ArticleLiterature Review

COVID-19: Pathophysiology, treatment options, nanotechnology approaches, and research agenda to combating the SARS-CoV2 pandemic

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  • Linguistics BHU
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Abstract

The recent corona virus disease (COVID-19) outbreak has claimed the lives of many around the world and highlighted an urgent need for experimental strategies to prevent, treat and eradicate the virus. COVID-19, an infectious disease caused by a novel corona virus and no approved specific treatment is available yet. A vast number of promising antiviral treatments involving nanotechnology are currently under investigation to aid in the development of COVID-19 drug delivery. The prospective treatment options integrating the ever-expanding field of nanotechnology have been compiled, with the objective to show that these can be potentially developed for COVID-19 treatment. This review summarized the current state of knowledge, research priorities regarding the pandemic and post COVID-19. We also focus on the possible nanotechnology approaches that have proven to be successful against other viruses and the research agenda to combat COVID-19.

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... This water-soluble, edible glue is used in food, pharmaceutical, and industrial applications. Why the gum Arabic is used as a moderating agent to prepare AgNPs is because GA exerts its components over NPs as capping agents change Zeta potential to negative and causes aggregation process [16]. Using GA as a growth medium for nickel nanoparticle preparation enhances excellent antibacterial behaviour [17]. ...
... The marginal shifts are seen between the peak value of IR spectra for GA and GA-AgNPs indicates that the gum Arabica has shared its functional molecules with AgNPs in various capacities like capping spot, surface-attached and stabilizing agents. The presence of phenols, alcohols, amides, sulfoxide, fla- vanoids, terpenoids and steroids etc. found in GA-AgNPs are also reported by other researchers [11][12][13][14][15][16]. ...
... The average size of NPs, width of Bragg's reflection at 111, and the corresponding average size of the GA-AgNPs, was found to be 11.0 nm. The presence of several unassigned peaks indicates that the GA-AgNPs have bio-organic compounds derived from gum Arabic on their surfaces, as reported by several other workers [11][12][13][14][15][16]. ...
Article
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Background Streptococcus mutans are an oral pathogen that causes dental caries, endocarditis, and systemic dysfunctions, an alternative antibacterial solution from silver nanoparticles (AgNPs) are investigated. Methods AgNPs were synthesized using the ethnobotanical product gum Arabic. It influenced the nanoparticles with medicinal value through their role as capping, stabilizing, or surface-attached components. The biophysical characteristics of the synthesized AgNPs were studied using UV–vis spectrum, XRD, EDAX, SEM, and TEM tools. The AgNPs were spherical with the average size less than 10 nm. By using the well diffusion and microdilution techniques, the impact of synthesized AgNPs was tested against S. mutans isolates. Results The smaller the size, the greater the antibacterial and antiviral potential the particles exhibit. The biophysical characteristics of AgNPs the presence of phenols, alcohols, amides, sulfoxide, flavanoids, terpenoids and steroids. The AgNPs exhibited a good antibacterial action against the oral pathogen S. mutans. The synthesized NPs at a dose level of 200 μg/mL exhibited an inhibition zone with 18.30 ± 0.5 nm diameter. The synthesised nanoparticles inhibited the genes responsible for biofilm formation of S. mutans over host tooth and gums (gtfB, gtfc, gtfD) and virulent protective factors (comDE, brpA and smu 360) and survival promoter genes (gyrA and spaP, gbpB). Conclusion The potent antibiotic action over S. mutans seen with the synthesized NPs, paves the way for the development of novel dental care products. Also, the small-sized NPs promote its applicability in COVID-19 pandemic containment.
...  TREATMENT FOR COVID19 USING NANOTECHNOLOGY: Several methods have been developed with the help of nanotechnology to deliver drugs more effectively. 1) Carbon nanotubes -RNA lyase-modified Carbon nanotubes in conjunction with photodynamic thermal effect have been experimented for COVID19 as the virus is sensitive to acidic environment and high temperature [8]. 2) Nanoviricidenanoviricides can dismantle the virus particle and attack the viral genome to destroy the virus completely without the help of the immune system [8]. ...
... 1) Carbon nanotubes -RNA lyase-modified Carbon nanotubes in conjunction with photodynamic thermal effect have been experimented for COVID19 as the virus is sensitive to acidic environment and high temperature [8]. 2) Nanoviricidenanoviricides can dismantle the virus particle and attack the viral genome to destroy the virus completely without the help of the immune system [8]. 3) Nanoparticles -Squalene nanoparticles have shown a reduction in the levels of pro-inflammatory cytokines and an increase in the levels of IL-10 in mice having cytokine storm when loaded with the anti-inflammatory drugs adenosine and alphatocopherol (vitamin E) [9]. ...
Preprint
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Ever since it’s advent, nanotechnology has played a very important role in the prevention, diagnosis and treatment of various diseases. Nanotechnology has been experimented to battle various challenges during this COVID19 pandemic like enhancing protection against the virus in the form of disinfectants and PPE, improved diagnostics and treatment options as well as in vaccine development. Summarized in this article are some of the ways in which nanotechnology has been experimented and used in the fight against COVID19.
... Covid-19 is a systemic multi-organ damage disease causing severe acute respiratory syndrome (SARS-CoV-2), which still causes significant death and disease in the world and continues to spread rapidly [3,11,12]. Regarding immunity to Covid-19, it is still not entirely clear what responses occur in Covid-19 and whether people recovering from Covid-19 infection are protected from a second infection [13][14][15]. With these clinical features of Covid-19, there is no specific treatment approved yet [13]. ...
... Regarding immunity to Covid-19, it is still not entirely clear what responses occur in Covid-19 and whether people recovering from Covid-19 infection are protected from a second infection [13][14][15]. With these clinical features of Covid-19, there is no specific treatment approved yet [13]. ...
Article
Since February-2020, the world has been battling a tragic public-health crisis with the emergence and spread of 2019-nCoV. Due to the lack of information about the pathogenesis-specific treatment of Covid-19, early diagnosis and timely treatment are important. However, there is still a lack of information about routine-blood-parameteres (RBP) findings and effects in the disease process. Although the literature includes various interventions, existing studies need to be generalized and their reliability improved. In this study, the efficacy of routine blood values used in the diagnosis and prognosis of Covid-19 and independent biomarkers obtained from them were evaluated retrospectively in a large patient group. Low lymphocyte (LYM) and white-blood-cell (WBC), high CRP and Ferritin were effective in the diagnosis of the disease. The d-CWL= CRPWBC∗LYM and d-CFL= CRP∗FerritinLYM biomarkers derived from them were the most important risk factors in diagnosing the disease and were more successful than direct RBP values. High d-CWL and d-CFL values largely confirmed the Covid-19 diagnosis. The most effective RBP in the prognosis of the disease was CRP. (d-CIT) = CRP*INR*Troponin; (d-CT) = CRP*Troponin; (d-PPT) = PT*Troponin*Procalcitonin biomarkers were found to be more successful than direct RBP values and biomarkers used in previous studies in the prognosis of the disease. Finally, an open-access data source consisting of RBC was created for studies to be carried out in the fight against COVİD-19. In this study, biomarkers derived from RBP were found to be more successful in both diagnosis and prognosis of Covid-19 than previously used direct RBP and biomarkers.
... Signaling transduction pathways are a chain of reactions that involve a complex ballet of molecules interacting and stimulating surrounding proteins, lipids and ions that culminate in the transmission of signals from the cell surface to a variety of intracellular targets including transcription factors. These molecular circuits detect, amplify, and integrate diverse external signals that result in changes in enzyme activity or ion-channel activity as a consequence of which induction of gene expression, cytoskeletal reorganization and modulation of differentiation occurs (Cooper, 2000;Berg et al., 2002b;Svoboda and Reenstra, 2002). Some of the important signaling pathways are the JAK/STAT, TLR, NF-κB, PI3K/AkT, mTOR, MAPK/ERK, AMPK, TGF beta, VEGF, and Notch signaling cascades. ...
... Nanotechnology has much to offer in the fight against the COVID-19 pandemic. The use of nanotechnology to deliver immunomodulatory drugs in COVID-19 will be advantageous; drug delivery to physiologically in-accessible sites is facilitated, specificity and targeting is improved, reduced drug distribution to non-target tissues minimizes possible side effects, the large surface-to-volume ratio of NP increases drug loading and the inherent virucidal activity of NP (gold/silver) is a bonus point (Bhavana et al., 2020;Palestino et al., 2020;Weiss et al., 2020). Some strategic guidelines for the development of nanotherapeutics to treat COVID-19 include an appropriate nanocarrier selection that will bypass the conventional limitations of the drug candidate, chemical altering/(re)engineering the drug molecule for improved compatibility with the nanocarrier and employing nanocarriers for multiple drug molecules (Chauhan et al., 2020). ...
Article
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The study of the use of nanotechnology for drug delivery has been extensive. Nanomedical approaches for therapeutics; drug delivery in particular is superior to conventional methods in that it allows for controlled targeted delivery and release, higher stability, extended circulation time, minimal side-effects, and improved pharmacokinetic clearance (of the drug) form the body, to name a few. The magnitude of COVID-19, the current ongoing pandemic has been severe; it has caused widespread the loss of human life. In individuals with severe COVID-19, immune dysregulation and a rampant state of hyperinflammation is observed. This kind of an immunopathological response is detrimental and results in rapid disease progression, development of secondary infections, sepsis and can be fatal. Several studies have pin-pointed the reason for this immune dysregulation; deviations in the signaling pathways involved in the mediation and control of immune responses. In severe COVID-19 patients, many signaling cascades including JAK/STAT, NF-κB, MAPK/ERK, TGF beta, VEGF, and Notch signaling were found to be either upregulated or inactivated. Targeting these aberrant signaling pathways in conjunction with antiviral therapy will effectuate mitigation of the hyperinflammation, hypercytokinemia, and promote faster recovery. The science of the use of nanocarriers as delivery agents to modulate these signaling pathways is not new; it has already been explored for other inflammatory diseases and in particular, cancer therapy. Numerous studies have evaluated the efficacy and potential of nanomedical approaches to modulate these signaling pathways and have been met with positive results. A treatment regime, that includes nanotherapeutics and antiviral therapies will prove effective and holds great promise for the successful treatment of COVID-19. In this article, we review different nanomedical approaches already studied for targeting aberrant signaling pathways, the host immune response to SARS-CoV-2, immunopathology and the dysregulated signaling pathways observed in severe COVID-19 and the current treatment methods in use for targeting signaling cascades in COVID-19. We then conclude by suggesting that the use of nanomedical drug delivery systems for targeting signaling pathways can be extended to effectively target the aberrant signaling pathways in COVID-19 for best treatment results.
... Metal nanoparticles such as gold nanoparticles (AuNP) and silver nanoparticles (AgNPs) are vastly examined nanotechnology method to treat viral infections. Several hypothesis of nanoparticles have been prepared to progress a new strategy to improve or eliminate the infection severity [127]. In recent research, it determined that colloidal Ag with particle sizes between 3-7 nm can be very effective to treat and prevent viral infection at early stage of respiratory infections [127]. ...
... Several hypothesis of nanoparticles have been prepared to progress a new strategy to improve or eliminate the infection severity [127]. In recent research, it determined that colloidal Ag with particle sizes between 3-7 nm can be very effective to treat and prevent viral infection at early stage of respiratory infections [127]. Sarkar and coworkers has hypothesized that the use of water dispersed AgNPs (10 nm) in combination with bronchodilators in lungs via bi-level ventilation or simple nebulizer machine may induce better virucidal action [128]. ...
Article
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The COVID-19 pandemic is currently an unprecedented public health threat. The rapid spread of infections has led to calls for alternative approaches to combat the virus. Nanotechnology is taking root against SARS-CoV-2 through prevention, diagnostics and treatment of infections. In light of the escalating demand for managing the pandemic, a comprehensive review that highlights the role of nanomaterials in the response to the pandemic is highly desirable. This review article comprehensively discusses the use of nanotechnology for COVID-19 based on three main categories: prevention, diagnostics and treatment. We first highlight the use of various nanomaterials including metal nanoparticles, carbon-based nanoparticles and magnetic nanoparticles for COVID-19. We critically review the benefits of nanomaterials along with their applications in personal protective equipment, vaccine development, diagnostic device fabrication and therapeutic approaches. The remaining key challenges and future directions of nanomaterials for COVID-19 are briefly discussed. This review is very informative and helpful in providing guidance for developing nanomaterial-based products to fight against COVID-19.
... Nanotechnology has huge potential for fighting the COVID-19 pandemic, since it enables targeted drug or vaccine delivery to physiologically inaccessible targets; increases drug loading and transport, and provides intrinsic/synergistic virucidal activity. 73,74 It can also possess simple, fast, and cost-effective alternative disinfection methods; provide targeted pulmonary drug delivery, and offer ways for designing better immunomodulating materials. It can generally contribute to antimicrobial, antiinflammatory, diagnostic, theranostic, therapeutic, biosensing, preventive/protective equipments, immunomodulation, and vaccination approaches against the pandemic. ...
... They can be formed in combination with each other or with inorganic NPs to form hybrid nanosystems based on specific use at the targeted site. 74 Inhalable organic and inorganic NPs ( Figure 6) 121 can be used for targeting the lung to overcome side effects from high serum concentrations of conventional administrations. 122 Nano-drug co-deliveries can reduce particle size-dependent safety issues in lung and respiratory systems. ...
Article
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A serious viral infectious disease was introduced to the globe by the end of 2019 that was seen primarily from China, but spread worldwide in a few months to be a pandemic. Since then, accurate prevention, early detection, and effective treatment strategies are not yet outlined. There is no approved drug to counter its worldwide transmission. However, integration of nanostructured delivery systems with the current management strategies has promised a pronounced opportunity to tackle the pandemic. This review addressed the various promising nanotechnology-based approaches for the diagnosis, prevention, and treatment of the pandemic. The pharmaceutical, pharmacoeconomic, and regulatory aspects of these systems with currently achieved or predicted beneficial outcomes, challenges, and future perspectives are also highlighted.
... Different immunomodulatory and antiinflammatory drugs such as tocilizumab (antirheumatic drug), chloroquine/hydroxychloroquine, and dexamethasone have been proposed to decrease or suppress the release/production of pro-inflammatory cytokines with the objective to minimize the cytokine storm associated with SARS-CoV-2 (Jamilloux et al., 2020;Zhao, 2020). Additionally, bacteriostatic macrolide antibiotics such as azithromycin, used against many Gram-positive and intracellular bacteria causing respiratory infections, demonstrate also immunomodulatory and anti-inflammatory effects (Bhavana et al., 2020;Pagliano et al., 2021). The prothrombotic effects of SARS-CoV-2 often manifested hypercoagulability and responsible of pulmonary thromboembolism, can be prevented by the prophylactic use of heparin (Pagliano et al., 2021). ...
... Besides, monoclonal antibodies against the S protein (e.g., gimsilumab, leronlimab) have been utilized in the treatment of COVID-19. By this mechanism, monoclonal antibodies reduce the cytokine storm in the pulmonary airway pathways and provides clinical symptomatic relief to patients from COVID-19 (Bhavana et al., 2020). Finally, convalescent plasma is a promising plasma antibody treatment that could help patients whose bodies cannot produce enough antibodies against COVID-19 to cure the disease (Won and Lee, 2020). ...
Article
Several medicinal products for human use are currently under consideration as potential treatment for COVID-19 pandemic. As proposals cover also prophylactic use, the treatment could be massive, resulting in unprecedent levels of antiviral emissions to the aquatic environment. We have adapted previous models and used available information for predicting the environmental impact of representative medicinal products, covering the main groups under consideration: multitarget antiparasitic (chloroquines and ivermectin), glucocorticoids, macrolide antibiotics and antiviral drugs including their pharmacokinetic boosters. The retrieved information has been sufficient for conducting a conventional environmental risk assessment for the group of miscellaneous medicines; results suggest low concern for the chloroquines and dexamethasone while very high impact for ivermectin and azithromycin, even at use levels well below the default value of 1% of the population. The information on the ecotoxicity of the antiviral medicines is very scarce, thus we have explored an innovative pharmacodynamic-based approach, combining read-across, quantitative structure-activity relationship (QSAR), US EPA's Toxicity Forecaster (ToxCast) in vitro data, pharmacological modes of action, and the observed adverse effects. The results highlight fish sublethal effects as the most sensitive target and identify possible concerns. These results offer guidance for minimizing the environmental risk of treatment medication for COVID-19.
... Recent water quality results which were obtained from various parts of the world showed positive signs on the existence of ribonucleic acid (RNA) of SARS-CoV-2 in the wastewater [159]. To date, the virus has been found in wastewater treatment plants that are located in Australia, China, the Czech Republic, Ecuador, France, Japan, Italy, Pakistan, Spain, Netherlands, USA, Turkey, and other countries [12,159,[161][162][163][164][165]). There were also published works that documented the presence of SARS-CoV-2 viruses in the treated wastewater [166,167]. ...
... The surveillance of wastewater for disease alert has gained growing interest and attention to remove viruses from wastewater efficiently [18,153,169]. Several works comprehensively discussed the occurrence and possible transmission of the SARS-CoV-2 virus through the water system [12,159,160,[163][164][165]. Briefly, the researchers revelated that the viruses enter the water system from the urine or stool of infected people and animals through various ways which include wastewater discharge from the hospitals, quarantine facilities, residential buildings, sewage, landfill, and drainage water. ...
Article
Consumption of pathogenic contaminated water has claimed the lives of many people. Hence, this scenario has emphasized the urgent need for research methods to avoid, treat and eliminate harmful pathogens in wastewater. Therefore, effective water treatment has become a matter of utmost importance. Membrane technology offers purer, cleaner, and pathogen-free water through the water separation method via a permeable membrane. Advanced membrane technology such as nanocomposite membrane, membrane distillation, membrane bioreactor, and photocatalytic membrane reactor can offer synergistic effects in removing pathogen through the integration of additional functionality and filtration in a single chamber. This paper also comprehensively discussed the application, challenges, and future perspective of the advanced membrane technology as a promising alternative in battling pathogenic microbial contaminants, which will also be beneficial and valuable in managing pandemics in the future as well as protecting human health and the environment. In addition, the potential of membrane technology in battling the ongoing global pandemic of coronavirus disease 2019 (COVID-19) was also discussed briefly.
... 348 Nanotechnology aspects developed for diabetic treatment might be adapted for COVID-19. 349 The large surface area, ciliated cells of lower respiratory tract may be ideal area for drug delivery as it is connected directly to systemic circulation via pulmonary administration with few challenges like branched nature of alveolar macrophages and pulmonary surfactant (phospholipids, proteins and mucins) decrease delivery efficiencies. However, the delivery to lower tract has to overcome muco-ciliary and cough clearance mechanisms. ...
... Inhalable PLGA, polycaprolactone or polylactic acid MPs might be the way for treatment, but their uses either for development or for improvement of an antiviral have been only partly investigated. 349 ...
Article
Monitoring blood glucose levels for diabetic patients is critical to achieve tight glycaemic control. As none of the current antidiabetic treatments restore lost functional β-cell mass in diabetic patients, insulin injections and the use of insulin pumps are most widely used in the management of glycaemia. The use of advanced and intelligent chemical engineering, together with the incorporation of micro- and nanotechnological-based processes have lately revolutionized diabetic management. The start of this concept goes back to 1974 with the description of an electrode that repeatedly measures the level of blood glucose and triggers insulin release from an infusion pump to enter the blood stream from a small reservoir upon need. Next to the insulin pumps, other drug delivery routes, including nasal, transdermal and buccal, are currently investigated. These processes necessitate competences from chemists, engineers-alike and innovative views of pharmacologists and diabetologists. Engineered micro and nanostructures hold a unique potential when it comes to drug delivery applications required for the treatment of diabetic patients. As the technical aspects of chemistry, biology and informatics on medicine are expanding fast, time has come to step back and to evaluate the impact of technology-driven chemistry on diabetics and how the bridges from research laboratories to market products are established. In this review, the large variety of therapeutic approaches proposed in the last five years for diabetic patients are discussed in an applied context. A survey of the state of the art of closed-loop insulin delivery strategies in response to blood glucose level fluctuation is provided together with insights into the emerging key technologies for diagnosis and drug development. Chemical engineering strategies centered on preserving and regenerating functional pancreatic β-cell mass are evoked in addition as they represent a permanent solution for diabetic patients.
... However, several medicines, including anti-viral, antimalarial, and anti-microbial medicines, as well as anti-bacterial medicines such as remdesivir, chloroquine, lopinavir/ritonavir, and hydroxychloroquine, are already available for use in treating COVID-19. 28 WHO also recommended oxygen therapy with extracorporeal membrane oxygenation (ECMO) method for all COVID-19 patients. 29 Several studies proved that ozone therapy has successfully treated various diseases caused by viruses, such as Ebola 30 and HIV/AIDS. ...
Article
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The current outbreak of Coronavirus disease 2019 (COVID-19) has become a health emergency of international concern since last December 2019. At the same time, the coronavirus pandemic also caused an economic crisis worldwide. All countries worldwide are competing to generate a qualified strategic plan for resolving this problem. Vaccine, treatment, and detection are the keys to control this pandemic. Global attempts to produce a suitable vaccine are ongoing in many laboratories. However, based on the failure of several previous vaccines, such as Ebola and dengue fever, has stimulated researchers to develop an effective and quick treatment. Effective treatment depends on the effectiveness of the detection method. Thus, a real-time, selective, and accurate detection method is urgently needed to detect if a person has been exposed to COVID-19. This paper is designed to discuss the current situation in controlling COVID-19 by several detection methods. The progress of each method is summarized and compared. Other information regarding the virus, such as the origin, transmission, and biomarkers of the virus, is also explained. The case progress of COVID-19 and its future directions also are discussed. © 2021 The Author(s). Published on behalf of The Electrochemical Society by IOP Publishing Limited.
... Among the highly pathogenic respiratory viruses SARS, MERS, and COVID-19, three strains of coronaviruses, have been recognized with variable clinical presentations and severity among humans. 1 To deliver their genome into the host cell, SARS-CoV2 are endocytosed prior to fusion with the cell membrane. Viral cellular internalization is triggered by the interaction between the protein viral spike (S) and the angiotensin-converting enzyme 2 (ACE2) receptor. ...
Article
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Global trials are grappling toward identifying prosperous remediation against the ever-emerging and re-emerging pathogenic respiratory viruses. Battling coronavirus, as a model respiratory virus, via repurposing existing therapeutic agents could be a welcome move. Motivated by its well-demonstrated curative use in herpes simplex and influenza viruses, utilization of the nanoscale zinc oxide (ZnO) would be an auspicious approach. In this direction, ZnO nanoparticles (NPs) were fabricated herein and relevant aspects related to the formulation such as optimization, structure, purity, and morphology were elucidated. In silico molecular docking was conducted to speculate the possible interaction between ZnO NPs and COVID-19 targets including the ACE2 receptor, COVID-19 RNA-dependent RNA polymerase, and main protease. The cellular internalization of ZnO NPs using human lung fibroblast cells was also assessed. Optimized hexagonal and spherical ZnO nanostructures of a crystallite size of 11.50 ± 0.71 nm and positive charge were attained. The pure and characteristic hexagonal wurtzite P63mc crystal structure was also observed. Interestingly, felicitous binding of ZnO NPs with the three tested COVID-19 targets, via hydrogen bond formation, was detected. Furthermore, an enhanced dose-dependent cellular uptake was demonstrated. The obtained results infer a rationale, awaiting validation from further biological and therapeutic studies.
... The clinical presentation of COVID-19 ranges from mild to severe symptoms; critical illness is characterized by respiratory failure, septic shock, and other multiple organ dysfunction or failure [4,5]. Patient characteristics, clinical outcomes, and resource use of hospitalized COVID -19 patients have been described in several US studies [6][7][8][9][10][11][12][13]. ...
Article
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Objective: To evaluate health outcomes and the economic burden of hospitalized COVID-19 patients in the United States. Methods: Hospitalized patients with a primary or secondary discharge diagnosis code for COVID-19 (ICD-10 code U07.1) from April 1 - October 31, 2020 were identified in the Premier Healthcare COVID-19 Database. Patient demographics, hospitalization characteristics, and concomitant medical conditions were assessed. Hospital length of stay (LOS), in-hospital mortality, hospital charges, and hospital costs were evaluated overall and stratified by age groups, insurance types, and 4 COVID-19 disease progression states based on intensive care unit (ICU) and invasive mechanical ventilation (IMV) usage. Results: Of the 173,942 hospitalized COVID-19 patients, median age was 63 years, 51.0% were male, and 48.5% were covered by Medicare. The most prevalent concomitant medical conditions were cardiovascular disease (73.5%), hypertension (64.8%), diabetes (40.7%), obesity (27.0%), and chronic kidney disease (24.2%). Approximately one-fifth (21.9%) of the hospitalized COVID-19 patients were admitted to the ICU and 16.9% received IMV; most patients (73.6%) did not require ICU admission or IMV, and 12.4% required both. The median hospital LOS was 5 days, in-hospital mortality was 13.6%, median hospital charges were $43,986, and median hospital costs were $12,046. Hospital LOS and in-hospital mortality increased with ICU and/or IMV usage and age; hospital charges and costs increased with ICU and/or IMV usage. Patients with both ICU and IMV usage had the longest median hospital LOS (15 days), highest in-hospital mortality (53.8%), and highest hospital charges ($198,394) and hospital costs ($54,402). Limitations: This retrospective administrative database analysis relied on coding accuracy and a subset of admissions with validated/reconciled hospital costs. Conclusions: This study summarizes the severe health outcomes and substantial hospital costs of hospitalized COVID-19 patients in the US. The findings support the urgent need for rapid implementation of effective interventions, including safe and efficacious vaccines.
... Nanotechnology-based approaches are one of the potential directions in combatting the pandemic. The potential advantages coming from the nature of the size and morphology of the nanoparticles, facilitate the drug delivery precision to minimize threats coming from the immune system response [39]. ...
... A recent study [23] proposed nanoparticle decoy targets preventing the virus from attaching to cells to reduce the possibilities of developing infection. Nanotechnological principles have helped to pioneer the creation of improved PPE and nanoscale drug delivery systems to overcome COVID-19 [5,20]. Furthermore, the utilisation of nanotechnology allows for the manipulation of the material's surface, allowing for hydrophobic and superhydrophobic designs. ...
Article
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It will be remembered in history as the event that brought the world together with science and technology; the COVID-19 pandemic has allowed for decades worth of progression in both healthcare policies and technology development. It has been a show of unprecedented global health policies ranging from the legal requirement for public facemask use to the use of tough movement restrictions that has bought the world’s economy to its knees. Here, we observe the impact of national lockdowns, facemask usage, and their effect on infection rates. It is clear that healthcare policies alone cannot tackle a pandemic. There is a huge pressure to develop personal protective equipment that not only has the capacity to prevent transmission but also has the ergonomics to be worn for long durations. In this work, we reveal our views and thoughts on the healthcare policies and developing materials and technology strategies that have contributed to reduce the damage of the pandemic, coming from the perspectives of materials scientists and a UK National Health Service consultant doctor.
... Nanomedicine has been successfully used to improve care in a wide variety of diseases such as neurological, cancer, cardiovascular, and infectious diseases, including HBV, HIV-1, respiratory syncytial virus, and influenza virus [57][58][59]. Nanotechnology may hold tremendous promise in the detection, treatment, and prevention of Covid-19 [60,61]. ...
Article
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Coronavirus disease (Covid-19) is a global pandemic. The Covid-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overloaded healthcare systems that need medication to be rapidly established, at least to minimize the incidence of Covid-19. The co-infection with other microorganisms has drastically affected human health. Due to the utmost necessity to treat the patient infected with Covid-19 earliest, poor diagnosis and misuse of antibiotics may lead the world where no more drugs are available even to treat mild infections. Besides, sanitizers and disinfectants used to help minimize widespread coronavirus infection risk also contribute to an increased risk of antimicrobial resistance. To ease the situation, zinc supplements' potentiality has been explored and found to be an effective element to boost the immune system. Zinc also prevents the entry of the virus by increasing the ciliary beat frequency. Furthermore, the limitations of current antiviral agents such as a narrow range and low bioavailability can be resolved using nanomaterials, which are considered an important therapeutic alternative for the next generation. Thus, the development of new antiviral nanoagents will significantly help tackle many potential challenges and knowledge gaps. This review paper provides profound insight into how Covid-19 and antimicrobial resistance (AMR) are interrelated and the possible implications and current strategies to fight the ongoing pandemic.
... The causative agent is a coronavirus which is presently known as SARS CoV2 [1][2][3]. The disease is named "COVID-19 [4][5][6][7][8][9][10]". The new disease manifests as an acute febrile respiratory infection. ...
Chapter
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COVID-19 is an important global problem. The disease causes illness and results in anxious state and panic. It also has a lot of socioeconomic impact worldwide. The supports for the affected persons are by several partners including religious unit. The religious unit can play important social welfare role to support the local people. In Indochina, many local Buddhist monasteries act this role. This is an interesting anthropological phenomenon. Many monasteries issue amulet as gimmicks for sale to the donor. The donor buys amulets for spiritual support during frustrate period and the monastery receive money for its welfare function. This is an interesting social sustainability phenomenon.
... In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. Therefore, we discuss the use of nanotechnology for COVID-19 virus management by the development of Nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and Nano-carrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing in this study [11][12][13][14][15][16][17][18]. Importantly, Nano-material based platform technologies may also play a key role in the distribution and administration of vaccines through micro-needle patches, single-dose slow-release implants, film-based vaccines, or by using plant viral nanoparticles for antigen delivery, which do not require cold chains. ...
Article
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The COVID-19 vaccine development involves high-tech platforms such as viral vectors, antigen carriers, and delivery technology. Nanotechnology tools can play a pivotal role in advancing COVID-19 treatment and vaccine design. Information related to the structural morphology of the SARS-CoV-2 virus, its pathophysiology, and related immunological response is the most important factor at the nanotechnology point of view. In the absence of a specific antiviral against SARS- CoV-2, present therapeutics target the multifaceted molecular interactions involved in viral infections and major comprises repurposing already existing antiviral molecules used for other RNA viruses. Furthermore, various kinds of vaccine candidate’s structure could be screened by using ma- chine learning. Recently, it is equally important to look for a suitable Nano-carrier delivery technology to make these repurposed therapeutics as well as new vaccine development safer and more effective affordable methodologies so that nanotechnology can reach patients.
... As stated by Udugama et al. [99], previous Not only limited to that, a recent study proposed usage of nanoparticles to create decoy targets for SARS-CoV-2 to attach, absorbing viruses and hindering their chance to contact cells to reduce the rate of developing an infection [105]. Moreover, previous studies reveal how nanotechnological approaches can reach out further by pioneering the creation of improved PPE and nano-sized drug delivery systems to overcome COVID-19 [106,107]. Among mentioned prevention methods which are the first line of defence for tackling the overwhelming course of the pandemic, the real challenge lies in vaccine development studies. ...
Article
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The recently emerged coronavirus pandemic (COVID-19) has become a worldwide threat affecting millions of people, causing respiratory system related problems that can end up with extremely serious consequences. As the infection rate rises significantly and this is followed by a dramatic increase in mortality, the whole world is struggling to accommodate change and is trying to adapt to new conditions. While a significant amount of effort is focused on developing a vaccine in order to make a game-changing anti-COVID-19 breakthrough, novel coronavirus (SARS-CoV-2) is also developing mutations rapidly as it transmits just like any other virus and there is always a substantial chance of the invented antibodies becoming ineffective as a function of time, thus failing to inhibit virus-to-cell binding efficiency as the spiked protein keeps evolving. Hence, controlling the transmission of the virus is crucial. Therefore, this review summarizes the viability of coronaviruses on inanimate surfaces under different conditions while addressing the current state of known chemical disinfectants for deactivation of the coronaviruses. The review attempts to bring together a wide spectrum of surface–virus–cleaning agent interactions to help identify material selection for inanimate surfaces that have frequent human contact and cleaning procedures for effective prevention of COVID-19 transmission.
... Based on the evidence from the clinical studies, the Remdesivir has been used to treat COVID-19, but the therapeutic effect remains very limited [7]. As a consequence, safe and effective therapy is urgently needed. ...
Article
The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised a global catastrophe. To date, there is no specific antiviral drug available to combat this virus, except the vaccine. In this study, the main protease (Mpro) required for SARS-CoV-2 viral replication was expressed and purified. Thirty-six compounds were tested as inhibitors of SARS-CoV-2 Mpro by fluorescence resonance energy transfer (FRET) technique. The half-maximal inhibitory concentration (IC50) values of Ebselen and Ebsulfur analogs were obtained to be in the range of 0.074-0.91 μM. Notably, the molecules containing furane substituent displayed higher inhibition against Mpro, followed by Ebselen 1i (IC50 = 0.074 μM) and Ebsulfur 2k (IC50 = 0.11 μM). The action mechanism of 1i and 2k were characterized by enzyme kinetics, pre-incubation and jump dilution assays, as well as fluorescent labeling experiments, which suggested that both compounds covalently and irreversibly bind to Mpro, while molecular docking suggested that 2k formed an S–S bond with the Cys145 at the enzymatic active site. This study provides two very potent scaffolds Ebsulfur and Ebselen for the development of covalent inhibitors of Mpro to combat COVID-19.
... For the protection of people "Prevention is always marked superior than cure" to fight against infectious, transmittable and communicable disease. Thus, as per the current scenario, to combat this unprecedented and promptly transmitting COVID-19 pandemic, only way is to follow precautionary measures well in advanced [18] . While researchers and clinical specialists are working day and night to build an antibody to fight infection, there is no complete solution to the infection from now on. ...
Article
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Face shield are the unmistakable plastic gatekeepers secures eyes and face, simpler to wear and a group of specialists state face shields may supplant masks as an increasingly agreeable and progressively successful obstacle to COVID-19. Face shields are useful in stopping respiratory droplets from speading from the wearer to others. The droplets, which come into contact with the shield, are quickly spread over a large area, both transversely and vertically, over the shield, but with a shrinking concentration of droplets, as opposed to face masks, which appear to slide under the nose of the wearer or, worse, collapse entirely off the shield. Hence, a face- shield can be considered as personal protective equipment (PPE), which is a first line of resistance, utilized by the clinicians and forefront health workers for protection against the infectious body fluid and aerosols. Face-shields are mainly fabricated using polycarbonate material, because of their excellent optical transparency in UVA-visible-IR spectrum and mechanical properties. The goal of this article is to provide researchers working in the same area, as well as health and industrial staff, with a detailed analysis of the usage of face shields against bioaerosols and the need for personal security. The reviews main focus on the background of the face shield, provide assistance in the selection, its design and structure, applications, advantages and disadvantages. Lastly, people's view about the usage of face shield as it becomes an essential part of human beings like an accomplice during this current pandemic situation.
... However, several medicines, including anti-viral, antimalarial, and anti-microbial medicines, as well as anti-bacterial medicines such as remdesivir, chloroquine, lopinavir/ritonavir, and hydroxychloroquine, are already available for use in treating COVID-19. 28 WHO also recommended oxygen therapy with extracorporeal membrane oxygenation (ECMO) method for all COVID-19 patients. 29 Several studies proved that ozone therapy has successfully treated various diseases caused by viruses, such as Ebola 30 and HIV/AIDS. ...
Article
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The current outbreak of Coronavirus disease 2019 (COVID-19) has become a health emergency of international concern since last December 2019. At the same time, the coronavirus pandemic also caused an economic crisis worldwide. All countries worldwide are competing to generate a qualified strategic plan for resolving this problem. Vaccine, treatment, and detection are the keys to control this pandemic. Global attempts to produce a suitable vaccine are ongoing in many laboratories. However, based on the failure of several previous vaccines, such as Ebola and dengue fever, has stimulated researchers to develop an effective and quick treatment. Effective treatment depends on the effectiveness of the detection method. Thus, a real-time, selective, and accurate detection method is urgently needed to detect if a person has been exposed to COVID-19. This paper is designed to discuss the current situation in controlling COVID-19 by several detection methods. The progress of each method is summarized and compared. Other information regarding the virus, such as the origin, transmission, and biomarkers of the virus, is also explained. The case progress of COVID-19 and its future directions also are discussed.
... within the beginning of the pandemic to August 2020. Table S1 (Supplementary material) presents a classification of the published reviews based on their main purposes: (i) reviews and minireviews about the main advances carried out in the diagnostic tests in the last months, together with a critical discussion about their utility [2,3,; (ii) information about the biosensors and the nanotechnology is presented as a useful tool to develop new strategies for the detection of the infection and also for its treatment [8,11,[54][55][56][57][58][59][60][61][62][63][64][65][66][67]; (iii) different point of view about how the artificial intelligence (AI) can be presented as a versatile tool to control the pandemic and, even more interesting, in containing the spread of the virus [20,68,69]; (iv) current and update information about the structure and genomic of SARS-CoV-2 [70][71][72][73][74][75][76][77][78][79]; (v) the treatments that are being applied to fight the infection and the type of vaccines that are being developed [80][81][82][83][84][85]; and (vi) finally the Table S1 (Supplementary material) collects two reviews that cannot be classified in the previous groups. They provide interesting information about de workflow that should be followed for the detection of the infection, as well as information about natural products that could have a positive effect in the prevention and treatment of the infection [86,87]. ...
Article
Since December 2019, we have been in the battlefield with a new threat to the humanity known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we describe the four main methods used for diagnosis, screening and/or surveillance of SARS-CoV-2: Real-time reverse transcription polymerase chain reaction (RT-PCR); chest computed tomography (CT); and different complementary alternatives developed in order to obtain rapid results, antigen and antibody detection. All of them compare the highlighting advantages and disadvantages from an analytical point of view. The gold standard method in terms of sensitivity and specificity is the RT-PCR. The different modifications propose to make it more rapid and applicable at point of care (POC) are also presented and discussed. CT images are limited to central hospitals. However, being combined with RT-PCR is the most robust and accurate way to confirm COVID-19 infection. Antibody tests, although unable to provide reliable results on the status of the infection, are suitable for carrying out maximum screening of the population in order to know the immune capacity. More recently, antigen tests, less sensitive than RT-PCR, have been authorized to determine in a quicker way whether the patient is infected at the time of analysis and without the need of specific instruments.
... Sarkar and participants estimated that the use of AgNPs dispersed water by mixing with bronchodilators in the lungs by inhaling a bilevel air or direct nebulizer machine may result in better viracidal activity. Finally, it is still high in the air that colloidal Ag with a molecular size between 3 and 7 nm can be very effective in treating and preventing bacterial infections at the beginning of the respiratory stage [90,91]. AgNPs have attractive colloid type that also includes active amine particles SiO 2 -Fe 3 O 4 indicating a promising nanosystem to block infection. ...
Article
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The global outbreak of coronavirus disease has sent an ominous message to the field of innovative and advanced technology research and development (COVID-19). To accomplish this, convectional technology and recent discoveries can be combined, or new research directions can be opened up using nanotechnology. Nanotechnology can be used to prevent, diagnose, and treat SARS-CoV-2 infection. As the pandemic spreads, a thorough examination of nanomaterials' role in pandemic response is highly desirable. According to this comprehensive review article, nanotechnology can be used to prevent, diagnose, and treat COVID-19. This research will be extremely useful during the COVID-19 outbreak in terms of developing rules for designing nanostructure materials to combat the outbreak.
... Some drugs have also been suggested to reduce the damage caused by SARS-CoV-2 to the lungs [8]. In some cases, plasma therapy is also suggested [13]. This method of treatment is used in patients who are not able to produce enough antibodies and is a safe and effective method and seems to reduce mortality [14]. ...
Article
Full-text available
Coronavirus is a beta virus that has caused a worldwide pandemic since December 2019. Many treatments such as antiviral drugs, immunosuppressive drugs, neutralizing antibodies, and monoclonal antibodies have been tested on coronavirus disease 2019 (COVID-19) that most of them were effective. Given that nanotechnology-based approaches have been successful in detection and treatment of viral systems such as human immunodeficiency virus (HIV), influenza A virus subtype H1N1 and Middle East respiratory syndrome coronavirus (MERS-CoV), they also seem to be effective in detecting and treating COVID-19. Nanotechnology is used in various methods for early and rapid diagnosis of the disease. Nanoparticles can be used in products for the diagnosis, treatment and prevention of COVID-19. These substances are very effective in the controlled delivery of antiviral drugs and biomolecules and they are also used in the manufacture of personal safety equipment, widely, and the production of anti-virus coatings for surfaces, air filters and the production of vaccines. In general, nanomaterial can play an important role in controlling the disease, based on strategies to prevent the virus from entering the host cell, inhibiting virus replication, virus delivery systems, and nano-based vaccines. Nanotechnology is a multidisciplinary tool that can offer a variety of solutions based on disease prevention, diagnosis and treatment strategies.
... The global outbreak and prevalence of COVID-19 caused by SARS-CoV-2 demands a protracted therapeutic intervention to control and mitigate the evolving pandemic [50]. Unfortunately, limited specific vaccines or targeted antiviral drugs or formulation are available to prevent (Pfizer-BioNTech COVID-19 vaccine, Moderna COVID-19 vaccine, and Janssen COVID-19 vaccine) [51], treat and manage such a highly infectious viral disease [52] with global cumulative statistics of 490,478 new cases, 124, 928, 590 confirmed cases and 2,746,180 deaths as of 25 th March 2021 [3]. ...
Article
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Nanoparticles (NPs) are projected to play a significant role in fighting against coronavirus disease (COVID-19). The various properties of NPs like magnetic and optical can be exploited to build diagnostic test kits. The unembellished morphological and physiochemical resemblances of SARS-CoV-2 with synthetic NPs make them a potent tool for mediation. Nanoparticles can be analytically functionalized with different proteins, polymers, and functional groups to perform specific inhibitory functions while also serving as delivery vehicles . Moreover, NPs can also be employed to prepare broad-spectrum respiratory drugs and vaccines that can guard seasonal flu and prepare the human race for the pandemic in the future. The present review outlines the role of NPs in detection, diagnostic and therapeutic against members of the coronavirus family. We emphasize nanomaterial-based approaches to address coronaviruses in general and SARS-CoV-2 in particular. We discuss NPs based detection systems like graphene (G-FET), biosensors, and plasmonic photothermal associated sensors. Inorganic, organic virus-like & self-assembly protein (VLP), and photodynamic inactivation of SARS-CoV-2 are also presented as therapeutic approaches exploiting NPs.
... Carbon-based nanomaterials such as graphene, carbon dots and fullerenes with physical and chemical properties such as strength, corrosion resistance, excellent electrical and thermal conductivity as well as stability also proves to show the antiviral properties (Innocenzi and Stagi 2020;Yu et al. 2021). In fact, these inorganic nanomaterials have been discussed to be used as the future management against COVID-19 that does not limit to diagnosis, vaccine and therapies development (Palestino et al. 2020;Bhavana et al. 2020;Yu et al. 2021). Thus, it is not surprising that inorganic nanomaterials are incorporated into the synthesis of effective antiviral PPE against COVID-19. ...
Article
The coronavirus disease 2019 (COVID-19) has caused a worldwide outbreak. The severe acute respiratory syndrome coronavirus 2 virus can be transmitted human-to-human through droplets and close contact where personal protective equipment (PPE) is imperative to protect the individuals. The advancement of nanotechnology with significant nanosized properties can confer a higher form of protection. Incorporation of nanotechnology into facemasks can exhibit antiviral properties. Nanocoating on surfaces can achieve self-disinfecting purposes and be applied in highly populated places. Moreover, nano-based hand sanitizers can confer better sterilizing efficacies with low skin irritation as compared to alcohol-based hand sanitizers. The present review discusses the incorporation of nanotechnology into nano-based materials and coatings in facemasks, self-surface disinfectants and hand sanitizers, in the hope to contribute to the current understanding of PPE to combat COVID-19.
... Carbon-based nanomaterials such as graphene, carbon dots and fullerenes with physical and chemical properties such as strength, corrosion resistance, excellent electrical and thermal conductivity as well as stability also proves to show the antiviral properties (Innocenzi and Stagi 2020;Yu et al. 2021). In fact, these inorganic nanomaterials have been discussed to be used as the future management against COVID-19 that does not limit to diagnosis, vaccine and therapies development (Palestino et al. 2020;Bhavana et al. 2020;Yu et al. 2021). Thus, it is not surprising that inorganic nanomaterials are incorporated into the synthesis of effective antiviral PPE against COVID-19. ...
Article
The coronavirus disease 2019 (COVID-19) has caused a worldwide outbreak. The severe acute respiratory syndrome coronavirus 2 virus can be transmitted human-to-human through droplets and close contact where personal protective equipment (PPE) is imperative to protect the individuals. The advancement of nanotechnology with significant nanosized properties can confer a higher form of protection. Incorporation of nanotechnology into facemasks can exhibit antiviral properties. Nanocoating on surfaces can achieve self-disinfecting purposes and be applied in highly populated places. Moreover, nano-based hand sanitizers can confer better sterilizing efficacies with low skin irritation as compared to alcohol based hand sanitizers. The present review discusses the incorporation of nanotechnology into nano-based materials and coatings in facemasks, self-surface disinfectants and hand sanitizers, in the hope to contribute to the current understanding of PPE to combat COVID-19.
... Nanomedicine has been used successfully to enhance treatment for a wide range of illnesses including neural, cancer, cardiopulmonary, and communicable diseases like HIV-1, HBV, influenza virus and respiratory syncytial virus [86][87][88][89][90][91]. Nanotechnology could play a potential role in diagnosis, treatment, and prevention of COVID-19 [92][93][94]. Furthermore, numerous CoV-related patents have been enrolled in the area of nanotechnology [86]. The global effect of the current pandemic is terrifying, and vaccine is the most effective option for preventing the transmission and combating novel CoV outbreaks [95]. ...
... On the one hand, measures were taken to reduce the spread of the virus, such as social isolation, wearing masks, public transportation regulations, and curfew; on the other hand, investigations were conducted to treat infected cases (2,3). Although many drugs have been used to manage the disease in the early days, there is still no definitive method to treat the infection (4). The high mortality rate in hospitalized patients, the long hospitalization period of the patients, the significant rate of patients in need of intensive care, and the extensive mortality have pointed that other resolutions should be queried. ...
Article
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Introduction: This study was aimed to define the demographic structure of vaccinated patients admitted to the emergency room (ER) with COVID-19 symptoms, and their hospitalization status, length of stay (LoS) in hospital, and mortality status. Material and Method: This research is a retrospective, cross-sectional and descriptive study. Furthermore, it includes the period between 15.01.2021 and 30.04.2021. Results: An 887 COVID-19 vaccinated patients who applied to ER. Of these, 383 (42.2%) were male, and 504 (56.8%) were female. The mean age of the patients was 52±18.6 years. The number of single-dose vaccinated patients was 696 (78.5%), and the two-dose vaccinated was 191 (21.5%). CoronaVac (Sinovac Life Sciences) vaccine was applied to 755 (85.1%), and BNT162b2 (Pfizer & Biontech) vaccine was applied to 132 (14.9%) patients before. In 317 (35.7%) cases, reverse transcription-polymerase chain reaction (Rt-PCR) positivity was detected in the ER application after vaccination. Of the total patients, 86 (9.7%) were hospitalized, 14 (1.4%) patients died in the hospital. The mean time between vaccination and application to ER was 25 (±21.9) days. Also, this period was 28.1 (±18) days in two�dose vaccinated patients. Conclusion: People who are vaccinated with the COVID-19 vaccine continue to have hospital admissions with COVID-19 symptoms. Rt-PCR positivity, need for hospitalization, and mortality may continue to be seen in vaccinated individuals. Keywords: Pandemic, COVID-19, vaccine, emergency room
... Although many drugs have been tried against the COVID-19, a definitive treatment could not be developed till now. 1 Due to the heavy burdon on economic, social, and health systems caused by the pandemic, it needs to be brought under control as soon as possible, for which vaccine development research commenced worldwide. 2 The vaccine for COVID-19 is required to protect from this disease, especially preventing severe morbidity and mortality, and reducing the need of hospitalization, the intensive care requirement, and shortening the length of stay (LoS) in the hospital. ...
Article
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Objective: This study examined COVID-19 Reporting and Data System (CO-RADS) scores, reverse transcription polymerase chain reaction (RT-PCR) positivity, and COVID-19 vaccination status of COVID-19 patients who reported to the emergency room (ER). Thus, it aimed to present how much effective the vaccines were. Methodology: It was a cross-sectional, retrospective, descriptive research, covering the period between Results: One hundred four cases were included in the study, of which 61 (58.7%) were male, and 43 (41.3%) were female. Of the patients, 35 (33.6%) had no COVID-19 vaccination, 46 (44.2%) had two-doses CoronaVac, one (1%) had two-doses BNT162b2. Out of 104 patients, 12 had a CO-RADS-3 score, 17 had a CO-RADS-4 score, and 60 patients had a CO-RADS-5 score. No significant difference was recognized between unvaccinated cases and vaccinated patients with two CoronaVac doses in terms of hospitalization, RT-PCR positivity and mortality (respectively: x2 = 0.176, SD = 1, p = 0.675; x2 = 0.025, SD = 1 , p = 0.874; x2 = 0.830, SD = 1, p = 0.362). Two doses CoronaVac vaccinated patients' length of stay in the hospital was determined to be more succinct than cases who had never been inoculated (U = 596.500, p = 0.045, z = 2.003, r =-0.22). Conclusion: Prolonged time after CoronaVac vaccination may reduce the vaccine's protection against COVID-19 pneumonia. The protection of two doses of BNT162b2 against COVID-19 pneumonia presents promise in the fight against the pandemic. Those inoculated with at least two doses of CoronaVac or BNT162b2 had a shorter hospital stay than those not vaccinated. RT-PCR positivity may continue to be observed in vaccinated patients.
... Further, NPs can be used as a carrier for antigens or as an adjuvant, and design new generation vaccines against COVID19 (Rai et al., 2021). As carbon nanoparticles are known for their inhibitory properties against various microorganisms, it would be essential to learn about their binding and inhibitory potential against SARS-CoV-2 targets (Bhavana et al., 2020). An interesting association between cancer and COVID-19 was illustrated to make it emergently effective for immunocompromised patients proposing the use of nanotechnology for vaccine development (Walls et al., 2020). ...
Article
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The present study aimed to predict the binding potential of carbon nanotube and nano fullerene towards multiple targets of SARS-CoV-2. Based on the virulent functions, the spike glycoprotein, RNA-dependent RNA polymerase, main protease, papain-like protease, and RNA binding domain of the nucleocapsid proteins of SARS-CoV-2 were prioritized as the molecular targets and their three-dimensional (3D) structures were retrieved from the Protein Data Bank. The 3D structures of carbon nanotubes and nano-fullerene were computationally modeled, and the binding potential of these nanoparticles to the selected molecular targets was predicted by molecular docking and molecular dynamic (MD) simulations. The drug-likeness and pharmacokinetic features of the lead molecules were computationally predicted. The current study suggested that carbon fullerene and nanotube demonstrated significant binding towards the prioritized multi-targets of SARS-CoV-2. Interestingly, carbon nanotube showed better interaction with these targets when compared to carbon fullerene. MD simulation studies clearly showed that the interaction of nanoparticles and selected targets possessed stability and conformational changes. This study revealed that carbon nanotubes and fullerene are probably used as effectual binders to multiple targets of SARS-CoV-2, and the study offers insights into the experimental validation and highlights the relevance of utilizing carbon nanomaterials as a therapeutic remedy against COVID-19.
... These limitations desperately urge scientists worldwide to investigate potential therapies. The main protease (M pro ) of SARS-CoV-2 offers a frequent target for developing specific anti-SARS-CoV-2 agents due to its considerable role in the viral life cycle, gene replication and expression [25][26][27]. ...
Article
Background/aim: SARS-CoV-2 is one of the coronavirus families that emerged at the end of 2019. It infected the respiratory system and caused a pandemic worldwide. Fluoroquinolones (FQs) have been safely used as antibacterial agents for decades. The antiviral activity of FQs was observed. Moreover, substitution on the C-7 position of ciprofloxacin enhanced its antiviral activity. Therefore, this study aims to investigate the antiviral activity of 7-(4-(N-substituted-carbamoyl-methyl)piperazin-1yl)-chalcone in comparison to ciprofloxacin against SARS-CoV-2 main protease (Mpro ). Materials and methods: Vero cells were infected with SARS-CoV-2. After treatment with ciprofloxacin and the chalcone at the concentrations of 1.6, 16, 160 nM for 48 hours, SARS-CoV-2 viral load was detected using real-time qPCR, SARS-CoV-2 infectivity was determined using plaque assay, and the main protease enzyme activity was detected using in vitro 3CL-protease inhibition assay. The activity of the chalcone was justified through molecular docking within SARS-CoV-2 Mpro , in comparison to ciprofloxacin. Results: The new chalcone significantly inhibited viral load replication where the EC50 was 3.93 nM, the plaque formation ability of the virus was inhibited to 86.8%±2.47. The chalcone exhibited a significant inhibitory effect against SARS-CoV-2 Mpro in vitro in a dose-dependent manner. The docking study into SARS-CoV-2 Mpro active site justified the importance of adding a substitution to the parent drug. Additionally, the assessment of the drug-likeness properties indicated that the chalcone might have acceptable ADMET properties. Conclusion: The new chalcone might be useful and has new insights for the inhibition of SARS-CoV-2 Mpro .
... COVID-19 is transmitted to healthy individuals through small airborne droplets exhaled by an infected person, personal contact (shaking hands), and by touching contaminated surfaces [5,6]. The ingestion of droplets into the lungs leads to lower respiratory tract infections ranging from mild respiratory infections to severe acute respiratory syndrome [7]. ...
Article
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Coronavirus disease-2019 (COVID-19) is caused by coronavirus-2 (SARS-CoV-2) and has produced a global pandemic. As of 22 June 2021, 178 million people have been affected worldwide, and 3.87 million people have died from COVID-19. According to the Centers for Disease Control and Prevention (CDC) of the United States, COVID-19 virus is primarily transmitted between people through respiratory droplets and contact routes. Since the location of initial infection and disease progression is primarily through the lungs, the inhalation delivery of drugs directly to the lungs may be the most appropriate route of administration for treating COVID-19. This review article aims to present possible inhalation therapeutics and vaccines for the treatment of COVID-19 symptoms. This review covers the comparison between SARS-CoV-2 and other coronaviruses such as SARS-CoV/MERS, inhalation therapeutics for the treatment of COVID-19 symptoms, and vaccines for preventing infection, as well as the current clinical status of inhaled therapeutics and vaccines.
... Nanomedicine has been used successfully to enhance treatment for a wide range of illnesses including neural, cancer, cardiopulmonary, and communicable diseases like HIV-1, HBV, influenza virus, and respiratory syncytial virus (Ahmad et al., 2014b;Ghosh et al., 2019Ghosh et al., , 2021aAbd Ellah et al., 2020;Srivastava et al., 2021). Nanotechnology could play a potential role in diagnosis, treatment, and prevention of COVID-19 (Bhavana et al., 2020;Campos et al., 2020;Noori et al., 2020). Furthermore, numerous CoV-related patents have been enrolled in the area of nanotechnology (Abd Ellah et al., 2020). ...
Article
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The ongoing coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, was triggered and unfolded quickly throughout the globe by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new virus, transmitted primarily through inhalation or contact with infected droplets, seems very contagious and pathogenic, with an incubation period varying from 2 to 14 days. The epidemic is an ongoing public health problem that challenges the present global health system. A worldwide social and economic stress has been observed. The transitional source of origin and its transport to humans is unknown, but speedy human transportation has been accepted extensively. The typical clinical symptoms of COVID-19 are almost like colds. With case fatality rates varying from 2 to 3 percent, a small number of patients may experience serious health problems or even die. To date, there is a limited number of antiviral agents or vaccines for the treatment of COVID-19. The occurrence and pathogenicity of COVID-19 infection are outlined and comparatively analyzed, given the outbreak’s urgency. The recent developments in diagnostics, treatment, and marketed vaccine are discussed to deal with this viral outbreak. Now the scientist is concerned about the appearance of several variants over the globe and the efficacy of the vaccine against these variants. There is a need for consistent monitoring of the virus epidemiology and surveillance of the ongoing variant and related disease severity.
... Potential antiviral drugs currently being used for treatment are lopinavir, ritonavir, remdesivir, umifenovir, oseltamivir, tenofovir disoproxil and lamivudine and interferon β -1a [2,3]. ...
Article
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Background: An outbreak of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection or COVID 19 has caused serious threats to all around the world. Until an effective and safe vaccine for novel coronavirus is developed by scientists, current drug therapy should be optimized for the control and treatment of COVID 19. Objective: In this manuscript, we present a perspective on possible benefits of reformulating antiviral drug dosage form with nanoemulsion system against novel coronavirus infection. Methods: Literature review has been done on COVID 19, treatment strategies, novel drug delivery systems and the role of pulmonary surfactant in lung protection. Results: Nanoemulsion system and its components have certain biophysical properties which could increase the efficacy of drug therapy. Antiviral drugs, delivered through a nanoemulsion system containing P-gp inhibitor (surfactant and co-solvent), can minimize the cellular resistance to drugs and would potentiate the antiviral action of drugs. Pulmonary Surfactant (PS) assisted antiviral drug delivery by nanoemulsion system could be another effective approach for the treatment of COVID 19. The use of functional excipients like Pulmonary Surfactant (PS) and Surfactant Proteins (SPs) in the formulation of the antiviral drug-loaded nanoemulsion system can improve the treatment of coronavirus infection. Conclusion: In our opinion, for synergizing antiviral action, lipid and protein portion of PS and their commercial analogs should be explored by pharmaceutical scientists to use them as a functional excipi-ent in the formulation of antiviral drug-loaded nanoemulsion system.
... Researchers and physicians are making efforts to provide proper treatment for COVID-19 patients [162]. Researchers are testing a wide range of possible therapies, including antiviral medicines, immunosuppressants, monoclonal antibodies, and vaccines [163]. In the early stages of the disease, the patient's immune system is challenged to prevent replication of the SARS-CoV-2 virus; however, in the acute stages, maybe experience tissue damage due to severe immune/inflammatory reactions [164]. ...
Article
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Coronaviruses belong to the “Coronaviridae family”, which causes various diseases, from the common cold to SARS and MERS. The coronavirus is naturally prevalent in mammals and birds. So far, six human-transmitted coronaviruses have been discovered. Severe acute res- piratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China. Common symptoms include fever, dry cough, and fatigue, but in acute cases, the disease can lead to severe shortness of breath, hypoxia, and death. According to the World Health Orga- nization (WHO), the three main transmission routes, such as droplet and contact routes, airborne transmission and fecal and oral for COVID-19, have been identified. So far, no definitive curative treatment has been discovered for COVID-19, and the available treatments are only to reduce the complications of the disease. According to the World Health Organization, preventive measures at the public health level such as quarantine of the infected person, identification and monitoring of contacts, disinfection of the environment, and personal protective equipment can significantly prevent the outbreak COVID-19. Currently, based on the urgent needs of the community to control this pandemic, the BNT162b2 (Pfizer), mRNA-1273 (Moderna), CoronaVac (Sinovac), Sputnik V (Gamaleya Research Institute, Acellena Contract Drug Research, and Development), BBIBP-CorV (Sinofarm), and AZD1222 (The University of Oxford; AstraZeneca) vaccines have received emergency vaccination licenses from health organizations in vaccine-producing countries. Vasso Apostolopoulos, Majid Hassanzadeganroudsari
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Penyakit menular akibat virus merupakan salah satu masalah kesehatan global yang mempengaruhi sistem kesehatan masyarakat dan ekonomi di seluruh dunia. Hal tersebut mendorong disusunnya artikel ini untuk mendiskusikan relevansi dan pentingnya imunoterapi dalam menentukan pilihan terapetik terkait infeksi virus, dengan menitikberatkan pembahasan pada ketersediaan pilihan vaksin dan obat yang telah ditemukan untuk membantu manusia melawan berbagai jenis infeksi yang disebabkan oleh virus. Penulisan artikel review naratif ini dilakukan menggunakan metode analisis pustaka primer maupun sekunder terkait yang berhasil dikumpulkan dari database online Google Scholar dan NCBI-PubMed. Selain itu, sumber acuan pustaka juga diambil dari beberapa buku teks akademik. Imunoterapi merupakan bidang yang berkembang melalui interaksi bidang imunologi, farmakologi dan farmakoterapi yang memiliki perkembangan yang pesat terutama dalam kondisi pandemi COVID-19 yang dihadapi saat ini. Meskipun terapi dan obat-obatan yang digunakan dalam bidang imunofarmakologi masih terbatas serta banyak hal yang belum dapat ditemukan, namun teknologi baru dan kemajuan pesat dalam pengetahuan tentang regulasi sistem imun telah menjadikan imunofterapi sebagai bidang yang memiliki potensi besar dan menjanjikan dalam penanganan infeksi virus maupun patogen lain. Oleh karena itu, konsep imunoterapi serta relevansinya dengan penyakit manusia merupakan salah satu solusi yang menawarkan pilihan baru untuk kebutuhan medis yang belum terpenuhi terkait penyakit infeksi akibat virus.
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Post-COVID syndrome also known as long COVID refers to symptoms persisting for more than three weeks after the diagnosis of COVID-19. We reviewed the current evidence on post-COVID syndrome, focusing on its clinical manifestations and addressing the challenges for its management in primary healthcare. The incidence of post-COVID syndrome is estimated at 10–35%, while for hospitalized patients it may reach 85%. Fatigue is the most common symptom reported in 17.5–72% of post-COVID cases, followed by residual dyspnea with an incidence ranging from 10–40%. Mental problems, chest pain, and olfactory and gustatory dysfunction may affect up to 26%, 22% and 11% of patients, respectively. More than one third of patients with post-COVID syndrome have pre-existing comorbidities, hypertension and diabetes mellitus being the most common. Beyond the prolonged duration of symptoms, the scarce published data indicate that most patients with post-COVID syndrome have a good prognosis with no further complications or fatal outcomes reported. Given the clinical spectrum of patients with post-COVID syndrome, most of them will be managed by primary healthcare professionals, in conjunction with pre-existing or new co-morbidities, which, in turn, may increase the burden of COVID-19 on primary healthcare. In conclusion approximately 10% of patients with COVID-19 may have symptoms persisting beyond three weeks, fulfilling the criteria of post-COVID syndrome. Primary healthcare professionals have a key role in the management of patients with post-COVID syndrome. Research is needed to elucidate the pathogenesis, clinical spectrum, and prognosis of post-COVID syndrome.
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Though already marketed antiviral drugs are used in the research to treat SARS CoV2 infection, the FDA approved drug and vaccine is still under different phases of clinical trials.
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Introduction Emerging evidence has shown that COVID-19 infection may result in right ventricular (RV) disturbance and be associated with adverse clinical outcomes. The aim of this meta-analysis is to summarise the incidence, risk factors and the prognostic effect of imaging RV involvement in adult patients with COVID-19. Methods A systematical search will be performed in PubMed, EMBase, ISI Knowledge via Web of Science and preprint databases (MedRxiv and BioRxiv) (until October 2021) to identify all cohort studies in adult patients with COVID-19. The primary outcome will be the incidence of RV involvement (dysfunction and/or dilation) assessed by echocardiography, CT or MRI. Secondary outcomes will include the risk factors for RV involvement and their association with all-cause mortality during hospitalisation. Additional outcomes will include the RV global or free wall longitudinal strain (RV-GLS or RV-FWLS), tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and RV diameter. Univariable or multivariable meta-regression and subgroup analyses will be performed for the study design and patient characteristics (especially acute or chronic pulmonary embolism and pulmonary hypertension). Sensitivity analyses will be used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of RV involvement incidence and related risk factors, association with all-cause mortality, and other RV parameters (RV-GLS or RV-FWLS, TAPSE, S’, FAC and RV diameter). Both linear and cubic spline regression models will be used to explore the dose–response relationship between different categories (>2) of RV involvement and the risk of mortality (OR or HR). Ethics and dissemination There was no need for ethics approval for the systematic review protocol according to the Institutional Review Board/Independent Ethics Committee of Fuwai Hospital. This meta-analysis will be disseminated through a peer-reviewed journal for publication. PROSPERO registration number CRD42021231689.
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Cytokine storm in coronavirus disease 2019 (COVID-19) patients leads to acute lung injury, acute respiratory distress syndrome, multiorgan dysfunction, shock, and thrombosis thus contributing to significant morbidity and mortality. Several agents like steroids, ascorbic acid, vitamins (C, D, E), glutathione, N-acetylcysteine have been used and several studies are underway to identify its efficacy in addressing undesirable effects due to COVID-19 illness. Among several experimental modalities based on expert opinion and anecdotal data, melatonin is one molecule that appears promising. Owing to its anti-inflammatory, anti-oxidant, and immunomodulatory properties, melatonin can be an important agent used as a component of multimodal analgesia in COVID-19 patients, suspected patients, and patients with exposure to positive patients undergoing emergency or urgent surgeries. Further research is required to know the optimal time of initiation, dose, and duration of melatonin as an adjunct.
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Since the first reports that the novel coronavirus was showing human-to-human transmission characteristics and asymptomatic cases, the number of patients with associated pneumonia has continued to rise and the epidemic has grown. It now threatens the health and lives of people across the world. The governments of many countries have attached great importance to the prevention of SARS-CoV-2, via research into the etiology and epidemiology of this newly emerged disease. Clinical signs, treatment, and prevention characteristics of the novel coronavirus pneumonia have been receiving attention worldwide, especially from medical personnel. However, owing to the different experimental methods, sample sizes, sample sources, and research perspectives of various studies, results have been inconsistent, or relate to an isolated aspect of the virus or the disease it causes. Currently, systematic summary data on the novel coronavirus are limited. This review combines experimental and clinical evidence into a systematic analysis and summary of the current progress of research into SARS-CoV-2, from multiple perspectives, with the aim of gaining a better overall understanding of the disease. Our report provides important information for current clinicians, for the prevention and treatment of COVID-19 pneumonia.
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A global epidemic caused by highly transmittable COVID-19 is causing severe loss of human life. In this study, two aspects of reducing transmission of COVID-19 virus, due to surface contact, are discussed: first refers to the effect of nanocarbon fullerene C60 coating on surface, that causes lipid peroxidation on the phospholipid layer present in the outer envelope of COVID-19; the second aspect refers to creating hydrophobic surfaces by texturing them, so that the contact area between virus and surface is minimized due to the presence of entrapped air between the topographies. These can be similar to micro-/nano-multiscale textured surfaces that have anti-biofouling properties. Fullerene-coated surfaces can be seen as a possible solution to decrease the adhesion of virus on the surface, as they will be hydrophobic as well as toxic to the envelope.
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The ongoing outbreak of the novel coronavirus pneumonia COVID-19 has caused great number of cases and deaths, but our understanding about the pathogen SARS-CoV-2 remains largely unclear. The attachment of the virus with the cell-surface receptor and a co-factor is the first step for the infection. Here, bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures have revealed the high affinity between human dipeptidyl peptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 are identical to those as bound to the MERS-CoV-S. Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with SARS-CoV-S. This potential utilization of DPP4 as a binding target for SARS-CoV-2 may offer novel insight into the viral pathogenesis, and help the surveillance and therapeutics strategy for meeting the challenge of COVID-19.
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On the 30 th of January 2020, the World Health Organization fired up the sirens against a fast spreading infectious disease caused by a newly discovered Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and gave this disease the name COVID-19. While there is currently no specific treatment for COVID-19, several off label drugs approved for other indications are being investigated in clinical trials across the globe. In the last decade, theranostic nanoparticles were reported as promising tool for efficiently and selectively deliver therapeutic moieties (i.e. drugs, vaccines, siRNA, peptide) to target sites of infection. In addition, they allow monitoring infectious sides and treatment responses using noninvasive imaging modalities. While intranasal delivery was proposed as the preferred administration route for therapeutic agents against viral pulmonary diseases, NP-based delivery systems offer numerous benefits to overcome challenges associated with mucosal administration, and ensure that these agents achieve a concentration that is many times higher than expected in the targeted sites of infection while limiting side effects on normal cells. In this article, we have shed light on the promising role of nanoparticles as effective carriers for therapeutics or immune modulators to help in fighting against COVID-19.
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Global health is facing the most dangerous situation regarding the novel severe acute respiratory syndrome called coronavirus 2 (SARS-CoV-2) and is widely known as abbreviated COVID-19 pandemic. This is due to the highly infectious nature of the disease and the possibility to cause pneumonia induced death in approximately 7% of infected individuals (data until 24 April 2020). The pathogen causing COVID-19 is called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is believed to be originated from the Wuhan Province in China. Unfortunately, an effective and approved vaccine for SARS-CoV-2 virus is still not available making the situation more dangerous and available medical care futile. This unmet medical need thus requires significant and very urgent research attention to develop effective vaccine to address the SARS-CoV-2 virus. In this review, the state-of-the-art drug design strategies against the virus are critically summarized including exploitations of novel drugs and potentials of repurposed drugs. The applications of nanochemistry and generally nanotechnology were also discussed to give the status of nanodiagnostic systems for COVID-19.
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A pneumonia outbreak with unknown etiology was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. The causative agent of the outbreak was identified by the WHO as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), producing the disease named coronavirus disease-2019 (COVID-19). The virus is closely related (96.3%) to bat coronavirus RaTG13, based on phylogenetic analysis. Human-to-human transmission has been confirmed even from asymptomatic carriers. The virus has spread to at least 200 countries, and more than 1,700,000 confirmed cases and 111,600 deaths have been recorded, with massive global increases in the number of cases daily. Therefore, the WHO has declared COVID-19 a pandemic. The disease is characterized by fever, dry cough, and chest pain with pneumonia in severe cases. In the beginning, the world public health authorities tried to eradicate the disease in China through quarantine but are now transitioning to prevention strategies worldwide to delay its spread. To date, there are no available vaccines or specific therapeutic drugs to treat the virus. There are many knowledge gaps about the newly emerged SARS-CoV-2, leading to misinformation. Therefore, in this review, we provide recent information about the COVID-19 pandemic. This review also provides insights for the control of pathogenic infections in humans such as SARS-CoV-2 infection and future spillovers.
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There are no effective antiviral drugs available against the pandemic causing COVID 19 virus. The complex protein - protein interaction between the virus and host is yet to be determined for designing of precise antiviral drugs against corona virus. The pandemic had claimed several thousand lives and had resulted most devastating effects on our mankind. In this scenario a potent drug is needed which will kill the viruses with minimal side effects on human body. Here I propose a novel antiviral therapy for effective killing of COVID19 with minimal side effects.
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The present outbreak associated with corona virus [CoVs] in China which is believed to be one of the massive eruptions towards mankind in 2019–2020. In the present scenario CoVs has been transmitted to the European and American regions through the travellers from wide spread countries like China and Japan. The viral disease is spreading through the contact in any form by the infected persons or patients and creating huge risk of mortality. CoVs are a single positive-sense RNA virus; mutation rates are higher than DNA viruses and indicate a more effective survival adaption mechanism. Human CoVs can cause common cold and influenza-like illness and a variety of severe acute respiratory disease such as pneumonia. Early in infection, CoVs infects epithelial cells, macrophages, T-cells, dendritic cells and also can affect the development and implantation of pro-inflammatory cytokines and chemokines. It mainly produces the melanoma differentiation associated with protein-5, retinoic acid inducible gene-1 and endosomal toll-like receptor 3. How CoVs affects the function of the immune system is still unclear due to lack of this knowledge. No Food and Drug Administration approved treatment is available till date. In this review, we are tried to explore the epidemiology, pathogenesis and current treatment of CoVs infection. The promising therapeutics molecules against CoVs and future prospective have been also discussed which will be helpful for researchers to find out the new molecules for the treatment of CoVs disease.
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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a potentially fatal disease of great global public health importance. As of March 26, 2020, the outbreak of COVID-19 has resulted in 462,801 confirmed cases and 20,839 deaths globally, which is more than those caused by SARS and Middle East respiratory syndrome (MERS) in 2003 and 2013, respectively. The epidemic has posed considerable challenges worldwide. Under a strict mechanism of massive prevention and control, China has seen a rapid decrease in new cases of coronavirus; however, the global situation remains serious. Additionally, the origin of COVID-19 has not been determined and no specific antiviral treatment or vaccine is currently available. Based on the published data, this review systematically discusses the etiology, epidemiology, clinical characteristics, and current intervention measures related to COVID-19 in the hope that it may provide a reference for future studies and aid in the prevention and control of the COVID-19 epidemic.
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COVID-19 has now been declared a pandemic. To date, COVID-19 has affected over 944,181 people worldwide, resulting in over 47,312 reported deaths. Numerous preventative strategies and non-pharmaceutical interventions have been employed to mitigate the spread of disease including careful infection control, the isolation of patients, and social distancing. Management is predominantly focused on the provision of supportive care, with oxygen therapy representing the major treatment intervention. Medical therapy involving corticosteroids and antivirals have also been encouraged as part of critical management schemes. However, there is at present no specific antiviral recommended for the treatment of COVID-19, and no vaccine is currently available. Despite the strategic implementation of these measures, the number of new reported cases continues to rise at a profoundly alarming rate. As new findings emerge, there is an urgent need for up-to-date management guidelines. In response to this call, we review what is currently known regarding the management of COVID-19, and offer an evidence-based review of current practice.
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Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.
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In early December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan City, Hubei Province, China. On January 30, 2020 the World Health Organization declared the outbreak as a Public Health Emergency of International Concern. As of February 14, 2020, 49,053 laboratory-confirmed and 1,381 deaths have been reported globally. Perceived risk of acquiring disease has led many governments to institute a variety of control measures. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In this literature review, the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and preventions strategies are all reviewed.
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Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 10 ⁹ /L vs. 0.76 × 10 ⁹ /L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.
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Posttraumatic stress symptoms and attitude toward crisis mental health services among clinically stable patients with COVID-19 in China - Hai-Xin Bo, Wen Li, Yuan Yang, Yu Wang, Qinge Zhang, Teris Cheung, Xinjuan Wu, Yu-Tao Xiang
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Over the last two decades, the world experienced three outbreaks of coronaviruses with elevated morbidity rates. Currently, the global community is facing emerging virus SARS-CoV-2 belonging to Betacoronavirus, which appears to be more transmissible but less deadly than SARS-CoV. The current study aimed to track the evolutionary ancestors and different evolutionary strategies that were genetically adapted by SARS-CoV-2. Our whole-genome analysis revealed that SARS-CoV-2 was the descendant of Bat SARS/SARS-like CoVs and bats served as a natural reservoir. SARS-CoV-2 used mutations and recombination as crucial strategies in different genomic regions including the envelop, membrane, nucleocapsid, and spike glycoproteins to become a novel infectious agent. We confirmed that mutations in different genomic regions of SARS-CoV-2 have specific influence on virus reproductive adaptability, allowing for genotype adjustment and adaptations in rapidly changing environments. Moreover, for the first time we identified nine putative recombination patterns in SARS-CoV-2, which encompass spike glycoprotein, RdRp, helicase and ORF3a. Six recombination regions were spotted in the S gene and are undoubtedly important for evolutionary survival, meanwhile this permitted the virus to modify superficial antigenicity to find a way from immune reconnaissance in animals and adapt to a human host. With these combined natural selected strategies, SARS-CoV-2 emerged as a novel virus in human society.
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Infectious diseases remain a leading cause of concern worldwide. Conventional vaccine methods to elicit immune responses have limitations in effectively controlling new and re-merging pathogens. Nanoparticle-based vaccines show promise in overcoming these limitations due to their versatility and tunability to protect antigen from premature degradations, facilitate their intracellular uptakes and elicit prolonged immunity against infectious diseases. Nanoparticle can be categorized as purely organic or inorganic based on the components that construct the structure. Most organic materials are biocompatible, biodegradable, and nontoxic, while most inorganic materials have a smaller particle size, improved stability, controlled tunability, enhanced permeability, high antigen loadings, and a triggered release profile. This review will focus on the different type of organic and inorganic nanoparticles used as vaccine against infectious diseases.
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The outbreak of Coronavirus Disease 2019 (COVID-19) causing novel coronavirus-infected pneumonia (NCIP), has affected the lives of 71,429 people globally. Originating in China, the disease has a rapid progression to other countries. Research suggests remarkable genomic resemblance of 2019-nCoV with Severe Acute Respiratory Syndrome (SARS) which has a history of a pandemic in 2002. With evidence of nosocomial spread, a number of diligent measures are being employed to constrain its propagation. Hence, the Public Health Emergency of International Concern (PHEIC) has been established by the World Health Organization (WHO) with strategic objectives for public health to curtail its impact on global health and economy.
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The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.
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An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its caused coronavirus disease 2019 (COVID-19) has been reported in China since December 2019. More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was about 1%–2%. No specific treatment has been reported. Herein, we examine the effects of Favipiravir (FPV) versus Lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million U twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million U twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance time was found for the FPV arm versus the control arm (median (interquartile range, IQR), 4 (2.5–9) d versus 11 (8–13) d, P < 0.001). The FPV arm also showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest imaging. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse reactions were found in the FPV arm than in the control arm. In this open-label nonrandomized control study, FPV showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance; if causal, these results should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection.
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In late December 2019, a cluster of unexplained pneumonia cases has been reported in Wuhan, China. A few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the relevant infected disease has been named as coronavirus disease 2019 (COVID‐19) by the World Health Organization respectively. The COVID‐19 epidemic is spreading in China and all over the world now. The purpose of this review is primarily to review the pathogen, clinical features, diagnosis, and treatment of COVID‐19, but also to comment briefly on the epidemiology and pathology based on the current evidences. This article is protected by copyright. All rights reserved.
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Abstract An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.
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Objective To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). Design Retrospective case series. Setting Seven hospitals in Zhejiang province, China. Participants 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020. Main outcome measures Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification. Results Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days. Conclusion As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.
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The outbreak of a novel betacoronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development, we determined a 3.5 Å-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.
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Teaser: Our review found the average R0 for 2019-nCoV to be 3.28, which exceeds WHO estimates of 1.4 to 2.5.
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Background: To explore the cellular immunity and cytokines status of NCP patients and to predict the correlation between the cellular immunity levels, cytokines and the severity of patients. Methods: 123 NCP patients were divided into mild and severe groups. Peripheral blood was collected, lymphocyte subsets and cytokines were detected. Correlation analysis was performed on the lymphocyte subsets and cytokines, and the differences between the indexes of the two groups were analyzed. Results: 102 mild and 21 severe patients were included. Lymphocyte subsets were reduced in two groups. The proportion of CD8 + T reduction in the mild and severe group was 28.43% and 61.9%, respectively; The proportion of B cell reduction was 25.49% and 28.57%; The proportion of NK cell reduction was 34.31% and 47.62%; The detection value of IL-6 was 0 in 55.88% of the mild group, mild group has a significantly lower proportion of patients with IL-6 higher than normal than severe group; There was no significant linear correlation between the lymphocyte subsets and cytokines, while significant differences were noticed between the two groups in CD4 + T, CD8 + T, IL-6 and IL-10. Conclusions: Low levels of CD4+T and CD8+T are common in severe NCP. IL-6 and IL-10 levels were higher in severe patients. T cell subsets and cytokines can be used as one of the basis for predicting the transition from mild to severe. Large number of samples are still needed to confirm the "warning value" of CD4 + T, CD8 + T IL-6 and IL-10.
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Background Despite limited and conflicting evidence, hydroxychloroquine, alone or in combination with azithromycin, is widely used in COVID-19 therapy. Methods We performed a retrospective study of electronic health records of patients hospitalized with confirmed SARS-CoV-2 infection in United States Veterans Health Administration medical centers between March 9, 2020 and April 29, 2020. Patients hospitalized within 24 hours of diagnosis were classified based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) or no HC as treatments. The primary outcomes were mortality and use of mechanical ventilation. Findings A total of 807 patients were evaluated. Compared to the no HC group, after propensity score adjustment for clinical characteristics, the risk of death from any cause was higher in the HC group (adjusted hazard ratio (aHR), 1.83; 95% CI, 1.16 to 2.89; P=0.009) but not in the HC+AZ group (aHR, 1.31; 95% CI, 0.80 to 2.15; P=0.28). Both the propensity score-adjusted risks of mechanical ventilation and death after mechanical ventilation were not significantly different in the HC group (aHR, 1.19; 95% CI, 0.78 to 1.82; P=0.42 and aHR, 2.11; 95% CI, 0.96 to 4.62; P=0.06, respectively) or in the HC+AZ group (aHR, 1.09; 95% CI, 0.72 to 1.66; P=0.69 and aHR, 1.25; 95% CI, 0.59 to 2.68; P=0.56, respectively), compared to the no HC group. Conclusions Among patients hospitalized with COVID-19, this retrospective study did not identify any significant reduction in mortality or in the need for mechanical ventilation with hydroxychloroquine treatment with or without azithromycin. Funding University of Virginia Strategic Investment Fund.
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The ongoing wreaking global outbreak of the novel human beta coronavirus (CoV) pathogen was presumed to be from a seafood wholesale market in Wuhan, China, belongs to the Coronaviridae family in the Nidovirales order. The virus is highly contagious with potential human-human transmission which was named as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread across six continents and emerged as a global pandemic in short span with alarming levels of spread and severity. This virus associated symptoms and infectious respiratory illness is designated as coronavirus disease 19 (COVID-19). The SARS-CoV-2 possesses enveloped club-like spike protein projections with positive-sense large RNA genome and has a unique replication strategy. This virus was believed to have zoonotic origin with genetical identity to bat and pangolin CoV. In the current review, we introduce a general overview about the human CoVs and the associated diseases, the origin, structure, replication and key clinical events that occur in the COVID-19 pathogenicity. Furthermore, we focused on possible therapeutic options such as repurposing drugs including antimalarials, antivirals, antiparasitic drugs, and anti-HIV drugs, as well as monoclonal antibodies, vaccines as potential treatment options. Also we have summarized the latest research progress on the usage of stem cell therapy, human convalescent serum, interferon's, in the treatment of COVID-19.
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Background The recent emergence of COVID‐19 pandemic has reassessed the usefulness of historic convalescent plasma transfusion (CPT). This review was conducted to evaluate the effectiveness of CPT therapy in COVID‐19 patients based on the publications reported till date. To our knowledge, this is the first systematic review on convalescent plasma on clinically relevant outcomes in individuals with COVID‐19. Methods PubMed, EMBASE and Medline databases were searched upto 19 April 2020. All records were screened as per the protocol eligibility criteria. Results We included 5 studies reporting CPT to COVID‐19 patients. The main findings from available data are as follows: (1) Convalescent plasma may reduce mortality in critically ill patients (2) Increase in neutralizing antibody titers and disappearance of SARS‐CoV‐2 RNA was observed in almost all the patients after CPT therapy (3) Beneficial effect on clinical symptoms after administration of convalescent plasma. Conclusions Based on the limited scientific data, CPT therapy in COVID‐19 patient appears safe, clinically effective and reduces mortality. Well‐designed large multi center clinical trial studies should be conducted urgently to establish the efficacy of CPT to COVID‐19 patients. This article is protected by copyright. All rights reserved.
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Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.