Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy

Abstract

In December, 2019, reports emerged from Wuhan, China, of a severe acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By the end of April, 2020, over 3 million people had been confirmed infected, with over 1 million in the USA alone, and over 215 000 deaths. The symptoms associated with COVID-19 are diverse, ranging from mild upper respiratory tract symptoms to severe acute respiratory distress syndrome. The major risk factors for severe COVID-19 are shared with idiopathic pulmonary fibrosis (IPF), namely increasing age, male sex, and comorbidities such as hypertension and diabetes. However, the role of antifibrotic therapy in patients with IPF who contract SARS-CoV-2 infection, and the scientific rationale for their continuation or cessation, is poorly defined. Furthermore, several licensed and potential antifibrotic compounds have been assessed in models of acute lung injury and viral pneumonia. Data from previous coronavirus infections such as severe acute respiratory syndrome and Middle East respiratory syndrome, as well as emerging data from the COVID-19 pandemic, suggest there could be substantial fibrotic consequences following SARS-CoV-2 infection. Antifibrotic therapies that are available or in development could have value in preventing severe COVID-19 in patients with IPF, have the potential to treat severe COVID-19 in patients without IPF, and might have a role in preventing fibrosis after SARS-CoV-2 infection.

Figure

Potential mechanisms through which novel antifibrotic drugs could prevent the development of severe SARS-CoV-2 infection SARS-CoV-2 binds ACE2 in the alveolar lumen or on alveolar epithelial cells, and CD98 or RGD-binding integrins potentially facilitate cellular entry. Once within the cell, SARS-CoV-2 might use JNK and mTOR pathways for viral replication, which could activate the NLRP3 inflammasome to secrete IL-1 and IL-6 promoting severe disease. RGD=arg-gly-asp. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.