curbing this infection spread.

Immunogenicity and Safety Profile of COVID-19 Vaccines- A Systematic Review (Preprint)

2020 ◽  
Author(s):  
Reeju Maharjan ◽  
Aditya Bamboria ◽  
Neelam Asghar ◽  
Manish Shrestha ◽  
Syed W H Rizvi
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Systematic Reviews ◽  
Neutralizing Antibodies ◽  
Phase Iii ◽  
Effective Vaccine ◽  
Efficacy And Safety ◽  
Vaccine Candidates ◽  
One Year ◽  
Meta Analyses

BACKGROUND An effective vaccine will be important in controlling severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. OBJECTIVE In this study, we aim to analyze the degree of immunogenicity that rises after administering different vaccines, and to study their efficacy. METHODS We systematically reviewed multiple vaccine candidates at different stages of clinical trials to prevent Coronavirus disease in 2019 (COVID-19). We reviewed literature from four major electronic databases (PubMed, MEDLINE, PubMed Central, and Google scholar) to identify studies on SARS-CoV-2 vaccine candidates. This article included studies that include clinical trials in multiple stages and systematic reviews published in 2020. We performed a quality assessment with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for our articles. RESULTS We included a total of 19 articles. This review article has a total of 24,342 individuals. These studies show promising results regarding vaccines candidates, safety profiles, and immunogenicity with the effective generation of neutralizing antibodies and specific T-cell responses. Adverse effects range from mild to moderate, with no serious adverse effects reported. It is unclear how long the generated immunity will last, and a follow up of the study participants for an extended one-year period will be needed. CONCLUSIONS Ascertaining vaccines' efficacy and safety in vulnerable populations is essential for the general use of vaccine use. A number of these vaccines are currently under phase III or to enter phase III and may increase vaccines' efficacy and safety in different populations.

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