Serum proteomic profiling reveals potential inflammatory biomarkers in long-COVID patients: a comparative analysis with healthy controls

OBJECTIVE: The highly transmissible severe acute respiratory syndrome-Coronavirus-2 was responsible for the 2020 COVID-19 pandemic. COVID-19 mostly affects the respiratory system; however, this infection also affects several other organs. In addition, the sequelae of this disease affect patients for several months after recovery, resulting in long-COVID syndrome. PATIENTS AND METHODS: In order to characterize the differences between healthy control individuals and long-COVID patients, proteomic profiling of the serum of both groups was performed by mass spectrometry. The obtained data were analyzed with multivariate and univariate statistical analyses. RESULTS: Initially, performing a partial latent square discriminant analysis (PLS-DA) made it possible to identify thirty-three proteins of interest, which were then subjected to a receiver operating characteristic (ROC) analysis. Four proteins were identified as potential standalone biomarkers: Sirtuin 1, Natriuretic Peptide B, Hemopexin, and Arachidonate 5-Lipoxygen-ase. Moreover, a multivariate ROC analysis identified a panel of biomarkers composed of Natriuretic Peptide B, Anterior Gradient 2 Protein, Adiponectin, Endothelin Converting Enzyme 1, Interferon Induced Transmembrane Protein 1, Mannose Binding Lectin 2, Prostaglandin-Endoperoxide Synthase 2, Pirin, Prostaglandin Reductase 1 and Cystatin C. CONCLUSIONS: The identified biomarkers are associated with inflammatory processes, corroborating literature evidence that long-COVID patients develop an inflammatory state that damages many tissues. Nevertheless, these data should be validated in a larger cohort.