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Review
. 2021 Jul;302(1):228-240.
doi: 10.1111/imr.12977. Epub 2021 May 24.

COVID-19 and pulmonary fibrosis: A potential role for lung epithelial cells and fibroblasts

Alison E John  1   2 , Chitra Joseph  1 , Gisli Jenkins  1   2 , Amanda L Tatler  1
Affiliations
Review

COVID-19 and pulmonary fibrosis: A potential role for lung epithelial cells and fibroblasts

Alison E John et al. Immunol Rev. 2021 Jul.

Abstract

The COVID-19 pandemic rapidly spread around the world following the first reports in Wuhan City, China in late 2019. The disease, caused by the novel SARS-CoV-2 virus, is primarily a respiratory condition that can affect numerous other bodily systems including the cardiovascular and gastrointestinal systems. The disease ranges in severity from asymptomatic through to severe acute respiratory distress requiring intensive care treatment and mechanical ventilation, which can lead to respiratory failure and death. It has rapidly become evident that COVID-19 patients can develop features of interstitial pulmonary fibrosis, which in many cases persist for as long as we have thus far been able to follow the patients. Many questions remain about how such fibrotic changes occur within the lung of COVID-19 patients, whether the changes will persist long term or are capable of resolving, and whether post-COVID-19 pulmonary fibrosis has the potential to become progressive, as in other fibrotic lung diseases. This review brings together our existing knowledge on both COVID-19 and pulmonary fibrosis, with a particular focus on lung epithelial cells and fibroblasts, in order to discuss common pathways and processes that may be implicated as we try to answer these important questions in the months and years to come.

Keywords: COVID-19; SARS-CoV-2; epithelial cells; fibroblasts; lung fibrosis; lung remodeling.

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Conflict of interest statement

Prof Jenkins has received sponsored research agreements from: Biogen, Galecto, GSK, Medimmune. Plus personal fees from: Galapagos, Heptares, Boehringer Ingelheim, Pliant, Roche/Intermune, Medimmune, Pharmakea, Bristol Myers Squibb, Chiesi, Roche/Promedior. Plus collaborative awards from: RedX and Nordic Biosciences. Finally, he is an advisory board member for NuMedii.

Figures

FIGURE 1
FIGURE 1
Proposed mechanism of SARS‐CoV‐2‐associated fibrosis in the lung. INFECTION with SARS‐CoV‐2 causes damage to the alveolar epithelium and induces production of epithelial and macrophage derived inflammatory and immune cytokines leading to lung INJURY. Activated inflammatory cells and damaged epithelial cells contribute to the denudation of the basement membrane leading to migration and proliferation of interstitial fibroblasts in the alveolar space in response to TGFb, PDGF and IL‐6. SARS‐CoV‐2 infection also injures endothelial cells resulting in hemorrhage and leakage of plasma into the alveolus. In response to urokinase and PAI‐1 release from the damaged alveolar epithelium, coagulation pathways are activated leading to fibrin deposition. Persistent alveolar activation of TGFb, release of PDGF and IL‐6 from alveolar epithelia cells, immune cells and myofibroblasts leads to proliferation of myofibroblasts and development of FIBROSIS
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