Anti-fibrotic agents could be the game-changer for post-COVID-19 pulmonary fibrosis treatment


  • Pallab Chakraborty University of Calcutta, West Bengal, India
  • Kaustav Chakraborty Department of Zoology, S.B.S. Government College, Hili, Dakshin Dinajpur – 733126, West Bengal, India


COVID-19, Post-COVID-19 pulmonary fibrosis, Lung injury, Anti-fibrotic agents


More than 220 countries and territories are globally affected by the recent pandemic COVID-19 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is possibility of third wave of this pandemic as per epidemiological and public health experts. Besides that post-COVID-19 complications are alarming matter to look upon. Post-COVID-19 complications include several symptoms like as persistent fever; cough; fatigue; headache; attention disorder; dyspnea; anosmia; ageusia; chest pain discomfort; various respiratory illness; acute respiratory distress syndrome (ARDS) etc., and here the things to worry about is the development of pulmonary fibrosis after COVID-19. In some COVID-19 patients, hyper-inflammation in the form of ‘cytokine storm’ along with dysregulated immune response, alveolar epithelial tissue injury and wound repair collectively cause this secondary pulmonary fibrosis. Therefore, using anti-fibrotic agents e.g. pirfenidone, nintedanib and other natural compounds could be meaningful in these circumstances although their efficacy in treating COVID-19 is subject to more detailed laboratory research works. In this review article, we have discussed the progression of pulmonary fibrosis development which is triggered by COVID-19; probable solutions with anti-fibrotic agents including anti-fibrotic drugs, some well-known natural compounds, combined anti-fibrotic therapies; and the current challenges of this field.



Li H, Liu S, Yu X, Tang S, Tang C. Coronavirus disease 2019 (COVID-19): current status and future perspectives. Int J Antimicrob Agents. 2020; 5: 105951.

Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020; 63: 457–460.

Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. 2020; 5: 536–544.

Coronavirus data. Available from: ( [Cited 2021 August].

COVID-19_pandemic_data. Available from: Template: COVID-19_pandemic_data [Cited 2021 August].

Chakraborty K. COVID-19: Zoonotic Origin, Interspecies Transmission, Virus-Host Interaction and Animals Susceptibility to SARS-CoV-2. EC Pulmonol Respir Med. 2020; 9: 52-60.

Coronavirus types. Available from: [Cited May 2021]

Banerjee A, Kulcsar K, Misra V, Frieman M MK. Bats and coronaviruses. Viruses. 2019. 11: p41.

Mitra A. Investigations into the origin of SARS-CoV-2: an update. Curr Sci. 2021; 121: 77–84.

What Is Orthocoronavirinae? Available from: ( [Cited 2021 November].

Vishnupriya M, Naveenkumar M, Manjima K, Sooryasree NV, Saranya T, Ramya S, et al. Post-COVID pulmonary fibrosis: Therapeutic efficacy using with mesenchymal stem cells – How the lung heals. Eur Rev Med Pharmacol Sci. 2021; 25: 2748-2751.

George PM, Wells AU, Jenkins RG. Personal View Pulmonary fibrosis and COVID-19 : the potential role for antifibrotic therapy. Lancet Respir. 2020; 8: 807-815.

Coronavirus-2019/advice-for-public, available from- [Accessed on 2nd May 2021].

Vasarmidi E, Tsitoura E, Spandidos DA, Tzanakis N, Antoniou KM. Pulmonary fibrosis in the aftermath of the COVID-19 era. Exp Therap Med. 2020; 20: 2557-2560.

Grillo F, Barisione E, Ball L, Mastracci L, Fiocca R. Lung fibrosis: an undervalued finding in COVID-19 pathological series. Lancet Infect Dis. 2021; 21: e72.

Gentile F, Aimo A, Forfori F, Clemente A, Cademartiri F. COVID-19 and risk of pulmonary fibrosis: the importance of planning ahead. 2020. Eur J Preventive Cardiol. 2020; 27: 1442-1446.

Udwadia ZF, Koul PA, Richeldi L. Post-COVID lung fibrosis: The tsunami that will follow the earthquake. Lung India. 2021; 38: 41-47.

Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, et al. More than 50 long-term effects of COVID-19: a systemic review and meta-analysis. Sci Rep. 2021; 11: 16144.

Chaudhary S, Natt B, Bime C, Knox KS, Glassberg MK. Antifibrotics in COVID-19 Lung Disease: Let Us Stay Focused. Front Med. 2020; 7: 539.

Garcia-Revilla J, Deierborg T, Venero JL, Boza-Serrano A, Garcia-Revilla J, Boza-Serrano A. Hyperinflammation and Fibrosis in Severe COVID-19 Patients: Galectin-3, a Target Molecule to Consider. Front Immunol. 2020; 11: 1-6.

Antoniou K, Markopoulou K, Tzouvelekis A, Trachalaki A, Vasarmidi E, Organtzis J, et al. Efficacy and safety of nintedanib in a Greek multicentre idiopathic pulmonary fibrosis registry: A retrospective, observational, cohort study. ERJ Open Res. 2020; 6: 00172-2019.

Margaritopoulos GA, Trachalaki A, Wells AU, Vasarmidi E, Bibaki E, Papastratigakis G, et al. Pirfenidone improves survival in IPF: Results from a real-life study. BMC Pulm Med. 2018; 18: 177.

Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, et al. Genome composition China., and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe. 2020; 27: 325-328.

Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020; 9: 221-236.

Paules CI, Marston HD, Fauci AS. Coronavirus infections - more than just the common cold. JAMA. 2020; 323(8): 707-708.

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579: 270-273.

Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - the latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020; 91: 264-266.

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395: 507–513.

Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367: 1260–1263.

Mason RJ. Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J. 2020; 55: 9-11.

Kordzadeh-Kermani E, Khalili H, Karimzadeh I. Pathogenesis, clinical manifestations and complications of coronavirus disease 2019 (COVID-19). Fut Microbiol. 2020; 15: 1287-1305.

Times of India article on COVID19. linkk- [Accessed, April 2021].

Baas T, Taubenberger JK, Chong PY, Chui PKM. SARS-CoV virus-host interactions and comparative etiologies of acute respiratory distress syndrome as determined by transcriptional and cytokine profiling of formalin-fixed paraffin-embedded tissues. Interf Cytokine Res. 2006; 26: 399-317.

Wen Y, Deng BC, Zhou Y, Wang Y, Cui W, Wang W, et al. Immunological features in patients with pneumonitis due to influenza A H1N1 infection. J Investig Allergol Clin Immunol. 2011; 21: 44-50.

Xu J, Xu X, Jiang L, Dua K, Hansbro PM, Liu G. SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis. Resp Res. 2020; 21: 1-12.

Chuang H, Ho L, Harn H. Recent Findings on Cell-Based Therapies for COVID19-Related Pulmonary Fibrosis. Cell Transplant. 2021; 30: 1-4.

Albert RK, Smith B, Perlman CE SD. Is progression of pulmonary fibrosis due to ventilation‑induced lung injury? Crit Care Med Am Thorac Soc. 2019; 200: 140-151.

Mach WJ, Thimmesch AR, Pierce JT, Pierce JD. Consequences of hyperoxia and the toxicity of oxygen in the lung. Nurs Res Pract. 2011; 2011: 260482.

McDonald LT. Healing after Covid-19: Are Survivors at Risk for Development of Pulmonary Fibrosis? Am J Physiol Cell Mol Physiol. 2020; 320: L257-265.

Hadda V, Guleria R. Antifibrotic drugs for idiopathic pulmonary fibrosis: What we should know? Indian J Med Res. 2020; 152: 177-180.

Dimitroulis IA. Nintedanib: A novel therapeutic approach for idiopathic pulmonary fibrosis. Respir Care. 2014; 59: 1450-1455.

Hu Q, Noor M, Wong YF, Hylands PJ, Simmonds MS, Xu Q, et al. In vitro anti-fibrotic activities of herbal compounds and herbs. Nephrol Dial Transplant. 2009; 24: 3033-3041.

Agrawal PK, Agrawal C, Blunden G. Quercetin: Antiviral Significance and Possible COVID-19 Integrative Considerations. Nat Prod Commun. 2020; 15: p.1934578X20976293.

Huang F, Li Y, Leung ELH, Liu X, Liu K, Wang Q, et al. A review of therapeutic agents and Chinese herbal medicines against SARSCOV-2 (COVID-19). Pharmacol Res. 2020; 158: 104929.

Su H, Yao S, Zhao W, Li M, Liu J, Shang W, et al. Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro. Biorxiv preprint. 2020.

Hu S, Wang J, Zhang Y, Bai H, Wang C, Wang N HL. Three salvianolic acids inhibit 2019-nCoV spike pseudovirus viropexis by binding to both its RBD and receptor ACE2. J Med Virol. 2021; 93: 3143-3151.

Moghaddam E, Teoh BT, Sam SS, Lani R, Hassandarvish P, Chik Z, et al. Baicalin, a metabolite of baicalein with antiviral activity against dengue virus. Sci Rep. 2014; 4: 5452.

Vitug LC, Santiaguel J. Nintedanib as an adjunct treatment in improving lung function of post COVID-19 pulmonary fibrosis in an elderly patient: a case report. Chest. 2021; 160: A2166.

Colchicine and Post-COVID-19 Pulmonary Fibrosis. Available from:

Mahmud SH, Al-Mustanjid M, Akter F, Rahman MS, Ahmed K, Rahman MH, et al. Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 infections to idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease patients. Brief Bioinform. 2021; 22: 1-20.

Omote N, Kanemitsu Y, Inoue T, Yonezawa T, Ichihashi T, Shindo Y, et al. Successful Treatment with High-dose Steroids for Acute Exacerbation of Idiopathic Pulmonary Fibrosis Triggered by COVID-19: A Case Report. Intern Med Adv Publication. 2021; 10: 2169.

McGroder CF, Zhang D, Choudhury MA, Salvatore MM, D'Souza BM, Hoffman EA, et al. Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length. Thorax. 2021; 76: 1242.




How to Cite

Chakraborty , P. ., & Chakraborty , K. . (2022). Anti-fibrotic agents could be the game-changer for post-COVID-19 pulmonary fibrosis treatment. European Journal of Biological Research, 12(1), 1–10. Retrieved from



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