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 (3x96 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.
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