Early intervention with anti-fibrotic pirfenidone is effective than corticosteroids in preventing pulmonary fibrosis in severe COVID pneumonia patients

Abstract

Background: The COVID-19 pandemic caused by SARS-CoV-2 has made nearly 120 million people sick with more than 2 million dead. Many survivors of severe COVID-19 are experiencing post-COVID complications beyond 4 weeks from the disease onset. The decrease in lung function and pulmonary fibrosis are the serious manifestations of COVID-19. The burden of even a relatively mild fibrotic change could have considerable morbidity and mortality, especially in the elderly and those with comorbidities. Aim: To evaluate the effect of early intervention with anti-fibrotic pirfenidone and corticosteroids in preventing pulmonary fibrosis in severe COVID pneumonia patients. Methods: This randomised open-label pilot trial was conducted was conducted at Government Medical College, Srinagar for evaluating the role of anti-fibrotic drugs in preventing post-COVID pulmonary fibrosis. In this study, 60 patients with severe COVID-19 infection were screened and randomised into two groups, one receiving anti-fibrotic drug– pirfenidone (n = 17) and other receiving corticosteroids (n = 19). The study participants were evaluated at the baseline and after 6 ± 1 week using 6-min walk test, spirometry and high-resolution computed tomography (HRCT). Results: The mean (±standard deviation [SD]) age of the pirfenidone and steroid group was 64.16 ± 11.36 and 67.19 ± 13.32 (P = 0.929), respectively. There were no significant differences in clinically relevant baseline characteristics at the time of enrolment in the two treatment groups. The initial CT severity score was 14.84 ± 4.031 and 14.81 ± 4.722 (P = 0.400) in pirfenidone and corticosteroids groups. The mean (±SD) baseline forced expiratory volume in the first second (FEV1) in pirfenidone and corticosteroid was 73.32 ± 18.10 and 71.71 ± 17.92 (P = 0.670), while FEV1/forced vital capacity was 95.89 ± 23.40 and 90.00 ± 21.09 (P = 0.920), respectively, between the two groups. The final fibrosis score was 115.52 ± 12.32 and 138.22 ± 43.90 (P = 0.004) in the pirfenidone and corticosteroids groups, respectively. At the 6th week, the proportion of patients who had died was less in the pirfenidone group as compared in the corticosteroid group (02 patients [11.76%] in the pirfenidone group vs. 08 patients [42.10%] P < 0.001). Conclusion: Pirfenidone, an anti-fibrotic agent, has a better outcome than corticosteroids in preventing post-COVID pulmonary fibrosis without serious adverse effects. Our study concludes that early initiation of pirfenidone therapy in patients with severe COVID-19 infection, especially those at higher risk like the elderly and those with co-morbidities has a better treatment and survival outcome compared to corticosteroids.