Pharmacological approaches to pulmonary fibrosis following COVID-19

Abstract

Background: In the past few years, COVID-19 became the leading cause of morbidity and mortality worldwide. Although the World Health Organization has declared an end to COVID-19 as a public health emergency, it can be expected, that the emerging new cases at the top of previous ones will result in an increasing number of patients with post-COVID-19 sequelae. Despite the fact that the majority of patients recover, severe acute lung tissue injury can in susceptible individuals progress to interstitial pulmonary involvement. Our goal is to provide an overview of various aspects associated with the Post-COVID-19 pulmonary fibrosis with a focus on its potential pharmacological treatment options.Areas covered: We discuss epidemiology, underlying pathobiological mechanisms, and possible risk and predictive factors that were found to be associated with the development of fibrotic lung tissue remodelling. Several pharmacotherapeutic approaches are currently being applied and include anti-fibrotic drugs, prolonged use or pulses of systemic corticosteroids and non-steroidal anti-inflammatory and immunosuppressive drugs. In addition, several repurposed or novel compounds are being investigated. Fortunately, clinical trials focused on pharmacological treatment regimens for post-COVID-19 pulmonary fibrosis have been either designed, completed or are already in progress. However, the results are contrasting so far. High quality randomised clinical trials are urgently needed with respect to the heterogeneity of disease behaviour, patient characteristics and treatable traits.Conclusion: The Post-COVID-19 pulmonary fibrosis contributes to the burden of chronic respiratory consequences among survivors. Currently available pharmacotherapeutic approaches mostly comprise repurposed drugs with a proven efficacy and safety profile, namely, corticosteroids, immunosuppressants and antifibrotics. The role of nintedanib and pirfenidone is promising in this area. However, we still need to verify conditions under which the potential to prevent, slow or stop progression of lung damage will be fulfilled.

Short- and Long-Term Chest-CT Findings after Recovery from COVID-19: A Systematic Review and Meta-Analysis

“…Post-COVID pulmonary fibrosis, with an incidence ranging between 5 and 75%, contributes to the burden of chronic respiratory issues among survivors [ 89 ]. Its pathophysiology likely stems from the local proinflammatory environment caused by macrophage and immune cell infiltration in the lungs, which disrupts the natural homeostatic tissue-repair functions [ 90 ].…”

“…Our study identified severe COVID-19 as a risk factor for residual pulmonary fibrosis, which is consistent with other studies [ 91 , 92 ]. Although there is no consensus on treatment, antifibrotic agents may benefit these patients [ 89 ].…”

Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19

“…Lung disease improved in approximately one third of patients in group D, and CD4+ T cells were implicated in this process. Regarding more advanced disease, the current view is that post-COVID fibrosis is non-progressive 53,65 ; however, further examination of its multi-factorial etiology, variable response to treatment 5,66 , long-term recovery, and post-acute immune drivers is warranted. The utility of CXCL13 as an early biomarker of lung disease, its role in divergent clinical courses, and potential for therapeutic targeting are all of interest in this context.…”

Pulmonary Sequelae of COVID-19: Focus on Interstitial Lung Disease

“…Notably, the PINCER trial (NCT04856111) will compare these established antifibrotic treatments in a phase 4 head-to-head study evaluating the safety and efficacy of Pirfenidone versus Nintedanib. Several case reports have looked to assess the role of antifibrotics in acute COVID-19 illness with variable results [ 79 ]. A recently published study randomized symptomatic post-COVID-19 patients (at 12 weeks post discharge) to either Nintedanib or Pirfenidone.…”