The effect of COVID-19 on the lungs could be similar to that of idiopathic pulmonary fibrosis (IPF), according to a new study published in eBioMedicine, part of The Lancet Discovery Science.
Both diseases show a similar gene expression pattern, an interleukin (IL)-15-centric cytokine storm, and cellular changes in alveolar type 2 cells including DNA damage, the arrest of the progenitor state induced by injury, and a senescence-associated secretory phenotype.
“We have revealed here that COVID-19 lung fibrosis resembles IPF,” the researchers wrote. The findings “are likely to spur the development of therapies for patients with IPF,” they said.
The study was fueled by the fact that around a third of people who recover from COVID-19 develop a mysterious fibrotic interstitial lung disease. The pathogenesis of this so-called post-COVID-19 lung disease is not well understood.
Read more about the etiology of IPF.
Using an artificial intelligence-guided approach, researchers led by Pradipta Ghosh, MD, professor of cellular and molecular medicine at the University of California San Diego School of Medicine analyzed more than 1000 human lung transcriptomic datasets associated with different lung conditions using viral pandemic signatures.
They then induced the immunocytopathic features they identified in adult lung organoids and hamsters and were able to effectively reverse them with anti-SARS-CoV-2 therapeutics.
When they analyzed the protein-protein interaction networks that they generated, the researchers identified endoplasmic reticulum stress as one of the common early triggers of both COVID-19 and IPF. They validated this finding by analyzing the lung tissue of deceased COVID-19 patients and a COVID-19 hamster model.
“Because unbiased computational methods identified the shared fundamental aspects of gene expression and cellular processes between COVID-19 and IPF, the impact of our findings is likely to go beyond COVID-19 or any viral pandemic,” the researchers wrote.
Sinha S, Castillo V, Espinoza CR, et al. COVID-19 lung disease shares driver AT2 cytopathic features with Idiopathic pulmonary fibrosis. eBioMedicine. 2022;82:104185. doi:10.1016/j.ebiom.2022.104185