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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic, reaching almost one million death worldwide. At present standard treatment for coronavirus disease 2019 (COVID-19) is not well defined because the evidence, either from randomized or observational studies, with conflicting results, has led to rapid changes in treatment guidelines. Our aim was to narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and interpretation of the data by experts who are treating patients in the frontline setting. The panel conducted a detailed review of the literature and eventual press releases from randomized clinical trials for each possible available treatment. Inductive PubMed search waws performed for publications relevant to the topic, including all clinical trials conducted. The result was a flowchart with treatment indications for patients with COVID-19. After 6 months of a pandemic situation and before a possible second coronavirus wave descends on Europe, it is important to evaluate which drugs proved to be effective while also considering that results from many randomized clinical trials are still awaited. Indeed, among treatments for COVID-19, only glucocorticoids have resulted in an association with a significant decrease in mortality in published randomized controlled trials. New therapeutic strategies are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID‐19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type‐2 (T2) inflammation endotypes. Methods: The current knowledge on COVID‐19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. Results: Based on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID‐19 pandemic. Conclusion: Intranasal corticosteroids remain the standard treatment for CRS in patients with SARS‐CoV‐2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID‐19 infection. [ABSTRACT FROM AUTHOR]

Oxidative stress and inflammation are observed in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). As oxidative stress is due to free radicals, free radical scavenging agents, such as vitamin C, are used in the hope of mitigating the severity of COVID‐19. In this paper an analytical model of free radical encounters within a cell is derived. It computes the effectiveness of free radical scavenging and the subsequent reduction in oxidative damage due to therapeutic intervention of exogenous antioxidants. Various publications make claims of success, albeit modest, treating critically ill COVID‐19 patients with high doses of vitamin C. The findings cast doubt on these claims and challenge the notion that any benefits attributed to vitamin C are due to free radical scavenging. [ABSTRACT FROM AUTHOR]

We highlighted in this current paper similar prolonged respiratory presentation with COVID-19 pneumonia in four severely immunocompromised patients currently being treated with anti-CD20 monoclonal antibodies (mAbs), such as ocrelizumab and rituximab, for multiple sclerosis or rheumatoid polyarthritis. Real-time reverse transcription-polymerase chain reaction on a nasopharyngeal swab specimen was negative in all patients. SARS-CoV-2 infection was confirmed from bronchoalveolar lavage fluid. A high titer of post-vaccine COVID-19 convalescent plasma was administered with complete recovery in all patients. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic saw unprecedented resources and funds driven into research for the development, and subsequent rapid distribution, of vaccines, diagnostics and directly acting antivirals (DAAs). DAAs have undeniably prevented progression and life-threatening conditions in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are concerns of antimicrobial resistance (AMR), antiviral resistance specifically, for DAAs. To preserve activity of DAAs for COVID-19 therapy, as well as detect possible mutations conferring resistance, antimicrobial stewardship and surveillance were rapidly implemented in England. This paper expands on the ubiquitous ongoing public health activities carried out in England, including epidemiologic, virologic and genomic surveillance, to support the stewardship of DAAs and assess the deployment, safety, effectiveness and resistance potential of these novel and repurposed therapeutics. [ABSTRACT FROM AUTHOR]

Ozone therapy (OT), a medical procedure, has been showing good results during the coronavirus disease (COVID-19). We aimed to build an evidence and gaps map (EGM) of OT in the COVID-19 ranking the articles found according to levels of evidence and outcomes. The EGM brings bubbles of different sizes and different colors according to the articles. The OT intervention used was major or minor autohemotherapy, rectal insufflation and ozonized saline solution. EGM was based on 13 clinical studies using OT for COVID-19 involving a total of 271 patients. We found 30 outcomes related to OT in COVID-19. Our EGM divided the outcomes into six groups: 1-clinical improvement; 2-hospitalization; 3-inflammatory, thromboembolic, infectious, or metabolic markers; 4-radiological aspects, 5-viral infection and 6-adverse events. Major autohemotherapy was present in 19 outcomes, followed by rectal insufflation. Improvement in clinical symptoms of COVID-19, improvement of respiratory function, improvement of oxygen saturation, reduction in hospital internment, decrease in C-reactive protein, decrease in ferritin, decrease in lactate dehydrogenase, decrease in interleukin 6, decrease in D-dimer, radiological improvement of lung lesions and absence of reported adverse events were related in the papers. The most commonly used concentrations of OT in major autohemotherapy and in rectal insufflation were 40 µg/mL and 35 µg/mL, respectively. Here, we bring the first EGM showing the efficacy and safety of OT in the treatment of COVID-19. OT can be used as integrative medical therapy in COVID-19 at a low cost and improve the health conditions of the patients. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS‐CoV‐2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized patients with venous thromboembolism, particularly those admitted to intensive care units. Moreover, various forms of arterial and venous thrombosis, or micro‐ or macro‐vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in patients with COVID‐19 accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life‐threatening condition. In the current paper, we present a thorough review of the pathophysiology of COVID‐19‐induced hypercoagulable state and the use of anticoagulants to treat SARS‐CoV‐2 infections in different patient groups, as well as their pros and cons. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant recipients show high non-response rates to vaccination despite more than three vaccinations and, consequently, reduced viral clearance capacity when infected while receiving certain immunosuppressants, carrying an elevated risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. SARS-CoV-2 evolution has been characterized by the emergence of novel variants and spike mutations contributing to waning efficacy of neutralizing antibodies. To this end, the therapeutic field expands from vaccination towards a combined approach of immunization, pre-exposure prophylaxis and early post-exposure treatment using direct-acting antivirals and neutralizing monoclonal antibodies to treat early in the disease course and avoid hospitalization. This expert opinion paper from the Immunonephrology Working Group of the European Renal Association (ERA-IWG) summarizes available prophylactic and/or early treatment options (i.e. neutralizing monoclonal antibodies and direct-acting antivirals) of SARS-CoV-2-infected patients with immune-mediated kidney disease, chronic kidney disease and kidney transplant recipients. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has caused significant losses and suffering around the world. Although the SARS-CoV-2 vaccine has largely controlled the spread of the virus, the scientific and sustainable treatment of COVID-19 patients is still necessary to truly end the pandemic. Small-molecule drugs against COVID-19 have attracted the attention of the scientific community and industry owing to their unique advantages such as a simple delivery method, relatively high output, and immune response with lower probability. Fortunately, in the last three years, some potentially effective drugs have been proposed, and have achieved good results in clinical trials. This paper briefly introduces the research progress on small-molecule drugs since 2020 to provide reference for future SARS-CoV-2 research. [ABSTRACT FROM AUTHOR]

Vaccination is an important tool in the fight against the COVID-19 pandemic in patients with haematologic malignancies. The paper provides an analysis of the course of breakthrough SARS-CoV-2 infection in a group of vaccinated patients with haematological malignancy and a comparison with a historical cohort of 96 non-vaccinated patients with haematologic malignancies and bone marrow failure syndromes (two patients) in the treatment of COVID-19. A severe or critical course of COVID-19 was significantly less frequent in the group of vaccinated patients (10.2% vs. 31.4%, p = 0.003). The need for hospitalisation due to COVID-19 was significantly lower in vaccinated patients (27.1% vs. 72.6%, p < 0.0001) and the duration of hospitalisation was significantly shorter (10 vs. 14 days, p = 0.045). Vaccinated patients were insignificantly less likely to require oxygen therapy during infection. COVID-19 mortality was significantly higher in non-vaccinated patients (15.6% vs. 5.1%, p = 0.047). The paper demonstrated a significant positive effect of vaccination against COVID-19 on a less severe clinical course of infection, lower need for hospitalisation and mortality. However, the results need to be evaluated even in the context of new antivirals and monoclonal antibodies against SARS-CoV-2 or virus mutations with different biological behaviour. [ABSTRACT FROM AUTHOR]

Several studies have been directed to find scalable, swift, accurate, and cost‐effective strategies for detecting, monitoring, and treating coronavirus disease 2019 (COVID‐19). Indeed, the lack of a fast and practical method for detecting the infected regions makes decision‐making challenging to combat the critical pandemic‐struck situations. The probable 'wrong', or rather inadequate, decisions not only have a boomerang effect on the economy but also can lead to an increase in the number of infected individuals, degree of hospitalization, and death counts. Although the current clinical methods are effective, they are costly, time‐consuming, and, more particularly, inadequate because of the virus's mutation patterns. In addition, contamination of biomedical wastes with the COVID‐19 virus is a matter of grave concern. Therefore, there is a perpetual need for novel methodologies to delineate the contaminated regions and determine whether those viruses contaminate the wastewater. Although several review papers have been recently published to discuss those concerns, there is a lack of a comprehensive survey of the detection and treatment of the COVID‐19 virus in aqueous media. Herein, we review techniques available as spreading signifiers for detecting the COVID‐19 virus in water resources and wastewater. We classify and integrate techniques into wastewater, sewage, and sludge detection and monitoring. Treatment of COVID‐19‐contaminated wastewater is discussed by classifying and ranking the methodologies nurtured from nanotechnology, including nanoparticle‐based biosensors used in the detection and nanotechnology‐based filtration systems for the removal of COVID‐19 from wastewater. We also highlight the compilation of the detection methodologies in contaminated aqueous media and provide insight into the challenges associated with treating COVID‐19‐contaminated wastewater. The article concludes that international and robust guidelines for virus/bacteria treatment in wastewater are urgently needed to protect the environment and public health, where nanotechnology plays a key role. [ABSTRACT FROM AUTHOR]

Objective: Ephedra herbs are the only extant genus in its family, Ephedraceae, and order, Ephedrales. It has been prescribed in traditional medicine for improving headaches and respiratory infections. On the other hand, because the coronavirus disease 2019 (COVID-19) causes respiratory problems and COVID-19 pandemic is the most widespread outbreak that has affected humanity in the last century, the current review aims using literature search to investigate the effects of the Ephedra herbs compounds on COVID-19 to supply a reference for its clinical application in the inhibition and remedy of COVID-19. Materials and Methods: This review was performed using articles published in various databases, including Web of Science, PubMed, Scopus, and Google Scholar, without a time limit. For this paper, the following keywords were used: "Ephedra", "coronavirus disease 2019", "COVID-19", "Severe acute respiratory syndrome coronavirus 2" or "SARS CoV 2". Results: The results of this review show that the Ephedra herbs have effectiveness on COVID-19 and its compounds can bind to angiotensin-converting enzyme 2 (ACE2) with a high affinity and act as a blocker and prevent the binding of the virus. Conclusion: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19. [ABSTRACT FROM AUTHOR]

BACKGROUND: The pandemic caused by the novel coronavirus disease (COVID-19) since early 2020 is one of the most significant global health issues in history. Although there is currently no specific treatment for COVID-19, researchers have provided a whole array of potential treatments, both from the Western medicine approach, which is molecular target and pathogenesis based, and from the traditional Chinese medicine (TCM) approach, which is based on the exposure to toxins/pathogens and the balance of the body to combat them for recovery. OBJECTIVE: The aim of this research is to find combinations of Western medicine and TCM that may offer better therapeutic efficacy synergystically with a better adverse events profile. The findings of the research may provide a new insight in the development of the treatment of COVID-19. METHODS: From the Western medicine perspective, drugs target the mechanisms of viral infection, including the stages of viral entry (Arbidol, Camostat Mesylate, Convalescent Plasma therapy) and viral replication (Lopinavir/Ritonavir, Redemsivir, Ribavirin). Additional therapies target host defenses, preventing cytokine storms (Tocilizumab) and stimulating the immune system (Interferons). On the other hand, TCM also proposed a number of treatment methods for COVID-19 with new scientific approaches identifying their antiviral and immunomodulatory activities. The novel combination of Western medicine and TCM can be proposed by analyzing their respective molecular targets. RESULTS: Although TCM is not generally accepted in the Western community because of the general lack of knowledge on their detailed mechanisms, studies and clinical trials suggest that TCM could be beneficial in combating COVID-19. CONCLUSION: Based on the principle of combining TCM and Western medicine, two combinations are tested effective in clinical trials, and three possible combinations that might be effective are proposed in the paper. [ABSTRACT FROM AUTHOR]

Background: Patients with coronavirus disease 2019 (COVID-19) undergoing maintenance hemodialysis have a poor prognosis and limited treatment options. Methods: This paper outlines the impact of COVID-19, its treatment, and the efficacy of vaccines in Japanese patients undergoing hemodialysis with a review of the literature. Results: Patients undergoing dialysis in dialysis facilities are at greater risk of exposure to severe acute respiratory syndrome coronavirus 2 than the general population due to limited isolation capabilities. Therefore, vaccines are expected to be effective for patients undergoing dialysis. In addition, effective use of available medications is important because treatment options are limited. Conclusions: Efforts should be made to prevent the spread of the infection to high-risk patients undergoing dialysis while ensuring the effective use of vaccines. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) announced the Coronavirus disease (COVID-19), which is triggered by SARS-CoV-2 virus, on March 11, 2020. Nations all over the world reacted quickly, enacting various mitigation measures such as travel and movement restrictions, prohibitions on meeting, generalized or partial lockdowns, handwashing, and promotion of good hygiene and health. Corona virus outbreaks have claimed the lives of many people globally since 2019, with an estimated of over 5 million people infected. The world health organization since the announcement of the COVID-19 pandemic released statements about nations working towards finding a vaccine for the virus. Furthermore, with 80% of African population depending on traditional medicine, a spotlight was on the WHO about their views on African traditional medicine, which is a component of African indigenous Knowledge Systems as one of the COVID-19 treatments. The WHO therefore declared that traditional medicine would undergo clinical trials to check its potential as COVID-19 treatment. The paper examines the effects of COVID-19 in Africa, as well as existing clinical trials in African traditional medicine to cure and treat the virus, using existing literature. In addition, the paper considers the future of traditional medicine in the pharmaceutical and other medical plant industries. [ABSTRACT FROM AUTHOR]

Remdesivir (RDV) is the only antiviral drug approved for COVID-19 therapy by the FDA. Another drug LAGEVRIO™ (molnupiravir) though has not been approved yet by FDA but has been authorized on December 23, 2021, for emergency use to treat adults with mild-to moderate COVID-19 symptoms and for whom alternative COVID-19 treatment options are not clinically appropriate. The fact is that the efficacy of RDV is, however, limited in vivo though it is highly promising in vitro against SARS-CoV-2 virus. In this paper we are focusing on the action mechanism of RDV and how it can be improved in vivo. The stability of RDV alone and on encapsulation with our platform technology based polymer NV-387 (NV-CoV-2), were compared in presence of plasma in vitro and in vivo. Furthermore, a non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV CoV-2 (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats was done. In addition, the antiviral activity of NV-CoV-2 and NV-CoV-2-R was compared with RDV in a cell culture study. The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma-mediated catabolism in both in vitro and in vivo, studies; (ii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2 and NV-CoV-2-R) showed no toxic effects. (iii) Body weight measurements and survival rates of the NL-63 infected rats were similar to the uninfected rats after treatment with NV-CoV-2 and NV-CoV-2-R. Overall, the efficacy as an antiviral regimens were found in this order as below; NV-CoV-2-R > NV-CoV-2 > RDV. Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect against different variants of the coronaviruses. First, NV-CoV-2 is an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit. All together, NV-CoV-2-R is the safest and efficient regimen against COVID-19. [ABSTRACT FROM AUTHOR]

With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient's characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic is known to affect several body organs, including the liver. This results from several factors such as direct effect of SARS-CoV-2 on the liver, side effects of drug therapy and pre-existing liver diseases. Drug-induced liver injury can result from a range of drugs used in the treatment of COVID-19 such as antiviral drugs, anti-inflammatory drugs, antibiotics, herbal medications and vaccines. Metabolism of most drugs occurs in the liver, and this leaves the liver at risk of medication-induced liver damage. Being among pathologies from the disease, COVID-19 liver injury presents with abnormally high liver-related enzymes, such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphate (ALP), and gamma-glutamyl transferase. It is reversible, generally not severe and occurs more mildly in children. However, COVID-19-associated liver injury is worsened by chronic liver diseases and vice versa. There is a high risk of abnormal ALT and AST, in-hospital liver injury and prolonged SARS-CoV-2 shedding in COVID-19 patients with previously existing metabolic-associated fatty liver disease. COVID-19-associated liver injury also appears to be severe and significantly associated with life-threatening COVID-19 and mortality in persons with a history of liver transplant. Where necessary, only supportive management is usually indicated. This paper evaluates the aetiology, clinical and laboratory features, occurrence and management of COVID-19-associated liver injury. It also elaborated on the role of drug therapy in the development of COVID-19 liver injury. [ABSTRACT FROM AUTHOR]

The corona virus disease 2019 (COVID-19) pandemic, which originated in the city of Wuhan, China, has rapidly spread to various countries, with many cases having been reported. Some existing antiviral agents showed positive results to inhibit the infection and transmission of the novel corona virus 2019 (2019-nCoV) in vitro. Covaxin is India's first indigenous COVID-19 vaccine. In this paper, we introduce the Gourava and hyper-Gourava polynomials of a graph. We compute the Gourava and hyper-Gourava polynomials of some specific class of graphs. Further, we obtain the Gourava and hyper-Gourava polynomials of some chemical structures viz., chloroquine, hydroxychloroquine, remdesivir and theaflavin which were used in the treatment of COVID-19. The Gourava and hyper-Gourava indices are investigated for the aforesaid antiviral drugs using polynomial approach. The Indian Council of Medical Research and Bharat Biotech announced that Phase 3 results of covaxin, developed by them, have shown an interim vaccine efficacy of 81 percent. So, the results obtained may be useful for finding the design of new medicine for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

The sudden outbreak of the novel coronavirus pandemic in 2019 disrupted the normal order of life and work, and the virus is still a major threat prevailing the globe. Confronted with the unknown virus, citizens have been following government policies of COVID-19 treatment and containment, and actively improving their immunity through physical activity (PA). This paper is concerned with ways to guide or promote people's willingness to exercise, one of the most effective means to boost immunity. Based on the "attitude–intention" correlation defined in the theory of planned behaviour (TPB), this study, by synchronizing online data about workouts, explores the influence of people's attitudes towards PA behaviour in promoting their intentions to engage in such behaviours as a means to fight the pandemic. In addition, the attitudes towards the use of sports apps and the epidemic are also reckoned with to investigate influencing factors promoting physical activity during the lockdown. The results of the study have been derived from the data of 1223 valid questionnaires, which are subjected to hierarchical regression analysis. Attitudes towards exercise and the use of sports apps are proven to have a significant impact on PA intentions, and the two variables are in direct proportion, with more positive attitudes leading to higher intentions; in contrast, attitudes towards the epidemic do not exhibit an obvious effect. In this light, it is advisable that when clinicians treat COVID-19 patients and medical departments respond to the epidemic, they actively make affirmative influences on peoples' attitudes towards exercise and formulate appropriate exercise plans based on indicators detected and recorded by sports apps such as vital capacity, heart rate, respiratory index and self-perceived intensity to help them face the risk of the epidemic with more confidence. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an unprecedented threat to public health. The pandemic has been sweeping the globe, impacting more than 200 countries, with more outbreaks still lurking on the horizon. At the time of the writing, no approved drugs or vaccines are available to treat COVID-19 patients, prompting an urgent need to decipher mechanisms underlying the pathogenesis and develop curative treatments. To fight COVID-19, researchers around the world have provided specific tools and molecular information for SARS-CoV-2. These pieces of information can be integrated to aid computational investigations and facilitate clinical research. This paper reviews current knowledge, the current status of drug development and various resources for key steps toward effective treatment of COVID-19, including the phylogenetic characteristics, genomic conservation and interaction data. The final goal of this paper is to provide information that may be utilized in bioinformatics approaches and aid target prioritization and drug repurposing. Several SARS-CoV-2-related tools/databases were reviewed, and a web-portal named OverCOVID (http://bis.zju.edu.cn/overcovid/) is constructed to provide a detailed interpretation of SARS-CoV-2 basics and share a collection of resources that may contribute to therapeutic advances. These information could improve researchers' understanding of SARS-CoV-2 and help to accelerate the development of new antiviral treatments. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a pandemic whose adverse effects have been felt all over the world. As of August 2022, reports indicated that over 500 million people in the world had been infected and the number of rising deaths from the disease were slightly above 6.4 million. New variants of the causative agent, SARS-CoV-2 are emanating now and then and some are more efficacious and harder to manage. SARSCoV-2 main protease (Mpro) has essential functions in viral gene expression and replication through proteolytic cleavage of polyproteins. Search for SARS-CoV-2 Mpro inhibitors is a vital step in the treatment and management of COVID-19. In this study, we investigated whether alkaloids with antiviral and myriad other bioactivities from the genus Lycoris can act as SARS-CoV-2 Mpro inhibitors. We conducted a computer-aided drug design study through screening optimal ligands for SARS-CoV-2 Mpro from a list of over 150 Lycoris alkaloids created from online databases such as ChEMBL, PubChem, ChemSpider, and published journal papers. The In silico study involved molecular docking of Lycoris alkaloids to SARS-CoV-2 Mpro active site, absorption, distribution, metabolism, elimination and toxicity (ADMET) screening and finally molecular dynamic (MD) simulations of the most promising ligand-SARS-CoV-2 Mpro complexes. The study identified 3,11-dimethoxy-lycoramine, narwedine, O-demethyllycoramine and epilycoramine as drug-like and lead-like Lycoris alkaloids with favorable ADMET properties and are very likely to have an inhibition activity on SARSCoV-2 Mpro and may become potential drug candidates. [ABSTRACT FROM AUTHOR]

Background: A global pandemic has been declared for coronavirus disease 2019 (COVID-19), which has serious impacts on human health and healthcare systems in the affected areas, including Vietnam. None of the previous studies have a framework to provide summary statistics of the virus variants and assess the severity associated with virus proteins and host cells in COVID-19 patients in Vietnam.Method: In this paper, we comprehensively investigated SARS-CoV-2 variants and immune responses in COVID-19 patients. We provided summary statistics of target sequences of SARS-CoV-2 in Vietnam and other countries for data scientists to use in downstream analysis for therapeutic targets. For host cells, we proposed a predictive model of the severity of COVID-19 based on public datasets of hospitalization status in Vietnam, incorporating a polygenic risk score. This score uses immunogenic SNP biomarkers as indicators of COVID-19 severity.Result: We identified that the Delta variant of SARS-CoV-2 is most prevalent in southern areas of Vietnam and it is different from other areas in the world using various data sources. Our predictive models of COVID-19 severity had high accuracy (Random Forest AUC = 0.81, Elastic Net AUC = 0.7, and SVM AUC = 0.69) and showed that the use of polygenic risk scores increased the models' predictive capabilities.Conclusion: We provided a comprehensive analysis for COVID-19 severity in Vietnam. This investigation is not only helpful for COVID-19 treatment in therapeutic target studies, but also could influence further research on the disease progression and personalized clinical outcomes. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic poses an ongoing global challenge, and several risk factors make people with multiple sclerosis (pwMS) particularly susceptible to running a severe disease course. Although the literature does report numerous articles on the risk factors for severe COVID-19 and vaccination response in pwMS, there is a scarcity of reviews integrating both these aspects into strategies aimed at minimizing risks. The aim of this review is to describe the risk of vulnerable pwMS exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues related to the SARS-CoV-2 vaccine and to evidence possible future strategies in the clinical management of pwMS. The authors searched for papers on severe COVID-19 risk factors, SARS-CoV-2 vaccination and people with multiple sclerosis in support of this narrative literature review. We propose a multilevel strategy aimed at: the evaluation of risk factors for severe COVID-19 in people with multiple sclerosis, identifying the most appropriate vaccination schedule that is safe for people on disease-modifying drugs (DMDs) and a strict follow-up of high-risk people with multiple sclerosis to allow for the prompt administration of monoclonal antibodies to manage COVID-19 risks in this patient population. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 19 (COVID-19), a disease that has affected more than 500 million people worldwide since the end of 2019. Due to its high complications and death rates, there is still a need to find the best therapy for SARS-CoV-2 infection. The dysregulation of the inflammatory response in COVID-19 plays a very important role in disease progression. It has been observed that abnormal activity of Nuclear Factor kappa B (NF-κB) is directly associated with, inter alia, increased synthesis of proinflammatory factors. Therefore, this review paper focuses on the functions of NF-κB in the development of SARS-CoV-2 infection and potential application of NF-κB inhibitors in COVID-19 immunotherapy. A comprehensive literature search was performed using the MEDLINE/PubMed database. In the current review, it is highlighted that NF-κB plays important functions in the modulation of an adaptive inflammatory response, including inducing the expression of proinflammatory genes. Increased activation of NF-κB in SARS-CoV-2 infection was observed. The association between NF-κB activation and the expression of SARS-CoV-2 structural and non-structural proteins were also reported. It was observed that modulation of NF-κB using, e.g., traditional Chinese medicine or glucocorticosteroids resulted in decreased synthesis of proinflammatory factors caused by SARS-CoV-2 infection. This review summarizes the role of NF-κB in COVID-19 and describes its potential immunotherapeutic target in treatment of SARS-CoV-2 infection. However, indisputably more studies involving patients with a severe course of COVID-19 are sorely needed. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS‐CoV‐2 lifecycle and COVID‐19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID‐19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as "pivotal clinical trials" (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) is a newly discovered infectious coronavirus, which can cause Coronavirus Disease 2019 (COVID-19). The outbreak of the disease has caused severe impact both at home and abroad. Compared with the other three structural proteins encoded by SARS-CoV-2, Nucleocapsid phosphoprotein (Np) is more conservative and plays an important role in pathogen diagnosis, vaccine design, and treatment. This paper aims to predict the spatial structure of Np in Wuhan-Hu-1 strain and its B-cell epitope,and lay a foundation for the development of epitope vaccine and related monoclonal antibody of SARS-CoV-2. In this study, the Neighbor-joining method in MEGA5.05 was used to construct a phylogenetic tree based on the base sequence of Np of SARS-CoV-2 strain. The SARS-CoV-2 Wuhan-Hu-1 strain was used as the research object, and parameters such as hydrophilicity index, flexible region, surface possibility, and antigenic index were analyzed and predicted by the Protean module in the DNAStar software, combined with the spatial structure simulated by the Phyre2 online tool, so as to comprehensively predict the dominant B-cell epitopes of Np of Wuhan-Hu-1. Results show that the gene sequences of Np of SARS-CoV-2 isolated from different regions were highly similar (99.6%-100%). The amino acid sequence of Np in Wuhan-Hu-1 strain was 419 aa.The spatial structure of Np in Wuhan-Hu-1 strain was fairly regular. It contained only a small amount of α-helixes, while most of the structures were β-sheets, β-turns, and random coils. Results of multi-parameter comprehensive analysis showed that the possible antigenic epitope regions of B-cell were located in the amino acid regions of 52-9,9-5,3-9,6-5,9-4,0-6,4-6,7-7,3-9,7-3,9-5,3-9,7-3,9-5,9-401,and 403-411. The results of this study can provide theoretical information for the development of epitope vaccine, rapid diagnostic reagents, and monoclonal antibodies with respect to SARS-CoV-2, and offer new strategies for COVID-19 treatments. [ABSTRACT FROM AUTHOR]

COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2, which rapidly spreads via respiratory droplets and is the cause of the current pandemic. In this alarming situation, it is a delicate matter how to visit patients safely and how to manage their chronic treatments. The aim of this paper is to examine in detail the potential impact on SARS-CoV-2 infection of treatments routinely used in trichology and to provide a useful guide for the therapeutic management of trichological patients in this new COVID-19 era. [ABSTRACT FROM AUTHOR]

We have previously published several papers illustrating numerous immunomodulatory and anti-inflammatory potential benefits when we repurposed safe, generic non-steroidal anti-inflammatory drugs (NSAIDs)/nitazoxanide/azithromycin (Kelleni's protocol), to early manage our COVID-19 pediatric, adult, and pregnant patients. In this manuscript, we discuss some recently published meta-analysis and clinical studies supporting our practice and discuss a molecular study that might be interpreted as an academic proof that our protocol might also prevent SARS-CoV-2 replication. Moreover, after aspirin has been suggested to be independently associated with reduced risk of mechanical ventilation, ICU admission and in-hospital mortality of COVID-19, we claim that the molecular interpretation of the results that led to this suggestion was not scientifically accurate, and we provide our academic interpretation confirming that low-dose aspirin is least likely to improve COVID-19 mortality through anticoagulation as was suggested. Furthermore, we describe other potential benefits related to aspirin-triggered lipoxins and resolvins while illustrating how NSAIDs interfere with COX-1, COX-2, SARS-CoV-2/ SARS-CoV-2 ORF protein-dependent activation of caspases and their subsequent mitochondrial dysfunction, endoplasmic reticulum stress, apoptosis and necroptosis which were associated with COVID-19 complications. Similarly, NSAIDs are known caspase inhibitors and thus they might independently inhibit other caspase-related COVID-19-associated downstream pathological signaling mechanisms. Finally, we postulated that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in the development of severe and critical COVID-19 and confirmed our old call to early adopt NSAIDs, as an integral part of Kelleni's protocol, as of choice in its management aiming to end this pandemic. [ABSTRACT FROM AUTHOR]

New coronavirus disease 2019 (COVID‐19), as a pandemic disaster, has drawn the attention of researchers in various fields to discover suitable therapeutic approaches for the management of COVID‐19 patients. Currently, there are many worries about the rapid spread of COVID‐19; there is no approved treatment for this infectious disease, despite many efforts to develop therapeutic procedures for COVID‐19. Emerging evidence shows that mesenchymal stromal/stem cell (MSC) therapy can be a suitable option for the management of COVID‐19. These cells have many biological features (including the potential of differentiation, high safety and effectiveness, secretion of trophic factors and immunoregulatory features) that make them suitable for the treatment of various diseases. However, some studies have questioned the positive role of MSC therapy in the treatment of COVID‐19. Accordingly, in this paper, we will focus on the therapeutic impacts of MSCs and their critical role in cytokine storm of COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has affected the world extraordinarily. This disease has a potential to cause a significantly severe course of disease leading to respiratory complications, multiple organ failure and possibly death. In the fight against this pandemic-causing disease, medical professionals around the world are searching for pharmacological agents that could treat and prevent disease progression and mortality. To speed the search of promising treatment options, already existing pharmacological agents are repurposed for the potential treatment of COVID-19 and tested in clinical trials. The aim of this literature review is to investigate the efficacy and safety of repurposed pharmacological agents for the treatment of COVID-19 at different pathophysiologic stages of the disease. For this literature review, online-databases PubMed and Google Scholar were utilised. Keywords "COVID-19", "SARS-CoV-2", "pathogenesis", "drug targets", "pharmacological treatment", "cytokine storm", "coagulopathy" and individual drug names were used. Scientific articles, including reviews, clinical trials, and observational cohorts, were collected and analysed. Furthermore, these articles were examined for references to find more clinical trials testing for the potential treatment of COVID-19. In total, 97 references were used to conduct this research paper.Results: The most beneficial pharmacological agent for the treatment of COVID-19 are corticosteroids, especially dexamethasone, for the treatment of mechanically ventilated COVID-19 patients. Other promising agents are remdesivir for the treatment of patients with COVID-19 pneumonia requiring minimal supplemental oxygen therapy, and IL-6 receptor antagonist monoclonal antibodies in severe COVID-19. Lopinavir/ritonavir, as well as chloroquine or hydroxychloroquine with or without azithromycin demonstrate the least efficacy in the treatment of COVID-19. The clinical benefits of the treatment of a COVID-19-specific coagulopathy with increased dosing of anticoagulation need further research and confirmation of randomised controlled trials.Conclusion: The search for pharmacological treatment of COVID-19 has elicited great controversy. Whereas drugs like chloroquine, hydroxychloroquine, and lopinavir/ritonavir have not shown proven benefit, the agents remdesivir and dexamethasone are recommended for clinical use for the treatment of COVID-19. Further randomised trials for other pharmacological treatment strategies are awaited. [ABSTRACT FROM AUTHOR]

This paper aims to discuss how blood coagulation causes thromboembolic manifestations, including deep vein thrombosis (DVT), pulmonary embolism (PE), and other venous thrombosis events (VTE) and the possible mechanism and the effectiveness of using anticoagulant drugs in severely ill COVID-19 patients. This review is based on literature search through electronic databases of PubMed, UpToDate, Medline, Embase, International Pharmaceutical Abstract (IPA) and clinicaltrials.gov from December 2019 (since covid-19 emergence) to end of 2020. This review used keywords combination related to the association between covid-19 and blood coagulation (DVT, PE and other VTE), as well as clinical trials of anticoagulant drugs for the treatment of covid-19 patients. We summarized that thromboembolism incidence in severely symptomatic (ICU) patients ranges from 16.7 to 85 %. Furthermore, the main D-Dimer parameter had a significant difference between VTE (non-survival) and non-VTE (survival) patients. Meanwhile, the possible mechanism is the increased levels of complement and cascade components, including C1R, C1QC, C3b/C4b receptor 1 (CR1), C3, coagulation factors II, V, IX, and X, as well as reactive antiphospholipid antibodies affecting hypercoagulability, platelet activation, aggregation, and adhesion. Studies have shown the existence of thrombosis events in severe COVID-19 patients as well as the effectiveness of anticoagulants therapy in early prognosis, but the results of phase 3 clinical trials are still under investigation at several centers. [ABSTRACT FROM AUTHOR]

Objective: Treatment for COVID-19 is still urgent need for the critically ill and severe cases. UC-MSC administration has a therapeutic benefit for severe COVID-19 patients even in the recovery period. In this paper, we aimed to present our clinical experience with UC-MSC treatment in severe and critical severe COVID-19 patients. Methods: In this study we evaluated the clinical outcome of severe/critically severe 210 COVID-19 patients treated with UC-MSCs, 1–2 × 106 per kilogram to 210 patients from 15/10/2020 until 25/04/2021. Results: Out of 99 critically severe intubated patients we have observed good clinical progress/discharged from ICU in 52 (52.5%) patients. Where as 86 (77.5%) of 111 severe unintubated patients discharged from ICU. Intubated 47 (47.5%) patients and unintubated 25 (22.5%) patients pass away. Significantly higher survival was observed in patients who underwent UC-MSCs before intubation (OR = 1.475, 95% CI = 1.193–1.824 p < 0.001). It was observed that the SaO2 parameter tended to improve after UC-MSC therapy compared to all groups. But SaO2 parameter between intubated and unintubated groups was not statistically significant (p > 0.05), while in discharged cases SaO2 parameter was statistically significant (p = 0.01). Besides, there was a statistically significant relation with intubation status, age (OR = 3.868, 95% CI = 0.574–7.152 p = 0.02) and weigh (OR = 6.768, 95% CI = 3.423–10.112 p < 0.001) thus presented an elevated risk for COVID-19. The linear regression analysis confirmed that the high weight was associated with the risk of intubation in COVID-19 (p = 0.001). Conclusions: According to our results and from recent studies, UC-MSC treatment is safe with high potential to be used as an added therapeutic treatment for severe COVID-19 patients. Our experience showed that UC-MSC therapy may restore oxygenation and downregulate cytokine storm in patients hospitalized with severe COVID-19. We advice wider randomised studies to discover the detailed therapeutic pathophysiology of the MSCs on COVID-19 patients. MSCs transplantation improves the damaging effects of the cytokine storm through immunomodulation and improving tissue and organ repair. Severe patients who were unintubated were in the Phase I, while critical patients who were intubated were in the Phase II. The figure is created via biorender application, (BioRender.com). [ABSTRACT FROM AUTHOR]

Coronavirus disease 19 (COVID-19) continues to rage as a global pandemic. A number of potential therapeutic agents have been explored over the past year or two. However, numerous drugs that were expected to prove highly effective, such as lopinavir/ritonavir and remdesivir, have been found to have little benefit in large clinical trials. Interleukin-6 receptor antagonists, glucocorticoids, Janus kinase inhibitors, and some antivirals have been found to provide significant benefits in terms of reducing viral load, reducing the time of nucleic acid conversion, or improving survival. For example, bamlanivimab and etesevimab, which are newly designed monoclonal antibodies against the surface spike protein S1 subunit receptor-binding domain (RBD) of SARS-CoV-2, have a significant effect on reducing the viral load and the hospitalization rate of patients with mild COVID-19. Several vaccines against SARS-CoV-2 have been widely administered worldwide and have provided good protection. Nevertheless, the increasingly hardy variants of the virus have raised the requirements for vaccine design. Perhaps RBD-based vaccines are a viable way to defend against variants, but this still needs to be verified in a large sample. Therefore, this paper provides an update on the treatment options for COVID-19 based on three previously proposed dimensions of drug screening: standard assays of existing broad-spectrum antivirals, screening of chemical libraries, and redevelopment of new, specific drugs. [ABSTRACT FROM AUTHOR]

Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies. [ABSTRACT FROM AUTHOR]

Convalescent plasma therapy (CP) has long been used to prevent and treat various infectious diseases before COVID-19 such as SARS, MERS, and H1N1. Because the viral and clinical characteristics of COVID-19 share the similarities between SARS and MERS, CP treatment could be a promising treatment option to save COVID-19. With only low quality medical evidence, but massive media support and a very significant public demand for the use of convalescent plasma for COVID-19, we are now faced with an ethical dilemma. Therefore, this paper uses a structured analysis that focuses on the preferred reporting items for a systematic review of ethical issues regarding the use of Convalescent Plasma Therapy for COVID-19. The use of convalescent plasma must meet the ethical principles of autonomy; such as voluntary, informed consent, and confidentiality. Consideration of the risk-benefit ratio for potential donor recipients also needs to be considered in order to meet the beneficence and non-maleficence principles. The principle of justice also needs to be applied both to donors, donor recipients and health workers, such as determining the priority of donor recipients, due to the increasing demand for convalescent plasma amid the limited circumstances of patients who have recovered from Covid-19 who voluntarily donate. [ABSTRACT FROM AUTHOR]

Background: The global scientific community has been quick to respond to health crisis unleashed by Covid-19 pandemic with intensified investments in R&D and thereby it gave new impetus to Covid-19 research. The world has come to witness unprecedented increase in research publications on control and treatment of Covid-19 pandemic. Like any other region in the world, South Asia too has been the worst-hit region and it too witnessed increase in Covid-related research studies. Systematic reviews of such literature and bibliometric studies are used nowadays as tools to identify and analyze key and significant South Asian contribution to the subject. The present study aims to assess and quantify the contribution and impact of Covid-19 research made by a group of select four South Asian countries. Methods: Publications data on Covid 19 covering the period between December 2019 and 8.7.2021 was sourced from the Scopus database. VOSviewer 1.6.14 software was applied to generate network maps, assess hot topics in the area and describe collaboration patterns in research between different countries. Results: A total of 18,64,275 publications reflecting the global research output on Covid-19 were retrieved from the Scopus database. The publications data of select four South Asian countries - Pakistan, Bangladesh, Nepal and Sri Lanka - was also retrieved. Comparatively the data size of select four South Asian countries was small, limited to 4012 documents, and accounting for a 2.15% share of the global research output on Covid-19 virus. Pakistan published the most number of Covid-19 publications (n = 2246, 55.58%), followed by Bangladesh (n = 1203, 29.99%), Nepal (n=512, 12.76%) and Sri Lanka (n=202, 5.03%). The United States as the collaborating partner in most number of publications contributed by South Asian countries (n = 609, 25.41%), followed by the United Kingdom (n = 496, 20.69%), China (n=453, 18.90%), Saudi Arabia (n=441, 18.40%) and India (n=426, 17.77%). Covid-19 treatment type was the most studied topic in the contributions made by South Asian countries accounting for a 16.45% share, followed by epidemiology (15.63%), risk factors (5.835), clinical studies (4.81%), etc. Conclusion: This paper finds that the quantity and quality of research pursued by a select group of four South Asian countries in the domain of Covid 19 studies has so far been small and insignificant. There is an urgent need on the part of select group of South Asian counties to improve their productivity and qualitative performance at the national, institutional, and individual author level. [ABSTRACT FROM AUTHOR]

Background/aim: The aim of this descriptive article is to share the experience in Ege University, Turkey with favipiravir in the treatment of severe SARS-CoV-2 pneumonia. Materials and methods: This retrospective descriptive study included patients diagnosed with COVID-19 who presented with or developed severe pneumonia. Results: Forty patients who completed a full course (at least 5 days) of favipiravir were included in the study. At baseline, 30 (75%) patients required treatment for respiratory distress. Thirty-three patients (82.5%) were discharged from the hospital with full recovery, 6 patients (15%) died and 1 case (2.5%) was still at the intensive care unit (ICU) when this paper was written. Conclusion: This study provides relevant information for the treatment of COVID-19, suggesting that favipiravir was associated with significant clinical and laboratory improvements in the majority of the patients, is a safe drug with no serious side effects and would merit further investigation. [ABSTRACT FROM AUTHOR]

Due to the high prevalence and long incubation periods often without symptoms, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected millions of individuals globally, causing the coronavirus disease 2019 (COVID-19) pandemic. Even with the recent approval of the anti-viral drug, remdesivir, and Emergency Use Authorization of monoclonal antibodies against S protein, bamlanivimab and casirimab/imdevimab, efficient and safe COVID-19 vaccines are still desperately demanded not only to prevent its spread but also to restore social and economic activities via generating mass immunization. Recent Emergency Use Authorization of Pfizer and BioNTech's mRNA vaccine may provide a pathway forward, but monitoring of long-term immunity is still required, and diverse candidates are still under development. As the knowledge of SARS-CoV-2 pathogenesis and interactions with the immune system continues to evolve, a variety of drug candidates are under investigation and in clinical trials. Potential vaccines and therapeutics against COVID-19 include repurposed drugs, monoclonal antibodies, antiviral and antigenic proteins, peptides, and genetically engineered viruses. This paper reviews the virology and immunology of SARS-CoV-2, alternative therapies for COVID-19 to vaccination, principles and design considerations in COVID-19 vaccine development, and the promises and roles of vaccine carriers in addressing the unique immunopathological challenges presented by the disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Novel coronavirus disease (COVID-19) has attracted much attention around the world due to its rapid transmission among humans and relatively high mortality rate. Studies are increasing to find the best therapeutic approach for the disease and its management. Regenerative medicine offers various cell-tissue therapeutics and related products, such as stem cell therapy, natural killer (NK) cell therapy, Chimeric antigen receptor (CAR) T cell therapy, exosomes, and tissue products. Interestingly, mesenchymal stem cells (MSCs) can reduce inflammatory symptoms and protect against cytokine storm, which critically contributes to the COVID-19 progression. Notably, having the potentials to exert cytotoxic effects on infected cells and induce interferon production probably make NK cells a candidate for COVID-19 cell therapy. Besides, exosomes are one of the crucial products of cells that can exert therapeutic effects through the induction of immune responses and neutralizing antibody titers. The paper aims to briefly consider current options for COVID-19 therapy to show that there is no specific cure for COVID-19, and then assess the real opportunities and range of promises regenerative medicine can provide for specific treatment of COVID-19. [ABSTRACT FROM AUTHOR]

The paper presents the results of a standard and complex treatment method using the peptide drug thymus thymalin in patients with COVID-19. One of the mechanisms of the immunomodulatory effect of thymalin is considered to be the ability of this peptide drug to influence the differentiation of human hematopoietic stem cells (HSCs). It was found that, as a result of standard treatment, patients in the control group showed a decrease in the concentration of the pro-inflammatory cytokine IL-6, C-reactive protein, D-dimer. The addition of thymalin to standard therapy accelerated the decline in both these indicators and the indicators of the T cell system. This has helped reduce the risk of blood clots in COVID-19 patients. The revealed properties of the thymus peptide preparation are the rationale for its inclusion in the complex treatment of coronavirus infection. Peptideswith potential biological activity against SARS-CoV-2 virus [29]. Note: Nitrogen atoms are shown in blue, oxygen atoms - in red, carbon atoms – in gray, hydrogen atoms – in white, and phosphorus atoms – in yellow [ABSTRACT FROM AUTHOR]

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving situation. New discoveries about COVID-19 and its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to deepen the understanding of this novel disease. As there is currently no COVID-19 specific treatment, isolation is the most effective method to prevent transmission. Moreover, development of a safe and effective COVID-19 vaccine will be instrumental in reinstating pre-COVID-19 conditions. As of 31 July 2020, there are at least 139 vaccine candidates from around the globe in preclinical evaluation, with another 26 undergoing clinical evaluation. This paper aims to review the basics of COVID-19, including epidemiology, basic biology of SARS-CoV-2, and transmission. We also review COVID-19 vaccine development, including animal models, platforms under development, and vaccine development in Canada. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), the deadly disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a global pandemic that has severely affected lives and economies around the globe. The spread of this virus will be very difficult to contain if no vaccine is ready for implementation. This is because of the high human-to-human trans-mission rate of this virus and the fact that the virus is in the community spread stage. As of 31st August 2020, 25.3 million individuals have been affected by this deadly virus resulting in about 850,673 deaths. To combat the spread of COVID-19, more than 100 applicant immunizations are being developed around the world. Among them, eight have begun or will be soon beginning preliminary clinical trials. This paper provides a review of the current developments of potential COVID-19 vaccines around the world. It specifically discusses the recombinant vaccine produced by the University of Oxford and Astra Zeneca (Cambridge, UK), the use of novel self-amplifying RNA technique to create a vaccine and the progress made by UNAID (US National Institute of Allergy and Infectious Diseases) and World Health Organization (WHO). Further-more, this review demonstrates the pharmaceutical prophylaxis and treatment protocols for COVID-19 by analysing the documentation set up by the WHO for up to date data with respect to the novel coronavirus of 2019–2020. [ABSTRACT FROM AUTHOR]

In this paper, we present a new mathematical model to describe the evolution of the COVID-19 in countries under the state of emergency. Where the COVID-19 pandemic is sweeping country after country. The Italian and Moroccan authorities have declared a state of emergency in response to the growing threat of this novel coronavirus (COVID- 19) outbreak by March 09 and 20, respectively. In-state of emergency, citizens cannot go out to public spaces without special authorization from local authorities. But after all these efforts exerted by these authorities, the number of new cases of the COVID-19 continues to rise significantly, which confirms the lack of commitment of some citizens. First, we aim to investigate the cause of new infections despite all strategies of control followed in these countries including media reports, awareness, and treatment, self-distancing and quarantine, by estimating the number of these people who underestimate the lives and safety of citizens and put them at risk. To do this, we use real data of the COVID-19 in Italy and Morocco to estimate the parameters of the model, and then we predict the number of these populations. Second, we propose an optimal control strategy that could be the optimal and the efficient way for the Moroccan and Italian authorities and other countries to make the state of emergency more efficient and to control the spread of the COVID-19. The model is analyzed for both countries and then to compare the implications of the obtained results. Numerical examples are provided to illustrate the efficiency of the strategy of control that we propose and to show what would have been happened in Morocco and Italy if this strategy of control was applied early. [ABSTRACT FROM AUTHOR]

Despite COVID-19 turned into a pandemic, no approved drug for the treatment or globally available vaccine is out yet. In such a global emergency, drug repurposing approach that bypasses a costly and long-time demanding drug discovery process is an effective way in search of finding drugs for the COVID-19 treatment. Recent studies showed that SARS-CoV-2 uses neuropilin-1 (NRP1) for host entry. Here we took advantage of structural information of the NRP1 in complex with C-terminal of spike (S) protein of SARSCoV-2 to identify drugs that may inhibit NRP1 and S protein interaction. U.S. Food and Drug Administration (FDA) approved drugs were screened using docking simulations. Among top drugs, well-tolerated drugs were selected for further analysis. Molecular dynamics (MD) simulations of drugs-NRP1 complexes were run for 100 ns to assess the persistency of binding. MM/GBSA calculations from MD simulations showed that eltrombopag, glimepiride, sitagliptin, dutasteride, and ergotamine stably and strongly bind to NRP1. In silico Alanine scanning analysis revealed that Tyr297, Trp301, and Tyr353 amino acids of NRP1 are critical for drug binding. Validating the effect of drugs analyzed in this paper by experimental studies and clinical trials will expedite the drug discovery process for COVID-19. [ABSTRACT FROM AUTHOR]

Implication for health policy/practice/research/medical education: Autophagy is a way to create new cellular structures, clear cells invaded by microbes, and block accumulating proteins that can cause disease. Moreover, it can destroy all cellular organs and pathogens, including fungi, parasites, bacteria, and viruses, either randomly or selectively. Many research groups are examining a strategy to combat COVID-19. In particular, research is underway to identify drugs that can target autophagy in COVID-19 virus infection. Several known drugs are currently under clinical evaluation for the autophagy process, given that regulating autophagy is a way to combat COVID-19. This study introduces drugs that target the autophagy pathway. Please cite this paper as: Aleebrahim-Dehkordi E, Saberianpour S, Soleiman-Dehkordi E, Hooshyar D, Mojtahedi Z, Kianpour N, Hasanpour-Dehkordi A, Saberian L, Akhavan Sepahi M. Autophagy and treatment of patients with COVID-19; which drugs target the autophagy pathway? J Nephropathol. [ABSTRACT FROM AUTHOR]

The ongoing coronavirus disease 2019 (COVID-19) outbreak was declared a pandemic by the World Health organization in early March 2020. The disease typically presents with viral respiratory symptoms that could progress to acute respiratory distress syndrome. Emerging evidence suggests different possible dermatologic manifestations of COVID-19, including: acral lesions (pernio-like, pseudo-chillblain), vesicular eruptions, macular and papular exanthema, urticaria, livedoid, purpuric and petechial rashes. However, specific skin manifestations of the COVID-19 disease have not yet been clearly established and the relationship between the appearance of skin lesions and SARS-CoV-2 infection is still unclear. These highly variable skin changes could represent a direct consequence of the viral infection, an immunological response to viral nucleotides, adverse reactions to drugs frequently used for the treatment of COVID-19, or other disorders. In a global effort to comprehend the exact cutaneous features of COVID-19, several international dermatological societies have initiated nationwide studies to analyze COVID-19 cutaneous manifestations during this pandemic. This paper represents a literature review of the scientific data available on the clinical characteristics and symptoms of the cutaneous manifestations associated with COVID-19. Such findings are extremely useful in establishing if dermatological manifestations in COVID-19 patients could harbor a diagnostic significance and subsequently be used as prognostic factors for outcomes of COVID-19. [ABSTRACT FROM AUTHOR]

• So far, a particular therapeutic option has not been approved for COVID-19. • Antiviral agents and immune modulating strategies has been studied for COVID-19 treatment. • Current treatments are diverse in each patient and have various outcomes. • Some novel approach such as cell based therapy, and immunotherapy may have significant potential in the COVID-19 treatment. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic and transmissible virus. Infection caused by SARS-CoV-2 known as Coronavirus disease 2019 (COVID-19) can be severe, especially among high risk populations affected of underlying medical conditions. COVID-19 is characterized by the severe acute respiratory syndrome, a hyper inflammatory syndrome, vascular injury, microangiopathy and thrombosis. Antiviral drugs and immune modulating methods has been evaluated. So far, a particular therapeutic option has not been approved for COVID-19 and a variety of treatments have been studied for COVID-19 including, current treatment such as oxygen therapy, corticosteroids, antiviral agents until targeted therapy and vaccines which are diverse in each patient and have various outcomes. According to the findings of different in vitro and in vivo studies, some novel approach such as gene editing, cell based therapy, and immunotherapy may have significant potential in the treatment of COVID-19. Based on these findings, this paper aims to review the different strategies of treatment against COVID-19 and provide a summary from traditional and newer methods in curing COVID-19. [ABSTRACT FROM AUTHOR]

The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents. [Display omitted] • Several natural products are reported highly effective in COVID-19 therapy. • Therapeutic potential, biochemical properties and mechanism of action of essential phytoconstituents are discussed. • The mechanism of action of a few effective phytoconstituents in COVID-19 therapy are highlighted. • These phytoconstituents represent a promising option for targeting SARS-CoV-2 pathogenesis. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged from Wuhan in China before it spread to the entire globe. It causes coronavirus disease of 2019 (COVID-19) where mostly individuals present mild symptoms, some remain asymptomatic and some show severe lung inflammation and pneumonia in the host through the induction of a marked inflammatory 'cytokine storm'. New and efficacious vaccines have been developed and put into clinical practice in record time, however, there is a still a need for effective treatments for those who are not vaccinated or remain susceptible to emerging SARS-CoV-2 variant strains. Despite this, effective therapeutic interventions against COVID-19 remain elusive. Here, we have reviewed potential drugs for COVID-19 classified on the basis of their mode of action. The mechanisms of action of each are discussed in detail to highlight the therapeutic targets that may help in reducing the global pandemic. The review was done up to July 2021 and the data was assessed through the official websites of WHO and CDC for collecting the information on the clinical trials. Moreover, the recent research papers were also assessed for the relevant data. The search was mainly based on keywords like Coronavirus, SARS-CoV-2, drugs (specific name of the drugs), COVID-19, clinical efficiency, safety profile, side-effects etc.This review outlines potential areas for future research into COVID-19 treatment strategies. • More than one year to the COVID-19 pandemic, still no effective drug treatment exists so far. • We have summarized the drugs showing both positive effect and negative effects for their future application. • Veklury (Remdesivir) is the only FDA-approved drug for adult and pediatric patients • Chloroquine, Hydroxychloroquine, Azithromycin, colchicine and Ivermectin has been removed from the list of potential drugs. • Tocilizumab and Sarilumab has been proven to work and are currently under trials. • Though, Remdesivir has been licensed for emergency and provisional use in different countries, it is not terribly effective. [ABSTRACT FROM AUTHOR]