Tag: proteins

Several De-Regulated Chemokine Pathways Characterize Long COVID Syndrome

Abstract:

Introduction: The diagnosis of the Long COVID multi-organ syndrome is impeded by lack of circulating biomarkers. Hypothesis: We hypothesized, that post-COVID syndrome is associated with circulating protein de-regulation, enabling diagnosis of long COVID syndrome.

Methods: Consecutive patients (70% female, 55±8y) with long COVID syndrome (n=70, 64.3% female, 49±6y) and non-diseased, non-vaccinated healthy controls (n=23, 70% female, 55±8y) of the Vienna POSTCOV Registry (EC 1008/2021) were included, and blood samples were collected. Proteomics was performed by using the Olink proteomics technology (Olink Proteomics, Uppsala, Sweden), by using cardiovascular, Immunologic, inflammation and neurologic protein (3×96 protein) panels. Protein-protein interaction network were built by selecting the significantly dysregulated proteins from the 4 panels, and were classified into functional groups.

Results: Multiplex protein panel revealed 34 significantly de-regulated proteins as compared to controls. Gene ontology categorized the 29 upregulated proteins into several pathways with significant (false discovery rate <0.05) functional enrichment in biological processes (eg. death-inducing signaling complex assembly or positive regulation of tumor necrosis factor-mediated signaling pathway), and in molecular function (catalytic activity). Downregulated proteins were in association with chemokine-mediated signaling pathway and chemokine activity (Figure). KEGG pathway analyses revealed upregulated apoptosis, TNF- and NF-κB signaling pathways, but unchanged ACE2 receptors in patients with long COVID syndrome.

Conclusions: Several de-regulated chemokine pathways characterize long COVID syndrome and may serve as a combined biomarker panel for long COVOD diagnosis and target drug prediction.

Source: Mariann Gyongyosi, Emilie Han, Dominika Lukovic, Kevin Hamzaraj, Jutta K Bergler-Klein and Ena Hasimbegovic. Several De-Regulated Chemokine Pathways Characterize Long COVID Syndrome. Originally published 6 Nov 2023,Circulation. 2023;148:A18340 https://www.ahajournals.org/doi/abs/10.1161/circ.148.suppl_1.18340

Organ and cell-specific biomarkers of Long-COVID identified with targeted proteomics and machine learning

Abstract:

Background: Survivors of acute COVID-19 often suffer prolonged, diffuse symptoms post-infection, referred to as “Long-COVID”. A lack of Long-COVID biomarkers and pathophysiological mechanisms limits effective diagnosis, treatment and disease surveillance. We performed targeted proteomics and machine learning analyses to identify novel blood biomarkers of Long-COVID.

Methods: A case-control study comparing the expression of 2925 unique blood proteins in Long-COVID outpatients versus COVID-19 inpatients and healthy control subjects. Targeted proteomics was accomplished with proximity extension assays, and machine learning was used to identify the most important proteins for identifying Long-COVID patients. Organ system and cell type expression patterns were identified with Natural Language Processing (NLP) of the UniProt Knowledgebase.

Results: Machine learning analysis identified 119 relevant proteins for differentiating Long-COVID outpatients (Bonferonni corrected P < 0.01). Protein combinations were narrowed down to two optimal models, with nine and five proteins each, and with both having excellent sensitivity and specificity for Long-COVID status (AUC = 1.00, F1 = 1.00). NLP expression analysis highlighted the diffuse organ system involvement in Long-COVID, as well as the involved cell types, including leukocytes and platelets, as key components associated with Long-COVID.

Conclusions: Proteomic analysis of plasma from Long-COVID patients identified 119 highly relevant proteins and two optimal models with nine and five proteins, respectively. The identified proteins reflected widespread organ and cell type expression. Optimal protein models, as well as individual proteins, hold the potential for accurate diagnosis of Long-COVID and targeted therapeutics.

Source: Patel MA, Knauer MJ, Nicholson M, Daley M, Van Nynatten LR, Cepinskas G, Fraser DD. Organ and cell-specific biomarkers of Long-COVID identified with targeted proteomics and machine learning. Mol Med. 2023 Feb 21;29(1):26. doi: 10.1186/s10020-023-00610-z. PMID: 36809921; PMCID: PMC9942653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942653/ (Full text)