COVID-related fibrosis: insights into potential drug targets

ABSTRACT

Introduction

Lung injury in severe COVID-19 pneumonia can rapidly evolve to established pulmonary fibrosis, with prognostic implications in the acute phase of the disease and long-lasting impact on the quality of life of COVID-19 survivors. This is an emerging medical need, and it has been hypothesized that antifibrotic treatments could have a role in ameliorating the fibrotic process in the lungs of these patients.

Areas covered

The safety and efficacy of available antifibrotic drugs (nintedanib and pirfenidone) and novel promising agents are being assessed in several ongoing clinical trials that were performed either in critically ill patients admitted to intensive care, or in discharged patients presenting fibrotic sequalae from COVID-19. Literature search was performed using Medline and Clinicaltrials.org databases (2001–2021).

Expert opinion

Despite the strong rationale support the use of antifibrotic therapies in COVID-related fibrosis, there are several uncertainties regarding the timing for their introduction and the real risks/benefits ratio of antifibrotic treatment in the acute and the chronic phases of the disease. The findings of ongoing clinical trials and the long-term observation of longitudinal cohorts will eventually clarify the best management approach for these patients.

KEYWORDS:

• COVID-19
• post-COVID fibrosis
• COVID-related fibrosis
• idiopathic pulmonary fibrosis
• Pirfenidone
• Nintedanib

Article highlights

• The development of lung fibrosis is common in patients with severe COVID-19 pneumonia and is associated with residual respiratory impairment after hospital discharge.

• However, the natural course of Covid-related fibrosis is not fully known due to the paucity of long-term observational cohorts.

• Pro-fibrotic pathways can be triggered by several factors, including SARS-CoV-2 infection itself, the immune-mediated response, and the mechanical stress caused by ventilation.

• Several antifibrotic agents, including pirfenidone and nintedanib, are being tested in ongoing clinical trials for ameliorating the fibrotic process either in critically ill patients or in discharged patients with pulmonary fibrotic sequelae.

• Further research is warranted to clarify the benefits and risks of starting antifibrotic treatment in these patients, alongside its timing and duration.

This box summarizes key points contained in the article.

Declaration of interest

Dr. Sgalla reports personal fees from Boehringer Ingelheim outside the submitted work; Dr. Comes and Dr. Lerede have nothing to disclose; Dr. Richeldi reports personal fees and other from Boehringer Ingelheim, other from Fibrogen, personal fees from InterMune, personal fees from Cipla, personal fees from Vertex, other from GlaxoSmithKline, other from Astrazeneca, other from Sanofi-Aventis, other from Celgene, other from Prometic, other from Roche, from Takeda, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.