Plasma proteomics gives new mechanistic insights into Long-COVID


Long-COVID syndrome (also known as post-acute sequelae of SARS-CoV-2 infection, PASC) refers to persistent symptoms or new symptoms that arise after recovering from the acute phase of COVID-19. While most people recover from COVID-19 within a few weeks, some continue to experience a range of physical and/or neurological symptoms that can last for several months or longer. In a study from researchers at Western University, Ontario, the Olink® Explore 3072 platform for high throughput protein biomarker discovery was used to analyze plasma proteomics in Long-COVID outpatients and compared to matched acutely ill COVID-19 (mild and severe) inpatients and healthy control subjects. Comparative expression data for over 3000 proteins was then deconvoluted with multiple bioinformatics tools to provide insights into the cell types, signaling mechanisms and organ-specific biology associated with protein changes in Long-COVID.


The bioinformatic analysis of differentially expressed proteins in Long-COVID outpatients indicated a redistribution of natural killer cells, with a dominant resting phenotype, and neutrophils that formed extracellular traps. This cell phenotype resetting was mirrored by prospective vascular events mediated by the hypoxia-regulated, pro-angiogenic proteins, ANGPT1 and VEGFA. Several of the key proteins identified from the Olink analysis (ANGPT1, VEGFA, CCR7, CD56, citrullinated histone 3, elastase) were also validated using serological methods in additional patient cohorts. Further analysis suggested that a vascular proliferative state associated with the hypoxia inducible factor 1 (HIF1)  pathway may be involved in the progression from acute COVID-19 to Long-COVID. The vasculo-proliferative process predicted in Long-COVID might contribute to changes in the organ-specific proteome that reflect the neurologic and cardiometabolic dysfunction frequently seen in this syndrome.

The authors concluded that this data provides a pathophysiological framework to better understand the functional heterogenicity of Long-COVID and provides clues to the neurological and cardio-metabolic basis of the disease. The differentially-expressed proteins identified represent a valuable resource for the exploration of biomarkers in Long-COVID and the development of potential therapeutic targets for its prevention and treatment, based on the potential pathophysiological mechanisms unveiled.



Iosef C, Knauer MJ, Nicholson M, et al. Plasma proteome of Long-COVID patients indicates HIF-mediated vasculo-proliferative disease with impact on brain and heart function. (2023) Journal of Translational Medicine, DOI: 10.1186/s12967-023-04149-9

Analyses of the plasma proteome, used as a surrogate for cellular signaling, unveiled potential organ-specific prognostic biomarkers and therapeutic targets

Iosef et al. (2023)

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