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      COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy?

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          Abstract

          Background

          Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines.

          Aims

          To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment.

          Method

          The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown.

          Results

          A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases ( Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases ( Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil , Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine.

          Conclusions

          Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches.

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          Most cited references585

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

            Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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              The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak

              Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                23 September 2020
                2020
                23 September 2020
                : 11
                : 581840
                Affiliations
                [1] 1Department of Pharmacy, Faculty of Health Sciences, University of Brasilia , Brasilia, Brazil
                [2] 2School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Liverpool, United Kingdom
                [3] 3School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin, Ireland
                [4] 4Biophysics and Biochemistry Center, Venezuelan Institute of Scientific Research , Caracas, Venezuela
                [5] 5Center of Health Sciences, Federal University of Espirito Santo , Vitória, Brazil
                [6] 6Faculty of Pharmacy, Medical University of Bialystok , Bialystok, Poland
                [7] 7Pharmacognosy and Phytotherapy, School of Pharmacy, University College of London , London, United Kingdom
                Author notes

                Edited by: Valentina Echeverria Moran, Bay Pines VA Healthcare System, United States

                Reviewed by: Helen Skaltsa, National and Kapodistrian University of Athens, Greece; François Chassagne, Emory University, United States

                *Correspondence: Dâmaris Silveira, damaris@ 123456unb.br ; Jose Maria Prieto-Garcia, J.M.PrietoGarcia@ 123456ljmu.ac.uk ; Michael Heinrich, m.heinrich@ 123456ucl.ac.uk

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                †These authors have contributed equally to this work

                Article
                10.3389/fphar.2020.581840
                7542597
                33071794
                f40a1963-b590-4adf-818e-93d808aca54f
                Copyright © 2020 Silveira, Prieto-Garcia, Boylan, Estrada, Fonseca-Bazzo, Jamal, Magalhães, Pereira, Tomczyk and Heinrich

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 July 2020
                : 28 August 2020
                Page count
                Figures: 0, Tables: 4, Equations: 0, References: 538, Pages: 44, Words: 27071
                Funding
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 10.13039/501100002322
                Award ID: CapesPrint 88887.4688871/2019-00
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                herbal medicine,coronavirus (2019-ncov),covid-19,benefit/risk assessment,respiratory diseases

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