Rationale of Using Common Antifibrotic Therapy in Post COVID Fibrosis

Abstract

Different mechanisms of lung injury in COVID-19 have been described, like viral to immune-mediated mechanisms. Lung injury can be either subsequent to chronic inflammation or an idiopathic and genetically influenced process. Pulmonary fibrosis can occur with acute lung injury & a known sequela to ARDS. However, persistent radiological abnormalities after ARDS are of little clinical significance and have dwindled with protective lung ventilation. Pulmonary fibrosis is associated with permanent pulmonary architectural distortion and irreversible lung dysfunction. Available clinical, radiographic, and autopsy data has indicated that pulmonary fibrosis is central to severe acute respiratory distress syndrome (SARS) and MERS pathology, and current evidence suggests that pulmonary fibrosis could also complicate infection by SARS-CoV-2 The aim of this review is to explore the current literature on the pathogenesis of lung injury in COVID-19 infection, its risk factors & to find out the possible effective therapy within the existing medication. After literature review, we conclude that, currently there are no approved therapies for SARS COV2. Trials are based on drugs that are already approved for other diseases, have acceptable safety profiles or have been effective in animal studies against the other two highly pathogenic coronaviruses. Apart from the potent use of antivirals to reduce the viral effects, the use of antifibrotic therapies could also be under consideration based on the pulmonary fibrotic disease observed after COVID-19 recovery. Pirfenidone and Nintedanib are the two approved anti fibrotic drugs for Idiopathic Pulmonary Fibrosis (IPF). Despite having different modes of action, both are effective in attenuating the rate of lung function decline and are widely considered to improve life expectancy.
 J MEDICINE JAN 2021; 22 (1) : 46-50

Lung Fibrosis due to Coronavirus Disease 2019 Pneumonia with Critical Symptoms: A Case Report

“…To date, there is no specific therapy for postinflammatory pulmonary fibrosis due to COVID-19. Several therapies may be considered to reduce fibrosis due to COVID-19 such as pirfenidone, nintedanib, and mesenchymal stem cells [14], [15], but should be in context with clinical trial. In addition to antifibrotic therapy, respiratory support such as breathing exercise, pulmonary rehabilitation, and pulse oximetry self-monitoring can be performed to reduce complaints due to pulmonary fibrosis and improve quality of life.…”

Post Covid-19 pulmonary fibrosis: A review article

“…This pathway produces reactive oxygen species, antimicrobial compounds, and proinflammatory cytokines, which are responsible for the acute phase of inflammation. T-lymphocytes and other cells release IL-4 and IL-13, which activate the M2 pathway (11). This route results in the synthesis of cytokines and growth factors that are important in tissue healing.…”

“…This route results in the synthesis of cytokines and growth factors that are important in tissue healing. It also reduces the M1 pathway, which suppresses the inflammatory process, and it is essential in the creation of scar tissue (11). Inflammatory mediators such as Transforming growth factor-beta (TGF-)., vascular endothelial growth factor (VEGF)., interleukin 6 (IL-6).…”

“…activation of TGF-β1, which leads to proliferation, migration, and differentiation of fibroblasts into myofibroblasts, with the collagen and fibronectin deposition (12). This process may result in the restoration of normal pulmonary architecture, or it may result in pulmonary fibrosis with architectural distortion and irreversible lung impairment (11). Compared to non-smokers, smokers are 1.4 times more likely to develop severe COVID-19 symptoms, 2.4 times more likely to require ICU admission and mechanical ventilation, and times more likely to die.…”

“…Lymphopenia, leukocytosis, and elevated lactate dehydrogenase (LDH). levels in the blood associated with greater disease severity (11). Following acute lung injury, serum LDH levels have been utilized as a measure of disease severity.…”