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COVID-19 is the most devastating disease in recent times affecting most people globally. The higher rate of transmissibility and mutations of SARS-CoV-2 along with the lack of potential therapeutics has made it a global crisis. Potential molecules from natural sources could be a fruitful remedy to combat COVID-19. This systematic review highlights the detailed therapeutic implication of naturally occurring glycyrrhizin and its related derivatives against COVID-19. Glycyrrhizin has already been established for blocking different biomolecular targets related to the SARS-CoV-2 replication cycle. In this article, several experimental and theoretical evidences of glycyrrhizin and related derivatives have been discussed in detail to evaluate their potential as a promising therapeutic strategy against COVID-19. Moreover, the implication of glycyrrhizin in traditional Chinese medicines for alleviating the symptoms of COVID-19 has been reviewed. The potential role of glycyrrhizin and related compounds in affecting various stages of the SARS-CoV-2 life cycle has also been discussed in detail. Derivatization of glycyrrhizin for designing potential lead compounds along with combination therapy with other anti-SARS-CoV-2 agents followed by extensive evaluation may assist in the formulation of novel anti-coronaviral therapy for better treatment to combat COVID-19., Competing Interests: The authors declare that there is no conflict of interest., (© 2022 Elsevier B.V. All rights reserved.)

At the end of 2019, Wuhan, China, experienced an outbreak of a novel coronavirus. The SARS-CoV2 epidemiologic burden was constantly evolving, with numbers of infected persons, hospital admissions and deaths growing near exponentially. The pandemic outbreak of COVID-19 worldwide caught the health care systems in every country by storm and without a proper defense mechanism to cope and control such a pandemic, causing an overwhelming burden of illnesses that stressed the Health System capacity. In this context, telemedicine has been promoted and scaled up to reduce the risk of transmission. During the "lockdown", the AOU "Federico II" was forced to create peculiar pathways to ensure the safety of the patients and medical staff, and to keep an appropriate medical assistance, therefore it was introduced the telemedicine, wherever possible, by modifying the Information Technology (IT) related to the waiting times, rescheduling all booked visits and identifying several outpatient clinics suitable for telemedicine activities. In this paper the Authors reports their own experience with Telemedicine., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Inc. All rights reserved.)

With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: In the early stage of the coronavirus disease 2019 (COVID-19) epidemic, small- and mid-sized enterprises (SMEs) may be an important transmission consideration. The study aimed to identify the pattern of COVID-19 prevention measures during the outbreaks in Daegu and Gyeongsangbuk-do at the early stage of COVID-19. Moreover, we investigated whether SME size and past experiences affected the preventive measures implemented in the region., Methods: A survey detailing the general characteristics and implementation of 12 preventive activities was conducted in 122 SMEs in Daegu and Gyeongsangbuk-do. The survey was analyzed by size and operation period., Results: The study subjects consisted of 53 (43.4%) workplaces with 1-5 employees, 50 (40.9%) workplaces with 6-30 employees, and 19 (15.6%) workplaces with 31-49 employees. The lowest three items among those surveyed were 'symptomatic workers to stay home for 3-4 days' (17.2%), 'work remotely' (18.9%), and 'video meetings' (20.5%). There were significant differences in the rate of several preventive measures implemented. The larger sized SMEs, the higher the number of implementations (p < 0.01). The operation period had no significant relationship with the implementation of preventive measures. The same pattern was observed in multiple generalized linear regression with covariate adjustment., Conclusion: Preventive measures among SMEs with fewer than 50 employees were identified. Even within SMEs, a gap in preventive measures according to size was confirmed. To prevent the spread of infection and protect workers' right to health, different support for different sized SMEs is necessary., Competing Interests: All authors declare that they have no conflicts of interest relevant to the content of this literature., (© 2022 Occupational Safety and Health Research Institute.)

Background: COVID-19, which is caused by the corona virus 2 that causes severe acute respiratory syndrome, causes a respiratory and systemic illness that in 10-15% of patients escalates to a severe form of pneumonia. Thrombocytopenia is frequent in patients with COVID-19. We aimed to evaluate the association between thrombocytopenia and the severity of COVID-19 infection in hospitalized patients., Methods: A cross-sectional study was done on 800 Egyptian patients with confirmed covid-19 infection. They were divided into Group I (Mild): 200 symptomatic patients meeting the case definition for COVID-19 without radiological evidence of pneumonia or hypoxia. Group II (Moderate): 200 patients with clinical signs of non-severe pneumonia and radiological evidence of pneumonia. Group III (Severe): 200 patients with clinical signs of pneumonia plus: respiratory or lung dysfunction. Group IV: 200 critically ill patient in ICU: Acute respiratory distress syndrome (ARDS).Results: there was a highly statistically significant difference between the studied groups regarding thrombocytopenia (p < 0.001). Thrombocytopenia was statistically higher in severe and critically ill patients. In addition, a statistically significant difference found in outcome among the studied groups (p < 0.05) {critically ill (40%), severe (17.5%)}. The most common cause of death was respiratory failure, which occurred in 28 severe patients (80%) and 65 critically ill patients (81.25%), followed by hemorrhage due to thrombocytopenia, which occurred in 7 severe patients (20%) and 15 critically ill patients, respectively (18.75%)., Conclusion: The Platelet count is a straightforward, inexpensive, as well as easily available laboratory parameter that is frequently linked to severe covid-19 infection and a significant death risk., Competing Interests: No conflict of interest., (© 2022 The Authors.)

Background: The long-term prognosis of COVID-19 survivors remains poorly understood. It is evidenced that the lung is the main damaged organ in COVID-19 survivors, most notably in impairment of pulmonary diffusion function. Hence, we conducted a meta-analysis of the potential risk factors for impaired diffusing capacity for carbon monoxide (DLCO) in convalescent COVID-19 patients., Methods: We performed a systematic search of PubMed, Web of Science, Embase, and Ovid databases for relevant studies from inception until January 7, 2022, limited to papers involving human subjects. Studies were reviewed for methodological quality. Fix-effects and random-effects models were used to pool results. Heterogeneity was assessed using I 2 . The publication bias was assessed using the Egger's test. PROSPERO registration: CRD42021265377., Findings: A total of eighteen qualified articles were identified and included in the systematic review, and twelve studies were included in the meta-analysis. Our results showed that female (OR: 4.011; 95% CI: 2.928-5.495), altered chest computerized tomography (CT) (OR: 3.002; 95% CI: 1.319-6.835), age (OR: 1.018; 95% CI: 1.007-1.030), higher D-dimer levels (OR: 1.012; 95% CI: 1.001-1.023) and urea nitrogen (OR: 1.004;95% CI: 1.002-1.007) were identified as risk factors for impaired DLCO., Interpretation: Pulmonary diffusion capacity was the most common impaired lung function in recovered patients with COVID-19. Several risk factors, such as female, altered chest CT, older age, higher D-dimer levels and urea nitrogen are associated with impairment of DLCO. Raising awareness and implementing interventions for possible modifiable risk factors may be valuable for pulmonary rehabilitation., Funding: This work was financially supported by Emergency Key Program of Guangzhou Laboratory (EKPG21-29, EKPG21-31), Incubation Program of National Science Foundation for Distinguished Young Scholars by Guangzhou Medical University (GMU2020-207)., Competing Interests: All authors declare that they have no conflict of interest., (© 2022 The Author(s).)

The novel coronavirus disease 2019 (COVID-19) is one of the biggest public health crises globally. Although Africa did not display the worst-case scenario compared to other continents, fears were still at its peak since Africa was already suffering from a heavy load of other life-threatening infectious diseases such as HIV/AIDS and malaria. Other factors that were anticipated to complicate Africa's outcomes include the lack of resources for diagnosis and contact tracing along with the low capacity of specialized management facilities per capita . The current review aims at assessing and generating discussions on the realities, and pros and cons of the WHO COVID-19 interim guidance 2020.5 considering the known peculiarities of the African continent. A comprehensive evaluation was done for COVID-19-related data published across PubMed and Google Scholar (date of the last search: August 17, 2020) with emphasis on clinical management and psychosocial aspects. Predefined filters were then applied in data screening as detailed in the methods. Specifically, we interrogated the WHO 2020.5 guideline viz-a-viz health priority and health financing in Africa, COVID-19 case contact tracing and risk assessment, clinical management of COVID-19 cases as well as strategies for tackling stigmatization and psychosocial challenges encountered by COVID-19 survivors. The outcomes of this work provide links between these vital sub-themes which may impact the containment and management of COVID-19 cases in Africa in the long-term. The chief recommendation of the current study is the necessity of prudent filtration of the global findings along with regional modelling of the global care guidelines for acting properly in response to this health threat on the regional level without exposing our populations to further unnecessary adversities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The outbreak of the COVID-19 pandemic has cost five million lives to date, and was caused by a positive-sense RNA virus named SARS-CoV2. The lack of drugs specific to SARS-CoV2, leads us to search for an effective and specific therapeutic approach. Small interfering RNA (siRNA) is able to activate the RNA interference (RNAi) pathway to silence the specific targeted gene and inhibit the viral replication, and it has not yet attracted enough attention as a SARS-CoV2 antiviral agent. It could be a potential weapon to combat this pandemic until the completion of full scale, effective mass vaccination. For this study, specific siRNAs were designed using a web-based bioinformatics tool (siDirect2.0) against 14 target sequences. These might have a high probability of silencing the essential proteins of SARS-CoV2. such as: 3CLpro/Mpro/nsp5, nsp7, Rd-Rp/nsp12, ZD, NTPase/HEL or nsp13, PLpro/nsp3, envelope protein (E), spike glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), ORF8, ORF3a, nsp2, and its respective 5' and 3'-UTR. Among these potential drug targets, the majority of them contain highly conserved sequences; the rest are chosen on the basis of their role in viral replication and survival. The traditional vaccine development technology using SARS-CoV2 protein takes 6-8 months; meanwhile the virus undergoes several mutations in the candidate protein chosen for vaccine development. By the time the protein-based vaccine reaches the market, the virus would have undergone several mutations, such that the antibodies against the viral sequence may not be effective in restricting the newly mutated viruses. However, siRNA technology can make sequences based on real time viral mutation status. This has the potential for suppressing SARS-CoV2 viral replication, through RNAi technology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Inc. All rights reserved.)

Diabetes mellitus is a metabolic disease that causes hyperglycemia. In COVID-19 patients the severity of the disease depends on myriad factors but diabetes mellitus is the most important comorbidity. The current review was conducted to investigate the virulence of SARS-CoV-2 and disease severity of COVID-19 in type 2 diabetes mellitus patients and relevant treatment. The literature published in PubMed, Scopus, Web of Science, and Google Scholar was reviewed up to September 2021. The keywords including SARS-CoV-2, type 2 diabetes mellitus in COVID-19, hyperglycemia in COVID-19, opportunistic infections in type 2 diabetes mellitus and COVID-19 were used in different combinations. Hyperglycemic individuals over-express ACE-2 receptors in the lungs thus increasing the SARS-CoV-2 susceptibility and replication. Although dipeptidyl peptidase-4 plays an important role in glucose homeostasis, additionally it also stimulates the production of proinflammatory cytokines such as IL-6 and TNF-α creating a cytokine storm. Cytokine storm might be responsible for respiratory insufficiency in severe COVID-19 patients. Type 2 diabetes mellitus is associated with immunosuppression and the patients are prone to get many opportunistic infections. Type 2 diabetes mellitus patients with severe COVID-19 have lymphopenia. Moreover, in type 2 diabetes mellitus patients the neutrophils exhibit decreased chemotaxis, hydrogen peroxide production, and phagocytosis. Reduction in lymphocyte count and defective neutrophil capacity renders them with COVID-19 susceptible to opportunistic bacterial and fungal infections increasing the mortality rate. The opportunistic bacterial infections in COVID-19 patients were due to Staphylococcus aureus , Streptococcus pneumonia, and coagulase-negative Staphylococci, E . coli , Pseudomonas aeruginosa , and Klebsiella sp. In COVID-19 patients with type 2 diabetes mellitus, mucormycosis was found to be the most common fungal infection with a higher predilection to males. Hyperglycemia in COVID-19 patients with type 2 diabetes mellitus enhances the SARS-CoV-2 replication with an adverse outcome. A strong correlation exists between the poor prognosis of COVID-19 and type 2 diabetes mellitus. Proper glycemic control in COVID-19 patients with diabetes mellitus might lessen the severity of the disease., Competing Interests: The authors declare no conflict of interests., (© 2022 Elsevier Inc. All rights reserved.)

As the world has been facing several deadly virus crises, including Zika virus disease, Ebola virus disease, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Coronavirus disease 2019 (COVID-19), lateral flow assays (LFAs), which require minimal equipment for point-of-care of viral infectious diseases, are garnering much attention. Accordingly, there is an increasing demand to reduce the time and cost required for manufacturing LFAs. The current study introduces an equipment-free method of sa lt-mediated i mmobilization o f n ucleic acid s (SAIoNs) for LFAs. Compared to general DNA immobilization methods such as streptavidin-biotin, UV-irradiation, and heat treatment, our method does not require special equipment (e.g., centrifuge, UV-crosslinker, heating device); therefore, it can be applied in a resource-limited environment with reduced production costs. The immobilization process was streamlined and completed within 30 min. Our method improved the color intensity signal approximately 14 times compared to the method without using SAIoNs and exhibited reproducibility with the long-term storage stability. The proposed method can be used to detect practical targets (e.g., SARS-CoV-2) and facilitates highly sensitive and selective detection of target nucleic acids with multiplexing capability and without any cross-reactivity. This novel immobilization strategy provides a basis for easily and inexpensively developing nucleic acid LFAs combined with various types of nucleic acid amplification., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier B.V. All rights reserved.)

The COVID-19 pandemic and its resulting containment measures have forced many children and their caregivers around the world to spend unprecedented amounts of time at home. Based on a sample of 764 households with preschool-aged children in Wuhan, China, where the pandemic began, this study examined how primary caregivers perceived changes in the amount of time spent engaging with their children (i.e., engaged time) from the start of the pandemic and whether these changes were associated with children's learning behavior and emotional distress. The results showed that primary caregivers generally perceived increases in the amount of engaged time spent on indoor activities with their children but decreases in the amount of engaged time spent playing with their children outdoors. A bigger family size and greater loss of family income during the pandemic were associated with bigger perceived increases in caregivers' engaged time spent on indoor activities, whilst a higher level of parental education was associated with bigger perceived decreases in engaged time spent playing with children outdoors. The family's poorer physical health and higher levels of chaos during the pandemic were related to smaller perceived increases in caregivers' engaged time spent on educational activities. Finally, although bigger perceived increases in caregivers' indoor engaged time (e.g., time spent on educational activities) were associated with higher levels of positive learning behavior and fewer symptoms of anxiety and withdrawal in the children, bigger perceived decreases in outdoor play time were associated with fewer symptoms of anxiety and withdrawal. These findings offer valuable insights into caregivers' allocation of engaged time with their preschool-aged children during the COVID-19 pandemic., (© 2022 Elsevier Inc. All rights reserved.)

Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS), molecular docking (MD) then molecular dynamic simulation (MDS) analysis and MMGBSA calculations. The QSAR-based virtual screening was utilized to find novel lead molecules from an in-house database of 100 molecules. The QSAR-vS successfully offered a hit molecule with an improved P EC 50 value from 5.88 to 6.08. The benzene ring, phenyl ring, amide oxygen and nitrogen, and other important pharmacophoric sites are revealed via MD and MDS studies. Ile164, Pro188, Leu190, Thr25, His41, Asn46, Thr47, Ser49, Asn189, Gln191, Thr47, and Asn141 are among the key amino acid residues in the S1 and S2 pocket. A stable complex of a lead molecule with the HCoV SARS 3CLpro was discovered using MDS. MM-GBSA calculations resulted from MD simulation results well supported with the binding energies calculated from the docking results. The results of this study can be exploited to develop a novel antiviral target, such as an HCoV SARS 3CLpro Inhibitor., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The SARS-CoV-2 spike protein is the first contact point between the SARS-CoV-2 virus and host cells and mediates membrane fusion. Recently, a fatty acid binding site was identified in the spike (Toelzer et al. Science 2020). The presence of linoleic acid at this site modulates binding of the spike to the human ACE2 receptor, stabilizing a locked conformation of the protein. Here, dynamical-nonequilibrium molecular dynamics simulations reveal that this fatty acid site is coupled to functionally relevant regions of the spike, some of them far from the fatty acid binding pocket. Removal of a ligand from the fatty acid binding site significantly affects the dynamics of distant, functionally important regions of the spike, including the receptor-binding motif, furin cleavage site and fusion-peptide-adjacent regions. Simulations of the D614G mutant show differences in behaviour between these clinical variants of the spike: the D614G mutant shows a significantly different conformational response for some structural motifs relevant for binding and fusion. The simulations identify structural networks through which changes at the fatty acid binding site are transmitted within the protein. These communication networks significantly involve positions that are prone to mutation, indicating that observed genetic variation in the spike may alter its response to linoleate binding and associated allosteric communication., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Africa is endowed with a profoundly rich and diverse system of plants and other bio-resources out of which, by traditional medicine practice, the people have satisfied their healthcare needs right from antiquity. In contemporary times, it has become necessary to modernize this traditional medical care system via scientific studies. Validation of the efficacy of health-enhancement products and drugs from plants and other bio-resources is predicated on diligent and intensive research accompanied by rigorous and conclusive clinical trials. Africa has eminently qualified human resources but due to the finance-intensive nature of medical research, individual African states on their own cannot fund the level of research desired for dealing with such serious issues as the COVID-19 pandemic. A collaboration among African states guided by a Mutual Pan-African support paradigm (MPASP) is a unique strategy for achieving success in any such a high-impact global project as the use of traditional medicine against COVID-19 and emerging pandemics; and this is hereby advocated., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V. on behalf of African Institute of Mathematical Sciences / Next Einstein Initiative.)

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Virus-induced infection such as SARS-CoV-2 is a serious threat to human health and the economic setback of the world. Continued advances in the development of technologies are required before the viruses undergo mutation. The low concentration of viruses in environmental samples makes the detection extremely challenging; simple, accurate and rapid detection methods are in urgent need. Of all the analytical techniques, electrochemical methods have the established capabilities to address the issues. Particularly, the integration of nanotechnology would allow miniature devices to be made available at the point-of-care. This review outlines the capabilities of electrochemical methods in conjunction with nanotechnology for the detection of SARS-CoV-2. Future directions and challenges of the electrochemical biosensors for pathogen detection are covered including wearable and conformal biosensors, detection of plant pathogens, multiplexed detection, and reusable biosensors for on-site monitoring, thereby providing low-cost and disposable biosensors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier B.V. All rights reserved.)

SARS-CoV-2 virus, the main culprit for COVID-19 disaster, has triggered a gust of curiosity both in the mechanism of action of this infection as well as potential risk factors for disease generation and regimentation. The prime focus of the present review, which is basically a narrative one, is in utilizing the current concepts of vitamin D 3 as an agent with myriad functions, one of them being immunocompetence and a promising weapon for both innate and adaptive immunity against COVID-19 infection. Some of the manifestations of SARS-CoV-2 virus such as Acute Respiratory Distress Syndrome (ARDS) overlap with the pathophysiological effects that are overcome due to already established role of vitamin D 3 e.g., amelioration of cytokine outburst. Additionally, the cardiovascular complications due to COVID-19 infection may also be connected to vitamin D 3 levels and the activity of its active forms. Eventually, we summarise the clinical, observational and epidemiological data of the respiratory diseases including COVID-19 disease and try to bring its association with the potential role of vitamin D 3 , in particular, the activity of its active forms, circulating levels and its supplementation, against dissemination of this disease., Competing Interests: The authors confirm that this article content has no conflicts of interest., (© 2021 Elsevier Inc. All rights reserved.)

Background: Several recent studies have stated that glycyrrhizin and licorice extract are present in most traditional Chinese medicine formulas used against SARS-CoV-2 in China. Significant data are showing that glycyrrhizin and licorice extract have multiple beneficial activities in combating most features of SARS-CoV-2., Purpose: The aim of current review was to highlight recent progresses in research that showed the evidence of the potential use of glycyrrhizin and licorice extract against COVID-19., Methodology: We have reviewed the information published from 1979 to October 2020. These studies demonstrated the effects , use and safety of glycyrrhizin and icorice extract against viral infections,bacterial infections, inflammatory disorders of lung ( in vitro and in vivo).  These studies were collated through online electronic databases research (Academic libraries as PubMed, Scopus, Web of Science and Egyptian Knowledge Bank)., Results: Pooled effect size of articles provides information about the rationale for using glycyrrhizin and licorice extract to treat COVID-19. Fifty studies demonstrate antiviral activity of glycyrrhizin and licorice extract. The most frequent mechanism of the antiviral activity is due to disrupting viral uptake into the host cells and disrupting the interaction between receptor- binding domain (RBD) of SARS-COV2 and ACE2 in recent articles. Fifty studies indicate that glycyrrhizin and licorice extract have significant antioxidant, anti-inflammatory and immunomodulatory effects. Twenty five studies provide evidence for the protective effect of glycyrrhizin and licorice extract against inflammation-induced acute lung injury and cardiovascular disorders., Conclusion: The current study showed several evidence regarding the beneficial effects of glycyrrhizin and licorice extract in combating COVID-19. More randomized clinical trials are needed to obtain a precise conclusion., Competing Interests: All authors declare that they have no conflict of interest., (© 2021 The Author(s).)

The first known case of Coronavirus disease 2019 (COVID-19) was identified in December 2019. It has spread worldwide, leading to an ongoing pandemic, imposed restrictions and costs to many countries. Predicting the number of new cases and deaths during this period can be a useful step in predicting the costs and facilities required in the future. The purpose of this study is to predict new cases and deaths rate one, three and seven-day ahead during the next 100 days. The motivation for predicting every n days (instead of just every day) is the investigation of the possibility of computational cost reduction and still achieving reasonable performance. Such a scenario may be encountered in real-time forecasting of time series. Six different deep learning methods are examined on the data adopted from the WHO website. Three methods are LSTM, Convolutional LSTM, and GRU. The bidirectional extension is then considered for each method to forecast the rate of new cases and new deaths in Australia and Iran countries. This study is novel as it carries out a comprehensive evaluation of the aforementioned three deep learning methods and their bidirectional extensions to perform prediction on COVID-19 new cases and new death rate time series. To the best of our knowledge, this is the first time that Bi-GRU and Bi-Conv-LSTM models are used for prediction on COVID-19 new cases and new deaths time series. The evaluation of the methods is presented in the form of graphs and Friedman statistical test. The results show that the bidirectional models have lower errors than other models. A several error evaluation metrics are presented to compare all models, and finally, the superiority of bidirectional methods is determined. This research could be useful for organisations working against COVID-19 and determining their long-term plans., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

The fast spread of SARS-CoV-2 presented a worldwide challenge to public health, economy, and educational system, affecting wellbeing of human society. With high transmission rates, there are increasing evidences of COVID-19 spread via bioaerosols from an infected person. The current review was conducted to examine airborne pollen impact on COVID-19 transmission and to identify the major gaps for post-pandemic research. The study used all key terms to identify revenant literature and observation were collated for the current research. Based on existing literature, there is a potential association between pollen bioaerosols and COVID-19. There are few studies focusing the impact of airborne pollen on SARS-CoV-2, which could be useful to advance future research. Allergic rhinitis and asthma patients were found to have pre-modified immune activation, which could help to provide protection against COVID-19. However, does airborne pollen acts as a potent carrier for SARS-CoV-2 transport, dispersal and its proliferation still require multidisciplinary research. Further, a clear conclusion cannot be drawn due to limited evidence and hence more research is needed to show how pollen bioaerosols could affect virus survivals. The small but growing literature review focuses on searching for every possible answer to provide additional security layers to overcome near future corona-like infectious diseases., Competing Interests: The authors report no declarations of interest., (© 2021 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to distinguish the imaging features of COVID-19 from those of other infectious pulmonary diseases and evaluate the diagnostic value of chest CT for suspected COVID-19 patients., Methods: Adult patients suspected of COVID-19 aged >18 years who underwent chest CT scans and reverse-transcription polymerase chain reaction (RT-PCR) tests within 14 days of symptom onset were enrolled. The enrolled patients were confirmed and grouped according to the results of the RT-PCR tests. The basic demographics, single chest CT features, and combined chest CT features were analyzed for the confirmed and nonconfirmed groups., Results: A total of 130 patients were enrolled, with 54 testing positive and 76 testing negative. The typical CT imaging features of the positive group were ground glass opacities (GGOs), the crazy-paving pattern and air bronchogram. The lesions were mostly distributed bilaterally and close to the lower lungs or the pleura. When features were combined, GGOs with bilateral pulmonary distribution and GGOs with pleural distribution were more common among the positive patients, found in 31 (57.4%) and 30 patients (55.6%), respectively. The combinations were almost all statistically significant ( P  < .05), except for the combination of GGOs with consolidation. Most combinations presented relatively low sensitivity but extremely high specificity. The average specificity of these combinations was approximately 90%., Conclusions: The combinations with GGOs could be useful in the identification and differential diagnosis of COVID-19, alerting clinicians to isolate patients for prompt treatment and repeat RT-PCR tests until the end of incubation., (© 2020 Elsevier Inc. All rights reserved.)

In late 2019, a novel Coronavirus emerged in China. Perceiving the modulating factors of cross-species virus transmission is critical to elucidate the nature of virus emergence. Using bioinformatics tools, we analyzed the mapping of the SARS-CoV-2 genome, modeling of protein structure, and analyze the evolutionary origin of SARS-CoV-2, as well as potential recombination events. Phylogenetic tree analysis shows that SARS-CoV-2 has the closest evolutionary relationship with Bat-SL-CoV-2 (RaTG13) at the scale of the complete virus genome, and less similarity to Pangolin-CoV. However, the Receptor Binding Domain (RBD) of SARS-CoV-2 is almost identical to Pangolin-CoV at the aa level, suggesting that spillover transmission probably occurred directly from pangolins, but not bats. Further recombination analysis revealed the pathway for spillover transmission from Bat-SL-CoV-2 and Pangolin-CoV. Here, we provide evidence for recombination event between Bat-SL-CoV-2 and Pangolin-CoV that resulted in the emergence of SARS-CoV-2. Nevertheless, the role of mutations should be noted as another influencing factor in the continuing evolution and resurgence of novel SARS-CoV-2 variants., Competing Interests: No conflict of interests to declare., (© 2021 Elsevier Inc. All rights reserved.)

The novel corona virus disease or COVID-19 caused by a positive strand RNA virus (PRV) called SARS-CoV-2 is plaguing the entire planet as we conduct this study. In this study a multifaceted analysis was carried out employing dinucleotide signature, codon usage and codon context to compare and unravel the genomic as well as genic characteristics of the SARS-CoV-2 isolates and how they compare to other PRVs which represents some of the most pathogenic human viruses. The main emphasis of this study was to comprehend the codon biology of the SARS-CoV-2 in the backdrop of the other PRVs like Poliovirus, Japanese encephalitis virus, Hepatitis C virus, Norovirus , Rubella virus, Semliki Forest virus, Zika virus, Dengue virus, Human rhinoviruses and the Betacoronaviruses since codon usage pattern along with the nucleotide composition prevalent within the viral genome helps to understand the biology and evolution of viruses. Our results suggest discrete genomic dinucleotide signature within the PRVs. Some of the genes from the different SARS-CoV-2 isolates were also found to demonstrate heterogeneity in terms of their dinucleotide signature. The SARS-CoV-2 isolates also demonstrated a codon context trend characteristically dissimilar to the other PRVs. The findings of this study are expected to contribute to the developing global knowledge base in countering COVID-19., Competing Interests: All the authors declare that they have no conflict of interest., (© 2021 Elsevier Inc. All rights reserved.)

COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 International Hemorrhagic Stroke Association. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Post-Acute COVID-19 Syndrome (PACS) is defined by persistent symptoms >3-4 weeks after onset of COVID-19. The mechanism of these persistent symptoms is distinct from acute COVID-19 although not completely understood despite the high incidence of PACS. Cardiovascular symptoms such as chest pain and palpitations commonly occur in PACS, but the underlying cause of symptoms is infrequently known. While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. Additionally, patients hospitalized with acute COVID-19 who display biomarker evidence of myocardial injury may have underlying coronary artery disease revealed by the physiological stress of SARS-CoV-2 infection and may benefit from medical optimization. We review what is known about PACS and the cardiovascular system and propose a framework for evaluation and management of related symptoms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: In December 2019, a novel coronavirus, SARS-CoV-2 caused a series of acute atypical respiratory diseases worldwide. However, there is still a lack of drugs with clear curative effects, and the clinical trial research of vaccines has not been completely finished., Purpose: LH capsules are approved TCM patent medicine that are widely used for the treatment of respiratory tract infectious diseases caused by colds and flu. On April 12, 2020, LH capsules and granules were officially repurposed by the China Food and Drug Administration (CFDA) for patients with mild COVID-19 based on their safety and efficacy demonstrated through multicentre, randomized, controlled clinical trials. We hope to conduct a comprehensive review of it through modern pharmacy methods, and try to explain its possible mechanism., Methods: Using the full names of LH capsules Lianhuaqingwen, Lianhua Qingwen andSARS-COV-2, COVID-19 as the keywords of the search terms, systemically search for existing related papers in various databases such as Web of Science and PubMed. And completed the collection of clinical data in ClinicalTrials.gov and Chinese Clinical Trial Registry. Last but not least, we have sorted out the anti-inflammatory and antiviral mechanisms of LH capsules through literature and Selleck., Results: This review systematically sorted out the active ingredients in LH capsules. Furthermore, the related pharmacological and clinical trials of LH capsule on SARS-CoV-2, IAV and IBV were discussed in detail. Moreover, the present review provides the first summary of the potential molecular mechanism of specific substances in LH capsules involved in resistance to SARS-COV-2 infection and the inhibition of cytokine storm syndrome (CSS) caused by IL-6., Conclusion: This review summarizes the available reports and evidence that support the use of LH capsules as potential drug candidates for the prevention and treatment of COVID-19. However, TCM exerts its effects through multiple targets and multiple pathways, and LH capsules are not an exception. Therefore, the relevant mechanisms need to be further improved and experimentally verified., Competing Interests: We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (© 2021 The Authors. Published by Elsevier B.V.)

Background: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19)., Methods: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate ( n  = 17), severe ( n  = 40) and critical groups ( n  = 43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve., Results: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 μg/L vs. 501.90 μg/L, p  < 0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p  = 0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP., Conclusion: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU., (© 2020 Elsevier España, S.L.U. All rights reserved.)

Viruses are biologically active parasites that only exist inside a host they are submicroscopic level. The novel coronavirus disease, or COVID-19, is generally caused by the SARS-CoV-2 virus and is comparable to severe acute respiratory syndrome (SARS). As a result of globalization, natural alterations or changes in the SARS-CoV-2 have created significant risks to human health over time. These viruses can live and survive in different ways in the atmosphere unless they reach another host body. At this stage, we will discuss the details of the transmission and detection of this deadly SARS-CoV-2 virus via certain environmental media, such as the atmosphere, water, air, sewage water, soil, temperature, relative humidity, and bioaerosol, to better understand the diffusion, survival, infection potential and diagnosis of COVID-19., Competing Interests: The authors declare that they have no competing interests., (© 2021 Published by Elsevier B.V.)

Introduction: Patients with pre-existing respiratory diseases in the setting of COVID-19 may have a greater risk of severe complications and even death., Methods: A retrospective, multicenter, cohort study with 5847 COVID-19 patients admitted to hospitals. Patients were separated in two groups, with/without previous lung disease. Evaluation of factors associated with survival and secondary composite end-point such as ICU admission and respiratory support, were explored., Results: 1,271 patients (22%) had a previous lung disease, mostly COPD. All-cause mortality occurred in 376 patients with lung disease (29.5%) and in 819 patients without (17.9%) ( p  < 0.001). Kaplan-Meier curves showed that patients with lung diseases had a worse 30-day survival (HR = 1.78; 95%C.I. 1.58-2.01; p  < 0.001) and COPD had almost 40% mortality. Multivariable Cox regression showed that prior lung disease remained a risk factor for mortality (HR, 1.21; 95%C.I. 1.02-1.44; p  = 0.02). Variables independently associated with all-cause mortality risk in patients with lung diseases were oxygen saturation less than 92% on admission (HR, 4.35; 95% CI 3.08-6.15) and elevated D-dimer (HR, 1.84; 95% CI 1.27-2.67). Age younger than 60 years (HR 0.37; 95% CI 0.21-0.65) was associated with decreased risk of death., Conclusions: Previous lung disease is a risk factor for mortality in patients with COVID-19. Older age, male gender, home oxygen therapy, and respiratory failure on admission were associated with an increased mortality. Efforts must be done to identify respiratory patients to set measures to improve their clinical outcomes., (© 2020 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

In the modern global context of interconnected populations, the recent emergence of infectious diseases involves complex interactions. The purpose of this study is to investigate the spatial correlations between urban characteristics, taking into account the socio-ecological aspects, and the emergence of infectious diseases. Using exploratory spatial data analysis and spatial regression between the infectious disease emergence data and 14 urban characteristics, we analyzed 225 spatial units in South Korea, where there was a re-emergence of measles and a 2015 outbreak of Middle East Respiratory Syndrome. As results of exploratory spatial data analysis, the emerging infectious diseases had spatial dependence and showed spatial clusters. Spatial regression models showed that urban characteristic factors had different effects according to the type of infectious disease. Common factors were characteristics related to low socioeconomic status in water or food-borne diseases and manageable infectious diseases. Intermittent infections disease epidemics are related to high-quality residential environments and the response capacity of the local government. New infectious diseases are different than other infectious diseases, which are related to the ecological environment. This study suggests spatial policies for preventing infectious diseases considering the spatial relationships between urban characteristics and infectious diseases as well as the management of public health., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

SARS-CoV-2 infection was announced as a pandemic in March 2020. Since then, several scientists have focused on the low prevalence of smokers among hospitalized COVID-19 patients. These findings led to our hypothesis that the Nicotinic Cholinergic System (NCS) plays a crucial role in the manifestation of COVID-19 and its severe symptoms. Molecular modeling revealed that the SARS-CoV-2 Spike glycoprotein might bind to nicotinic acetylcholine receptors (nAChRs) through a cryptic epitope homologous to snake toxins, substrates well documented and known for their affinity to the nAChRs. This binding model could provide logical explanations for the acute inflammatory disorder in patients with COVID-19, which may be linked to severe dysregulation of NCS. In this study, we present a series of complexes with cholinergic agonists that can potentially prevent SARS-CoV-2 Spike glycoprotein from binding to nAChRs, avoiding dysregulation of the NCS and moderating the symptoms and clinical manifestations of COVID-19. If our hypothesis is verified by in vitro and in vivo studies, repurposing agents currently approved for smoking cessation and neurological conditions could provide the scientific community with a therapeutic option in severe COVID-19., Competing Interests: The authors report no declarations of interest., (© 2020 The Authors. Published by Elsevier B.V.)

The COVID-19 pandemic has required clinicians to urgently identify new treatment options or the re-purposing of existing drugs. Of particular interest are chloroquine (CQ) and hydroxychloroquine (HCQ). The aims of this systematic review are to systematically identify and collate 24 studies describing the use of CQ and HCQ in human clinical trials and to provide a detailed synthesis of evidence of its efficacy and safety. Of clinical trials, 100% showed no significant difference in the probability of viral transmission or clearance in prophylaxis or therapy, respectively, compared to the control group. Among observational studies employing an endpoint specific to efficacy, 58% concurred with the finding of no significant difference in the attainment of outcomes. Three-fifths of clinical trials and half of observational studies examining an indicator unique to drug safety discovered a higher probability of adverse events in those treated patients suspected of, and diagnosed with, COVID-19. Of the total papers focusing on cardiac side-effects, 44% found a greater incidence of QTc prolongation and/or arrhythmias, 44% found no evidence of a significant difference, and 11% mixed results. The strongest available evidence points towards the inefficacy of CQ and HCQ in prophylaxis or in the treatment of hospitalised COVID-19 patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

The novel severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19), quickly spread around the world, resulting in the most aggressive pandemic experienced in more than 100 years. Research on targeted therapies and vaccines has been initiated on an unprecedented scale and speed but will take months and even years to come to fruition. Meanwhile, the efficacy of emerging therapeutics for use in treating COVID-19 is feverishly being investigated to identify the best available treatment options for dealing with the current wave of disease. This review of publications with a "treatment" tag through June 29, 2020 in the National Library of Medicine's LitCovid literature hub, provides frontline clinicians with a pragmatic summary of the current state of the rapidly evolving evidence supporting emerging candidate therapeutics for COVID-19. Two main categories of pharmaceutical therapeutics are showing promise: those with antiviral activity directly addressing infection and those that counteract the inflammatory cytokine storm induced by severe disease. Preliminary results suggest that other approaches such as convalescent plasma therapy and lung radiation therapy may have some efficacy. The current clinical evidence for potential treatments is preliminary-often small retrospective series or early results of randomized trials-and the science is evolving rapidly. The long-term results from large, well-designed randomized controlled trials will provide definitive evidence for therapeutic effectiveness and are likely months away. The trial landscape for promising therapies is described., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

COVID-19, responsible of infecting billions of people and economy across the globe, requires detailed study of the trend it follows to develop adequate short-term prediction models for forecasting the number of future cases. In this perspective, it is possible to develop strategic planning in the public health system to avoid deaths as well as managing patients. In this paper, proposed forecast models comprising autoregressive integrated moving average (ARIMA), support vector regression (SVR), long shot term memory (LSTM), bidirectional long short term memory (Bi-LSTM) are assessed for time series prediction of confirmed cases, deaths and recoveries in ten major countries affected due to COVID-19. The performance of models is measured by mean absolute error, root mean square error and r2&#95;score indices. In the majority of cases, Bi-LSTM model outperforms in terms of endorsed indices. Models ranking from good performance to the lowest in entire scenarios is Bi-LSTM, LSTM, GRU, SVR and ARIMA. Bi-LSTM generates lowest MAE and RMSE values of 0.0070 and 0.0077, respectively, for deaths in China. The best r2&#95;score value is 0.9997 for recovered cases in China. On the basis of demonstrated robustness and enhanced prediction accuracy, Bi-LSTM can be exploited for pandemic prediction for better planning and management., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and there are obvious concerns for the immunocompromised patient population including transplant recipients. Creating awareness and understanding patient concerns will play an important role in protecting this vulnerable group in developing timely and appropriate healthcare interventions., Methods: A cross-sectional online survey was conducted between 23rd March 2020 and 1st April 2020 among 154 liver transplant recipients, transplanted between October 2018 and February 2020. An 18-point questionnaire explored their knowledge of COVID-19, awareness of recipient's high-risk status, interventions to minimize cross-infections, and concerns of this patient group regarding the pandemic., Results: There were 112 (73%) respondents, with median age of 53 years (81% males). There was no difference in demographics between those who responded (n = 112) and those who did not respond to the survey (n = 42). Most of the recipients were aware of the main symptoms of COVID-19, such as fever (92%), breathlessness (86%), and dry cough (87%), but less than half were aware of diarrhea (39%) as a symptom. Awareness about spread from asymptomatic individuals was limited (26%). Majority (95%) understood their high-risk status, but worryingly, 23% of the respondents felt that there was no risk in visiting the hospital for routine clinic visit and blood tests. Concerns were raised by the recipients mostly regarding the uncertainties of COVID-19 infection and its treatment options, the quality of information on social messaging platforms, and lack of access to routine tests/immunosuppression levels because of lockdown/social distancing., Conclusions: Our liver transplant recipients have a reasonable awareness regarding COVID-19. Problems in accessing the healthcare system during prolonged periods of lockdown was a major concern. It is important for each transplant unit to educate, support, and remain accessible to this vulnerable patient cohort as the pandemic continues to progress worldwide., Competing Interests: The authors have none to declare., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Clinical studies have shown that renal injury in Corona Virus Disease 2019 (COVID-19) patients has been a real concern, which is associated with high mortality and an inflammation/apoptosis-related causality. Effective target therapy for renal injury has yet been developed. Besides, potential anti-COVID-19 medicines have also been reported to cause adverse side effects to kidney. Chinese Herbal Medicine (CHM), however, has rich experience in treating renal injury and has successfully applied in China in the battle of COVID-19. Nevertheless, the molecular mechanisms of CHM treatment are still unclear. In this study, we searched prescriptions in the treatment of renal injury extensively and the potential mechanisms to treat COVID-19 related renal injury were investigated. The association rules analysis showed that the core herbs includes Huang Qi, Fu Ling, Bai Zhu, Di Huang, Shan Yao. TCM herbs regulate core pathways, such as AGE-RAGE, PI3K-AKT, TNF and apoptosis pathway, etc. The ingredients (quercetin, formononetin, kaempferol, etc.,) from core herbs could modulate targets (PTGS2 (COX2), PTGS1 (COX1), IL6, CASP3, NOS2, and TNF, etc.), and thereby prevent the pharmacological and non-pharmacological renal injury comparable to that from COVID-19 infection. This study provides therapeutic potentials of CHM to combat COVID-19 related renal injury to reduce complications and mortality., (© 2020 The Authors.)

Asthma is increasingly recognized as an underlying risk factor for severe respiratory disease in patients with coronavirus disease 2019 (COVID-19), particularly in the United States. Here, we report the postmortem lung findings from a 37-year-old man with asthma, who met the clinical criteria for severe acute respiratory distress syndrome and died of COVID-19 less than 2 weeks after presentation to the hospital. His lungs showed mucus plugging and other histologic changes attributable to asthma, as well as early diffuse alveolar damage and a fibrinous pneumonia. The presence of diffuse alveolar damage is similar to descriptions of autopsy lung findings from patients with severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, and the absence of a neutrophil-rich acute bronchopneumonia differs from the histologic changes typical of influenza. The relative contribution of mucus plugging to his hypoxemia is unknown., (© 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the main neurological manifestations related to coronavirus infection in humans., Methodology: A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: "coronavirus" or "Sars-CoV-2" or "COVID-19" and "neurologic manifestations" or "neurological symptoms" or "meningitis" or "encephalitis" or "encephalopathy," following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11 % and 12 % of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8 %), dizziness (57, 13.9 %), altered consciousness (46; 11.2 %), vomiting (26; 6.3 %), epileptic crises (7; 1.7 %), neuralgia (5; 1.2 %), and ataxia (3; 0.7 %). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1 %) patients, hypoxic encephalopathy in 23 (5.6 %) patients, acute cerebrovascular disease in 6 (1.4 %) patients, 1 (0.2 %) patient with possible acute disseminated encephalomyelitis, 1 (0.2 %) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4 %) patients with CoV related to Guillain-Barré syndrome., Conclusion: Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness., Competing Interests: The authors declare that they have no competing interests., (© 2020 Elsevier GmbH. All rights reserved.)

In February 2020, the exponential growth of COVID-19 cases in Wuhan city posed a huge economic burden to local medical systems. Consequently, Wuhan established Fangcang Shelter hospitals as a One Health approach for responding to and containing the COVID-19 outbreak by isolating and caring for mild-to-moderate cases. However, it is unclear to what degree the hospitals contained COVID-19. This study performed an interrupted time series analysis to compare the number of new confirmed cases of COVID-19 before and after the operation of Fangcang Shelter hospitals. The initial number of confirmed cases in Wuhan increased significantly by 68.54 cases per day prior to February 4, 2020. Compared with the number of cases noted 20 days before the use of Fangcang Shelter hospitals, a sustained reduction in the number of confirmed cases (trend change, -125.57; P  < 0.0001) was noted 41 days after the use of the hospitals. Immediate-level changes were observed for confirmed cases (level change, 725.97; P  = 0.025). These changes led to an estimated 5148 fewer confirmed cases ( P  < 0.0001). According to the mean confirmed cases of 395.71 per day before the intervention, we estimated that Wuhan had advanced the terminal phase of COVID-19 by 13 days. Furthermore, immediately after introduction of Fangcang Shelter Hospitals on February 5, the reproduction number dropped rapidly, from a pre-introduction rate of 4.0 to 2.0. The Fangcang Shelter hospitals most likely to reversed the epidemic trend of COVID-19 while a containment strategy was implemented in Wuhan. In a One Health perspective, Fangcang Shelter hospitals, with their functions of isolation and treatment of confirmed COVID-19 patients, engaging professionals from many disciplines, such as medicine, engineering, architecture, psychology, environmental health, and social sciences. The results of this study provide a valuable reference for health policy makers in other countries., Competing Interests: The authors declare that they have no competing interests., (© 2020 Published by Elsevier B.V.)

The nucleocapsid (N) protein is conserved in all four genera of the coronaviruses, namely alpha, beta, gamma, and delta, and is essential for genome functionality. Bioinformatic analysis of coronaviral N sequences revealed two intrinsically disordered regions (IDRs) at the center of the polypeptide. While both IDR structures were found in alpha, beta, and gamma-coronaviruses, the second IDR was absent in deltacoronaviruses. Two novel coronaviruses, currently placed in the Gammacoronavirus genus, appeared intermediate in this regard, as the second IDR structure could be barely discerned with a low probability of disorder. Interestingly, these two are the only coronaviruses thus far isolated from marine mammals, namely beluga whale and bottlenose dolphin, two highly related species; the N proteins of the viruses were also virtually identical, differing by a single amino acid. These two unique viruses remain phylogenetic oddities, since gammacoronaviruses are generally avian (bird) in nature. Lastly, both IDRs, regardless of the coronavirus genus in which they occurred, were rich in Ser and Arg, in agreement with their disordered structure. It is postulated that the central IDRs make cardinal contributions in the multitasking role of the nucleocapsid protein, likely requiring structural plasticity, perhaps also impinging on coronavirus host tropism and cross-species transmission., (© 2020 The Author(s).)

Coronaviruses (CoVs), a family of enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, unusually large RNA genome, and unique replication capability. CoVs are known to cause various potentially lethal human respiratory infectious diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the very recent coronavirus disease 2019 (COVID-19) outbreak. Unfortunately, neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs. Therefore, effective prevention and treatment medications against human coronavirus are in urgent need. In the past decades, many natural compounds have been reported to possess multiple biological activities, including antiviral properties. In this article, we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS, and discussed their potential use for the treatment of COVID-19., Competing Interests: The authors declare that they have no competing interests., (© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Coronavirus disease-19 (COVID-19) is a viral pandemic that started in China and has rapidly expanded worldwide. Typical clinical manifestations include fever, cough and dyspnea after an incubation period of 2-14 days. The diagnosis is based on RT-PCR test through a nasopharyngeal swab. Because of the pulmonary tropism of the virus, pneumonia is often encountered in symptomatic patients. Here, we review the pertinent clinical findings and the current published data describing chest CT findings in COVID-19 pneumonia, the diagnostic performance of CT for diagnosis, including differential diagnosis, as well the evolving role of imaging in this disease., Competing Interests: There is no conflict of interest associated with this publication and there has been no financial support for this work, (© 2020 The Authors.)

The coronavirus disease-2019 (COVID-19) pandemic has resulted in a proliferation of clinical trials designed to slow the spread of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Many therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, Ebola, or for malaria that were developed decades ago and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here, we provide a foundation for cardiovascular and cardio-oncology physicians on the front line providing care to patients with COVID-19, so that they may better understand the emerging cardiovascular epidemiology and the biological rationale for the clinical trials that are ongoing for the treatment of patients with COVID-19., (© 2020 The Authors.)

A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19., Competing Interests: The authors declare that they have no competing interests., (© 2020 Elsevier Inc. All rights reserved.)

The coronavirus disease-2019 (COVID-19) pandemic has resulted in a proliferation of clinical trials designed to slow the spread of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Many therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, Ebola, or for malaria that were developed decades ago and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here, the authors provide a foundation for cardiovascular and cardio-oncology physicians on the front line providing care to patients with COVID-19, so that they may better understand the emerging cardiovascular epidemiology and the biological rationale for the clinical trials that are ongoing for the treatment of patients with COVID-19., (© 2020 The Authors.)

Use of systemic corticosteroids for the treatment for coronavirus disease 2019 (COVID-19) among chronic obstructive pulmonary disease (COPD) patients is not well described. A 58-year-old man with fever and progressive dyspnea was admitted to the Showa University Hospital, and showed severe respiratory failure which needed mechanical ventilation. His chest computed tomography scanning showed emphysema and bilateral ground-glass opacity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. He received 30 mg prednisolone for five days with antiviral drug of favipiravir, and was successfully extubated on day five. A SARS-CoV-2 polymerase chain reaction (PCR) test became negative on day 15. He was discharged on day 21. Serum IgM and IgG antibodies against SARS-CoV-2 converted to positive on day 7 and they kept positive on day 54 for both IgM and IgG. Combination treatment of short-course systemic corticosteroid and favipiravir might improve the prognosis for critically ill COVID-19 pneumonia with COPD without negative influence on viral clearance or antibody production., Competing Interests: The authors declare no conflicts of interest (COI) to disclose., (© 2020 The Authors.)

Due to the unprecedented public health crisis caused by COVID-19, our first contribution to the newly launching journal, Advances in Biomarker Sciences and Technology , has abruptly diverted to focus on the current pandemic. As the number of new COVID-19 cases and deaths continue to rise steadily around the world, the common goal of healthcare providers, scientists, and government officials worldwide has been to identify the best way to detect the novel coronavirus, named SARS-CoV-2, and to treat the viral infection - COVID-19. Accurate detection, timely diagnosis, effective treatment, and future prevention are the vital keys to management of COVID-19, and can help curb the viral spread. Traditionally, biomarkers play a pivotal role in the early detection of disease etiology, diagnosis, treatment and prognosis. To assist myriad ongoing investigations and innovations, we developed this current article to overview known and emerging biomarkers for SARS-CoV-2 detection, COVID-19 diagnostics, treatment and prognosis, and ongoing work to identify and develop more biomarkers for new drugs and vaccines. Moreover, biomarkers of socio-psychological stress, the high-technology quest for new virtual drug screening, and digital applications are described., Competing Interests: The authors declare that they have no potential conflict of interest., (© 2020 Published by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

One Health (OH) is a collaborative effort to attain optimal health for people, animals and the environment. The concept of OH is still in its infancy in Nepal but is increasingly growing. The Government of Nepal (GoN) has taken some initiatives to tackle burgeoning problems such as antimicrobial resistance, highly pathogenic avian influenza and rabies using OH approach but there are several challenges at the level of implementation. Few non-governmental organizations support GoN to promote an OH approach. The major bottlenecks in implementing OH in Nepal include poor organizational structure to support OH, absence of a legal framework to implement OH, poor coordination among different governmental agencies, insufficient technical expertise, poor data sharing mechanism across sectors, limited budget and poor understanding at political level. We encourage GoN to address these gaps and prioritize the health problems where OH approach would give the best outcome. Institutional and legal frameworks need to be created to effectively implement an OH approach in Nepal. Increasing awareness among policy makers including political leadership and increasing regular government budget for OH activities would be helpful to promote OH in Nepal.