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Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 1

Role of antifibrotics in post-COVID fibrosis: Yes or no?

Department of Respiratory Medicine, Apollo Hospitals, Chennai, Tamil Nadu, India

Date of Submission20-Jul-2021
Date of Acceptance30-Jul-2021
Date of Web Publication22-Sep-2021

Correspondence Address:
R Narasimhan
Department of Respiratory Medicine, Apollo Hospitals Chennai, Greams Road, Chennai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/japt.japt_33_21

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How to cite this article:
Narasimhan R. Role of antifibrotics in post-COVID fibrosis: Yes or no?. J Assoc Pulmonologist Tamilnadu 2021;4:1

How to cite this URL:
Narasimhan R. Role of antifibrotics in post-COVID fibrosis: Yes or no?. J Assoc Pulmonologist Tamilnadu [serial online] 2021 [cited 2022 Jan 28];4:1. Available from: http://www.japt.com/text.asp?2021/4/1/1/326415

Complete healing and fibrosis are the only two outcomes of any inflammation in the lung. Study by Vasarmidi et al. showed that around one-third of patients post-COVID develop fibrosis on discharge and the degree of fibrosis directly correlates with the duration of disease (>60% with disease duration of >3 weeks).

Post-COVID fibrosis is unique in that it is not progressive like idiopathic pulmonary fibrosis (IPF) or static like posttuberculous fibrosis. Disjointed and dysregulated inflammation with microangiopathy seems to be the major predictor of pulmonary fibrosis and thromboembolic phenomena in COVID. This is due to the excessive cytokine production in COVID causing activation of myofibroblasts leading to collagen deposition in extracellular matrix.

The prognosis of fibrosis in nonsevere COVID patients is favorable with more than 65% patients having resolved fibrosis in 4-week follow-up. It is the patients with severe disease who end up with symptomatic nonresolving fibrotic lung disease with low total lung capacity and DLCO. Around one-third of patients in recovery trial who were treated with 10 days of dexamethasone continued to be on oxygen support on day 28 and their outcomes were unknown. The use of long-term steroids for persistent inflammation post-COVID in these patients is perilous and predisposes for secondary infection. With the delta and delta plus variants of corona virus hovering large on the horizon at present with many patients affected by COVID-associated aspergillosis and mucormycosis, it is imperative that one has to think alternatives of steroid to manage the so called post-COVID or long COVID syndrome.

Pirfenidone and Nintedanib, the two novel drugs currently used in management of IPF are proposed for the management of post-COVID fibrosis as both share similar demographic, radiographic, and histopathologic features proven by studies. These agents prevent the decline of lung function and even have anti-oxidant and anti-inflammatory action when started in acute phase of COVID as shown by Collins et al.

The use of antifibrotics is not without criticisms, the notable ones being:

  1. Post-COVID fibrosis is essentially an organizing pneumonia and self-resolving in most cases
  2. The use of antifibrotics in these patients is only an extrapolation from results of studies done in IPF and progressive fibrosing-interstitial lung diseases
  3. There is no published data guideline recommending antifibrotics for post-COVID fibrosis
  4. The time to initiate antifibrotics is a still in debate. Antifibrotics use in early phase of infection is a concern: Pirfenidone/nintedanib both cause hepatotoxicity and nintedanib can cause bleeding in patients on anticoagulants
  5. It is not known whether antifibrotics should be used alone or in combination with steroids and other anti-inflammatory agents
  6. The follow-up of patients on antifibrotics and the time to stop anti-fibrotics is variable
  7. It is not known whether the patients with severe fibrosis will benefit from anti-fibrotics. The Western trials concerning pirfenidone and nintedanib (CAPACITY/ASCEND and INPULSIS/TOMORROW respectively) showed benefit only in mild-moderate IPF patients although in our country, most IPF patients present late and have shown better response to antifibrotics compared to steroids.

Although early anecdotal reports have been promising, randomized controlled trials are now underway to evaluate the efficacy of antifibrotics in management of post-COVID fibrosis. Until the results, it is only an individual expert call.


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