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

Abstract

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.

Consensus transcriptional regulatory networks of coronavirus-infected human cells

“…Epithelial to mesenchymal transition (EMT) is the process by which epithelial cells lose their polarity and adhesive properties and acquire the migratory and invasive characteristics of mesenchymal stem cells 69 . EMT is known to contribute to pulmonary fibrosis 70 , acute interstitial pneumonia 71 and acute respiratory distress syndrome (ARDs) 72 , all of which have been reported in connection with SARS2 infection in COVID-19 [73][74][75] . We were interested to note therefore that significant HCT intersections for three well characterized EMT-promoting transcription factors were specific to SARS2 infection (q-values: SNAI2/Slug 76 , 2e-2; EPAS1/HIF2α 77 , 9e-9; LEF1 78 , 1e-3; Fig To investigate the connection between SARS2 infection and EMT implied by these HCT intersections, we then computed intersections between the individual viral HCTs and a list of 335 genes manually curated from the research literature as EMT markers 80 (figshare File F1, section 11).…”

CT Chest at discharge in Hospitalized Covid-19 patients: Should we worry about the long term evolution of parenchymal lesions?

“…There was no signi cant difference between patients requiring and not requiring ICU admission regarding the age, BMI and CT score at admission. The median time between onset of symptoms and admission was 7.9 days [0-19] and the median hospital stay was 12 days ; respectively 18 days [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] for ICU patients and 9 days [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] for non ICU patients (p=0.0006). All CT chest at discharge (100%) showed persistent parenchymal abnormalities regardless of the time of clinical recovery or ICU requirement.…”

“…Given the number of infected patients, careful consideration of the organisation of recovery of lung function follow-up is needed 11 . We should remain vigilant and the question of anti brotic agent usefulness may be asked 12 .…”

In silico immune infiltration profiling reveals the role of naïve B cells in lung tissues of COVID-19 patients

“…Rationale and design of an in silico simulated immune cell in ltration pro ling study Nearly all of the patients who died from COVID-19 had severe lung tissue damage and pulmonary brosis 29 . On the other hand, mortality in IPF is generally the result of progressive brotic lung disease.…”