Efficacy and Safety of Pirfenidone for Mitigation of Interstitial Lung Abnormalities in COVID-19 Patients: A Meta-Analysis.

BACKGROUND

Although post-COVID-19 interstitial lung abnormalities (ILAs) are common, the use of antifibrotic agents to prevent their onset and progression is controversial. We aimed to investigate the effectiveness and safety of pirfenidone to mitigate the onset and progression of ILAs in patients with severe COVID-19.

METHODS

We systematically searched literature published before July 21, 2025, from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biology Medicine, Weipu, and Wanfang databases, without language limitation. Randomized controlled trials and cohort studies that evaluated the effect of pirfenidone on COVID-19-induced ILAs were included. Risk of bias was determined using the Revised Cochrane Randomized Trial Risk Bias Tool Version 2 and the Newcastle-Ottawa Scale. The efficacy and safety of pirfenidone for ILAs in COVID-19 were analyzed by Review Manager 5.4 software.

RESULTS

Eight studies were included, comprising 335 patients in pirfenidone treatment groups and 302 controls. Risk of bias ranged from low to moderate. Pirfenidone significantly decreased chest high-resolution CT (HRCT) scores during early- and late-stage COVID-19 and significantly improved forced expiratory volume in 1 s, especially in late-stage COVID-19. Pirfenidone treatment was associated with statistically nonsignificant trends toward improved forced vital capacity and decreased all-cause mortality. Furthermore, HRCT scores, pulmonary function, and inflammatory cytokine levels following pirfenidone treatment were superior to those obtained after glucocorticoid therapy. The incidence of gastrointestinal adverse events was higher in the pirfenidone than the control group, but no serious adverse events or fatalities occurred.

CONCLUSION

Pirfenidone therapy may mitigate ILAs and preserve pulmonary function among survivors of COVID-19 pneumonia. Furthermore, pirfenidone exhibited acceptable safety and tolerability profiles.