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      Pirfenidone: A novel hypothetical treatment for COVID-19

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      Publication date (Electronic):
      Journal: Medical Hypotheses
      Publisher: Elsevier Ltd.
      Keywords: COVID-19, Coronavirus Disease 2019, COVID-19-SARS, Coronavirus Disease 2019 – Severe Acute Respiratory Syndrome, ARDS, Acute respiratory distress syndrome, IPF, Idiopathic Pulmonary Fibrosis, TGF-β1, Transforming growth factor β1, TGF, Connective tissue growth factor, PDGF, Platelet-derived growth factors, TNF-α, Tumor necrosis factor-α, ADP, Adenosin Diphosphate, ACE, Angiotensin Converting Enzyme, NADPH, Nicotinamide adenine dinucleotide phosphate, ECM, Extracellular matrix, FDA, US Food and Drug Administration, COVID-19, Pirfenidone, Treatment, Cytokine storm, Oxidative stress, Inflammation, Angiotensin converting enzyme receptor, Acute respiratory distress syndrome

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Cytokine storm, multiorgan failure, and particularly acute respiratory distress syndrome (ARDS) is the leading cause of mortality and morbidity in patients with COVID-19. A fulminant ARDS kills the majority of COVID-19 victims.

          Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone), is a novel anti-fibrotic agent with trivial adverse effects. Pirfenidone is approved for the treatment of Idiopathic Pulmonary Fibrosis (IPF) for patients with mild to moderate disease. Pirfenidone could inhibit apoptosis, downregulate ACE receptors expression, decrease inflammation by several mechanisms and ameliorate oxidative stress and hence protect pneumocytes and other cells from COVID-19 invasion and cytokine storm simultaneously. Based on the pirfenidone mechanism of action and the known pathophysiology of COVID-19, I believe that pirfenidone has the potential for the treatment of COVID-19 patients.

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

          Fei Zhou, Ting Yu, Ronghui Du … (2020)
          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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            The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality

            Chi Zhang, Zhao Wu, Jia-Wen Li … (2020)
            Highlights • Pathogenesis of cytokine release syndrome in severe COVID-19 patients • The key role of IL-6 in cytokine release syndrome • Propose possible drugs IL-6R antagonist Tocilizumab for severe COVID-19
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              Is Open Access

              Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients

              Yong Xiong, Yuan Liu, Liu Cao … (2020)
              ABSTRACT Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients’ lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.
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                Author and article information

                Contributors
                Soroush Seifirad
                Journal
                Journal ID (nlm-ta): Med Hypotheses
                Journal ID (iso-abbrev): Med. Hypotheses
                Title: Medical Hypotheses
                Publisher: Elsevier Ltd.
                ISSN (Print): 0306-9877
                ISSN (Electronic): 1532-2777
                Publication date PMC-release: 17 June 2020
                Publication date (Print): November 2020
                Publication date (Electronic): 17 June 2020
                Volume: 144
                Page: 110005
                Affiliations
                Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
                Department of Medicine, Hackensack Meridian Health Mountainside Medical Center, Montclair, NJ, USA
                Article
                Publisher ID: S0306-9877(20)30838-0 Publisher ID: 110005
                DOI: 10.1016/j.mehy.2020.110005
                PMC ID: 7297676
                PubMed ID: 32575019
                SO-VID: 0e3524da-d3c4-4b73-9df5-ee6358809774
                Copyright © © 2020 Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 15 April 2020
                Date revision received : 4 June 2020
                Date accepted : 15 June 2020
                Categories
                Subject: Article

                ScienceOpen disciplines: Medicine
                Keywords: covid-19, coronavirus disease 2019,covid-19-sars, coronavirus disease 2019 – severe acute respiratory syndrome,ards, acute respiratory distress syndrome,ipf, idiopathic pulmonary fibrosis,tgf-β1, transforming growth factor β1,tgf, connective tissue growth factor,pdgf, platelet-derived growth factors,tnf-α, tumor necrosis factor-α,adp, adenosin diphosphate,ace, angiotensin converting enzyme,nadph, nicotinamide adenine dinucleotide phosphate,ecm, extracellular matrix,fda, us food and drug administration,covid-19,pirfenidone,treatment,cytokine storm,oxidative stress,inflammation,angiotensin converting enzyme receptor,acute respiratory distress syndrome
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: covid-19, coronavirus disease 2019, covid-19-sars, coronavirus disease 2019 – severe acute respiratory syndrome, ards, acute respiratory distress syndrome, ipf, idiopathic pulmonary fibrosis, tgf-β1, transforming growth factor β1, tgf, connective tissue growth factor, pdgf, platelet-derived growth factors, tnf-α, tumor necrosis factor-α, adp, adenosin diphosphate, ace, angiotensin converting enzyme, nadph, nicotinamide adenine dinucleotide phosphate, ecm, extracellular matrix, fda, us food and drug administration, covid-19, pirfenidone, treatment, cytokine storm, oxidative stress, inflammation, angiotensin converting enzyme receptor, acute respiratory distress syndrome

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