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      The added value of pirfenidone to fight inflammation and fibrotic state induced by SARS-CoV-2 : Anti-inflammatory and anti-fibrotic therapy could solve the lung complications of the infection?

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          Abstract

          Aim

          SARS-CoV-2 infection has been divided by scientific opinion into three phases: the first as asymptomatic or slightly symptomatic and the second and the third with greater severity, characterized by a hyperinflammatory and fibrotic state, responsible for lung lesions, in some cases fatal. The development of antiviral drugs directed against SARS-CoV-2 and effective vaccines is progressing; meanwhile, the best pharmacological objective is related to the management of all the complications caused by this viral infection, mainly controlling the inflammatory and fibrotic state and preventing the infection from moving into the most serious phases.

          Subject and method

          Describe the scientific rationale related to the use of an antifibrotic therapy with pirfenidone, as monotherapy and/or in combination with anti-inflammatory drugs to manage and control complications of SARS-CoV-2 infection.

          Results

          Based on the scientific literature and epidemiological results and considering the pathophysiological, biological, and molecular characteristics of SARS-CoV-2, an antifibrotic drug such as pirfenidone as monotherapy or in combination with anti-inflammatory drugs can be (acting early, at the right doses and at the right time) therapeutically effective to avoid serious complications during viral infection. The same approach can also be effective as postinfection therapy in patients with residual pulmonary fibrotic damage. Management of inflammation and fibrotic status with a combination therapy of pirfenidone and IL-6 or IL-1 inhibitors could represent a pharmacological synergy with added value.

          Conclusion

          In this article, we consider the role of antifibrotic therapy with pirfenidone in patients with SARS-CoV-2 infection on going or in the stage of postinfection with pulmonary fibrotic consequences. The scientific rationale for its use is also described.

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Na Zhu, Dingyu Zhang, Wenling Wang … (2020)
            Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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              Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

              Nanshan Chen, Min Zhou, Xuan Dong … (2022)
              Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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                Author and article information

                Contributors
                Francesco Ferrara:
                ORCID: http://orcid.org/0000-0001-9298-6783
                francesco.ferrara@uslumbria1.it
                Journal
                Journal ID (nlm-ta): Eur J Clin Pharmacol
                Journal ID (iso-abbrev): Eur. J. Clin. Pharmacol
                Title: European Journal of Clinical Pharmacology
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0031-6970
                ISSN (Electronic): 1432-1041
                Publication date (Electronic): 27 June 2020
                Pages: 1-4
                Affiliations
                [1 ]Usl Umbria 1, Perugia, Italy
                [2 ]Asl Salerno, Salerno, Italy
                [3 ]Usl Umbria 2, Terni, Italy
                [4 ]Asur Marche, Ancona, Italy
                Author information
                http://orcid.org/0000-0001-9298-6783
                Article
                Publisher ID: 2947
                DOI: 10.1007/s00228-020-02947-4
                PMC ID: 7320911
                PubMed ID: 32594204
                SO-VID: 259b4385-125e-4651-98fa-f71275e12e1b
                Copyright © © Springer-Verlag GmbH Germany, part of Springer Nature 2020
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 1 May 2020
                Date accepted : 23 June 2020
                Categories
                Subject: Point of View

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: pirfenidone,fibrotic,inflammation,cytokine,interleukin,sars-cov-2
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: pirfenidone, fibrotic, inflammation, cytokine, interleukin, sars-cov-2

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