Tissue-specific pathway activities: A retrospective analysis in COVID-19 patients

Nhung Pham, Finterly Hu, Chris T Evelo, Martina Kutmon*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The ACE2 receptors essential for SARS-CoV-2 infections are expressed not only in the lung but also in many other tissues in the human body. To better understand the disease mechanisms and progression, it is essential to understand how the virus affects and alters molecular pathways in the different affected tissues. In this study, we mapped the proteomics data obtained from Nie X. et al. (2021) to the pathway models of the COVID-19 Disease Map project and WikiPathways. The differences in pathway activities between COVID-19 and non-COVID-19 patients were calculated using the Wilcoxon test. As a result, 46% (5,235) of the detected proteins were found to be present in at least one pathway. Only a few pathways were altered in multiple tissues. As an example, the Kinin-Kallikrein pathway, an important inflammation regulatory pathway, was found to be less active in the lung, spleen, testis, and thyroid. We can confirm previously reported changes in COVID-19 patients such as the change in cholesterol, linolenic acid, and arachidonic acid metabolism, complement, and coagulation pathways in most tissues. Of all the tissues, we found the thyroid to be the organ with the most changed pathways. In this tissue, lipid pathways, energy pathways, and many COVID-19 specific pathways such as RAS and bradykinin pathways, thrombosis, and anticoagulation have altered activities in COVID-19 patients. Concluding, our results highlight the systemic nature of COVID-19 and the effect on other tissues besides the lung.

Original languageEnglish
Article number963357
Number of pages12
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 15 Sept 2022

Keywords

  • Angiotensin-Converting Enzyme 2
  • Anticoagulants
  • Arachidonic Acid
  • Bradykinin/metabolism
  • COVID-19
  • Humans
  • Kallikreins/metabolism
  • Male
  • Peptidyl-Dipeptidase A/metabolism
  • Renin-Angiotensin System
  • Retrospective Studies
  • SARS-CoV-2
  • alpha-Linolenic Acid

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