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  Table of Contents    
Year : 2021  |  Volume : 38  |  Issue : 7  |  Page : 129-130  

Anti-fibrotic therapy for the treatment of pulmonary sequelae in patients healed by COVID-19

Department of Pharmaceutical, Perugia Usl Umbria 1, Perugia, Italy

Date of Submission01-Oct-2020
Date of Acceptance04-Oct-2020
Date of Web Publication06-Mar-2021

Correspondence Address:
Francesco Ferrara
Department of Pharmaceutical, Perugia Usl Umbria 1, Perugia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/lungindia.lungindia_803_20

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How to cite this article:
Vitiello A, Ferrara F. Anti-fibrotic therapy for the treatment of pulmonary sequelae in patients healed by COVID-19. Lung India 2021;38, Suppl S1:129-30

How to cite this URL:
Vitiello A, Ferrara F. Anti-fibrotic therapy for the treatment of pulmonary sequelae in patients healed by COVID-19. Lung India [serial online] 2021 [cited 2021 Apr 13];38, Suppl S1:129-30. Available from: https://www.lungindia.com/text.asp?2021/38/7/129/310911


Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2 or COVID-19) is the virus responsible for the current global pandemic. To date, 13.8 million people were infected and about 590,000 people died while 7.72 million were healed. The viral infection has been divided by scientific opinion into three phases: the first as asymptomatic or slightly symptomatic and the second and third with greater severity, characterized by a hyperinflammatory and fibrotic state, responsible for lung lesions, with in some cases being fatal.[1],[2],[3]

Several studies have revealed clinical features at different stages of the ongoing viral infection[4],[5],[6] however many pathophysiological aspects such as evolution and histological features of lung tissue during the convalescence period are not yet fully clear. Indeed, there is some evidence that residual lung lesions may be persistently present even years after recovery from SARS caused by SARS-CoV-2.[7] Epidemiological studies show that during the post-COVID-19 convalescence period many patients still have lung lesions caused by the presence of fibrotic tissue and that the complete healing process may occur slowly.[8] In addition, older patients need more time for complete resolution. Even if the virus is eradicated in patients who have recovered from COVID-19, total eradication of the virus, which causes lung lesions, does not completely exclude the development of a progressive and irreversible fibrotic interstitial lung disease.[9] Furthermore, even a relatively small degree of residual, but not progressive, pulmonary fibrosis could cause significant long-term morbidity and mortality, especially in the population of elderly patients who have had COVID-19.[10]

At this stage described, pirfenidone, a drug used for the treatment of idiopathic pulmonary fibrosis, could be of clinical benefit for a faster resolution of lung complications after COVID-19 eradication, due to its pleiotropic effects. In fact, pirfenidone has both antifibrotic and anti-inflammatory properties; has been shown to reduce the accumulation of inflammatory cells;[11] and is able to mitigate protein production and proliferation of fibroblasts and cytokines associated with fibrosis.[12] In addition, evidence has already demonstrated the efficacy of antifibrotics in patients with pathogenic prophylactic pathways caused by immune/inflammatory dysregulation, which may be similar to those present in the convalescent period.[13],[14],[15] For a possible relevance to the pulmonary outcomes of COVID-19, it should be noted that, recently, for pirfenidone, the revolutionary therapy status (which accelerates the drug approval process) for fibrous interstitial lung disease has been recognized by the Food and Drug Administration. It can be hypothesized that using antifibrotic therapy at the beginning of the convalescence period in patients with lung lesions could prevent further damage and accelerate full recovery.[16]

However, given the huge number of individuals affected by COVID-19, posteradication complications of COVID-19 should also be considered, and efforts should be made to understand the best treatment solutions. Interventional studies in this direction are needed to prevent a second wave of late and “secondary” mortality and morbidity associated with this devastating pandemic.

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Conflicts of interest

There are no conflicts of interest.

   References Top

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Liu D, Zhang W, Pan F, Li L, Yang L, Zheng D, et al. The pulmonary sequalae in discharged patients with COVID-19: A short-term observational study. Respir Res 2020;21:125.  Back to cited text no. 8
Spagnolo P, Balestro E, Aliberti S, Cocconcelli E, Biondini D, Casa GD, et al. Pulmonary fibrosis secondary to COVID-19: A call to arms? Lancet Respir Med 2020;8:750-2.  Back to cited text no. 9
George PM, Wells AU, Jenkins RG. Pulmonary fibrosis and COVID-19: The potential role for antifibrotic therapy. Lancet Respir Med 2020;8:807-15.  Back to cited text no. 10
George PM, Wells AU. Pirfenidone for the treatment of idiopathic pulmonary fibrosis. Expert Rev Clin Pharmacol 2017;10:483-91.  Back to cited text no. 11
Lancaster LH, de Andrade JA, Zibrak JD, Padilla ML, Albera C, Nathan SD, et al. Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis. Eur Respir Rev. 2017 Dec 6;26(146):170057. doi: 10.1183/16000617.0057-2017.  Back to cited text no. 12
Wells AU, Flaherty KR, Brown KK, Inoue Y, Devaraj A, Richeldi L, et al. Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: A randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Respir Med 2020;8:453-60.  Back to cited text no. 13
Ferrara F, Granata G, Pelliccia C, La Porta R, Vitiello A. The added value of pirfenidone to fight inflammation and fibrotic state induced by SARS-CoV-2. Eur J Clin Pharmacol 76, 1615–1618 (2020). https://doi.org/10.1007/s00228-020-02947-4  Back to cited text no. 14
Seifirad S. Pirfenidone: A novel hypothetical treatment for COVID-19. Med Hypotheses 2020;144:110005.  Back to cited text no. 15
Vitiello A, Pelliccia C, Ferrara F. COVID-19 Patients with Pulmonary Fibrotic Tissue: Clinical Pharmacological Rational of Antifibrotic Therapy [published online ahead of print, 2020 Aug 27]. SN Compr Clin Med. 2020;1-4. doi:10.1007/s42399-020-00487-7.  Back to cited text no. 16


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