Increase of Mast Cells in COVID-19 Pneumonia may Contribute to Pulmonary Fibrosis and Thrombosis

Leonoor V Wismans, Boaz Lopuhaä*, Willem de Koning, Hazra Moeniralam, Matthijs van Oosterhout, Carmen Ambarus, Frederik N Hofman, Thijs Kuiken, Henrik Endeman, Dana A M Mustafa, Jan H von der Thüsen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

AIMS: Lung tissue from COVID-19 patients shares similar histomorphological features with chronic lung allograft disease, suggesting activation of autoimmune related pathways in COVID-19 as well. To better understand the underlying spectrum of pathophysiology in COVID-19 pneumonia, we analyzed mRNA expression of autoimmune-related genes in post-mortem lung tissue from COVID-19 patients.

METHODS AND RESULTS: Formalin-fixated, paraffin-embedded lung tissue samples of 18 COVID-19 patients and 8 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 showing a significant increase of tryptase- and chymase positive cells in COVID-19 as well. Furthermore, RAGE (receptor for advanced glycation end-products) and PPBP (pro-platelet basic protein) were upregulated in COVID-19 compared to influenza. Genes associated with type I interferon signaling 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 ARDS did not result in finding any specific gene or pathways.

CONCLUSION: Two separate means of measuring show 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 upregulated 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.

Original languageEnglish
Pages (from-to)407-419
Number of pages13
JournalHistopathology
Volume82
Issue number3
DOIs
Publication statusE-pub ahead of print - 11 Nov 2022

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