COVID-19 Infection May Drive EC-like Myofibroblasts towards Myofibroblasts to Contribute to Pulmonary Fibrosis

Abstract

COVID-19 has an extensive impact on Homo sapiens globally. Patients with COVID-19 are at an increased risk of developing pulmonary fibrosis. A previous study identified that myofibroblasts could be derived from pulmonary endothelial lineage cells as an important cell source that contributes to pulmonary fibrosis. Here, we analyzed publicly available data and showed that COVID-19 infection drove endothelial lineage cells towards myofibroblasts in pulmonary fibrosis of patients with COVID-19. We also discovered a similar differentiation trajectory in mouse lungs after viral infection. The results suggest that COVID-19 infection leads to the development of pulmonary fibrosis partly through the activation of endothelial cell (EC)-like myofibroblasts.

Keywords: COVID-19; endothelial cells; pulmonary fibrosis.

Figure 1

ScRNA-seq identifies excess EC-like myofibroblasts differentiating towards myofibroblasts in pulmonary fibrosis of COVID-19 patients. (a) UMAP for the cell populations subclustered from the whole population of pulmonary cells. Arrows indicate the differentiation trajectory with alterations in cell compositions. (b) Violin plots of gene expression of lineage markers. Fn1, fibronectin 1. (c) Cell compositions of different populations in lungs of healthy humans or COVID-19 patients. (d) Pseudotemporal trajectories of the cell clusters. (e) The expression of genes along the single cell trajectories.

Figure 2

ScRNA-seq reveals ECs differentiating towards myofibroblasts in mouse lungs after influenza A viral infection. (a) UMAP for the cell populations subclustered from CD45-pulmonary cells along the time course of influenza A viral infection. Arrows indicate the differentiation trajectory with alterations in cell compositions. (b) Violin plots of the gene expression of VE-cadherin, CD31 and MGP in subclusters. (c) Violin plots of the gene expression of the myofibroblast lineage markers. Arrows indicate the markers of different stages of myofibroblast differentiation. (d) Cell compositions of different EC lineage populations in mouse lungs along the time course of influenza A viral infection. (e,f) Pseudotemporal trajectories of the cell clusters at day 0 (mock infection) and 3 after influenza A viral infection.