Longitudinal Plasma Proteomics Analysis Reveals Novel Candidate Biomarkers in Acute COVID-19.
Yassene MohammedDavid R GoodlettMatthew P ChengDonald C VinhTodd C LeeAllison McgeerDavid SweetKaren TranTerry LeeSrinivas MurthyJohn H BoydJoel SingerKeith R WalleyDavid M PatrickCurtis QuanSara IsmailLaetitia AmarAditya PalRayhaan BassawonLara FesdekjianKarine GouFrancois LamontagneJohn MarshallGreg HaljanRobert FowlerBrent W WinstonJames A Russellnull nullPublished in: Journal of proteome research (2022)
The host response to COVID-19 pathophysiology over the first few days of infection remains largely unclear, especially the mechanisms in the blood compartment. We report on a longitudinal proteomic analysis of acute-phase COVID-19 patients, for which we used blood plasma, multiple reaction monitoring with internal standards, and data-independent acquisition. We measured samples on admission for 49 patients, of which 21 had additional samples on days 2, 4, 7, and 14 after admission. We also measured 30 externally obtained samples from healthy individuals for comparison at baseline. The 31 proteins differentiated in abundance between acute COVID-19 patients and healthy controls belonged to acute inflammatory response, complement activation, regulation of inflammatory response, and regulation of protein activation cascade. The longitudinal analysis showed distinct profiles revealing increased levels of multiple lipid-associated functions, a rapid decrease followed by recovery for complement activation, humoral immune response, and acute inflammatory response-related proteins, and level fluctuation in the regulation of smooth muscle cell proliferation, secretory mechanisms, and platelet degranulation. Three proteins were differentiated between survivors and nonsurvivors. Finally, increased levels of fructose-bisphosphate aldolase B were determined in patients with exposure to angiotensin receptor blockers versus decreased levels in those exposed to angiotensin-converting enzyme inhibitors. Data are available via ProteomeXchange PXD029437.
Keyphrases
- inflammatory response
- angiotensin converting enzyme
- liver failure
- sars cov
- immune response
- respiratory failure
- smooth muscle
- drug induced
- cell proliferation
- coronavirus disease
- lipopolysaccharide induced
- angiotensin ii
- aortic dissection
- emergency department
- end stage renal disease
- toll like receptor
- lps induced
- hepatitis b virus
- chronic kidney disease
- ejection fraction
- big data
- cross sectional
- peritoneal dialysis
- extracorporeal membrane oxygenation
- mass spectrometry
- machine learning
- protein protein
- binding protein
- pi k akt
- patient reported outcomes
- quantum dots
- antibiotic resistance genes