Journal
JOURNAL OF PROTEOME RESEARCH
Volume 20, Issue 10, Pages 4667-4680Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.1c00215
Keywords
COVID-19; SARS-CoV-2; mass spectrometry; longitudinal; proteomics; metabolomics
Categories
Funding
- Ministry of Science and Technology, Department of Biotechnology, Government of India [BT/PR41020/COT/142/14/2020]
- IRCC, IIT Bombay [RD/0520IRCCHC0-006]
- Department of Biotechnology [BT/PR13114/INF/22/206/2015]
- IIT Bombay-IPDF
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By utilizing proteomic and metabolomic analysis, dysregulated proteins, peptides, and metabolites were identified in severe COVID-19 patients, with alterations in complement and coagulation cascade, platelet aggregation, myeloid leukocyte activation pathway, and arginine metabolism pathways highlighted. The study suggests targeting leukocyte activation and arginine metabolism as potential therapeutic strategies for COVID-19.
Severe coronavirus disease 2019 (COVID-19) infection may lead to lung injury, multi-organ failure, and eventually death. Cytokine storm due to excess cytokine production has been associated with fatality in severe infections. However, the specific molecular signatures associated with the elevated immune response are yet to be elucidated. We performed a mass-spectrometry-based proteomic and metabolomic analysis of COVID-19 plasma samples collected at two time points. Using Orbitrap Fusion LCMS/MS-based label-free proteomic analysis, we identified around 10 significant proteins, 32 significant peptides, and 5 metabolites that were dysregulated at the severe time points. Few of these proteins identified by quantitative proteomics were validated using the multiple reaction monitoring (MRM) assay. Integrated pathway analysis using distinct proteomic and metabolomic signatures revealed alterations in complement and coagulation cascade, platelet aggregation, myeloid leukocyte activation pathway, and arginine metabolism. Further, we highlight the role of leukocyte activation and arginine metabolism in COVID-19 pathogenesis and targeting these pathways for COVID-19 therapeutics.
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