Increase of mast cells in COVID-19 pneumonia may contribute to pulmonary fibrosis and thrombosis

Histopathology. 2023 Feb;82(3):407-419. doi: 10.1111/his.14838. Epub 2022 Nov 27.


Aims: Lung tissue from COVID-19 patients shares similar histomorphological features with chronic lung allograft disease, also suggesting activation of autoimmune-related pathways in COVID-19. To more clearly understand the underlying spectrum of pathophysiology in COVID-19 pneumonia, we analysed mRNA expression of autoimmune-related genes in post-mortem lung tissue from COVID-19 patients.

Methods and results: Formalin-fixed, paraffin-embedded lung tissue samples of 18 COVID-19 patients and eight influenza patients were used for targeted gene expression profiling using NanoString technology. Multiplex immunofluorescence for tryptase and chymase was applied for validation. Genes related to mast cells were significantly increased in COVID-19. This finding was strengthened by multiplex immunofluorescence also showing a significant increase of tryptase- and chymase-positive cells in COVID-19. Furthermore, receptors for advanced glycation end-products (RAGE) and pro-platelet basic protein (PPBP) were up-regulated in COVID-19 compared to influenza. Genes associated with Type I interferon signalling showed a significant correlation to detected SARS-CoV2 pathway-related genes. The comparison of lung tissue samples from both groups based on the presence of histomorphological features indicative of acute respiratory distress syndrome did not result in finding any specific gene or pathways.

Conclusion: Two separate means of measuring show a significant increase of mast cells in SARS-CoV-2-infected lung tissue compared to influenza. Additionally, several genes involved in fibrosis and thrombosis, among which are RAGE and PPBP, are up-regulated in COVID-19. As mast cells are able to induce thrombosis and fibrosis, they may play an important role in the pathogenesis of COVID-19.

Keywords: COVID-19; autoimmunity; fibrosis; gene expression profiling; genomics; mast cells; thrombosis.

MeSH terms

  • COVID-19* / complications
  • COVID-19* / pathology
  • Chymases
  • Fibrosis
  • Humans
  • Influenza, Human* / pathology
  • Mast Cells* / pathology
  • Pulmonary Fibrosis* / etiology
  • Pulmonary Fibrosis* / pathology
  • RNA, Viral
  • SARS-CoV-2
  • Thrombosis* / etiology
  • Thrombosis* / pathology
  • Tryptases


  • Chymases
  • RNA, Viral
  • Tryptases