Abstract

Introduction: COVID-19 can be worsened by hyper-production of cytokines accompanied by increased level of oxidative stress. The aim of this study was to investigate the correlation between a set of cytokines and the markers of the oxidative stress. Methods: The levels of cytokines IL-2, IL-4, IL-6, IL8, IL-10, VEGF, IFN-γ, TNF-α, IL-1α, MCP-1 and EGF were determined by using High Sensitivity Evidence Investigator™ Biochip Array technology. The oxidative stress parameters (d-ROM, PAT, OS index) were measured in serum on FRAS5 analytical photometric system. Results: IL-6, IL-8, IL-10, VEGF, MCP-1 and EGF were significantly higher (p<0.05) in the patients with severe COVID-19 with increased levels of IL-2, IFN-y, TNF-α and IL-1α. The d-ROM, OS index, and PAT were significantly higher (p<0.05) in severe COVID-19 patients. IL-6 demonstrated the strongest correlation with all of the markers of the oxidative stress, d-ROM (r=0.9725, p=0.0001), PAT (r=0.5000, p=0.0001) and OS index (r=0.9593, p=0.012). Similar behavior was evidenced between IFN-y and d-ROM (r=0.4006, p=0.0001), PAT (r=0.6030, p=0.0001) and OS index (r=0.4298, p=0.012). Conclusion: The oxidative stress markers show good correlation with the tested cytokines which can be measured at the beginning of the disease in a primary care setting to predict the course of COVID-19.

Highlights

  • COVID-19 can be worsened by hyper-production of cytokines accompanied by increased level of oxidative stress

  • High levels of IL-6, IL-10, IL-2R and TNF-α have been reported in patients with severe form of the disease[13,14] other authors suggest that more cytokines, such IL-1β, IL-1RA, IL-8, IL-18 are included in the COVID-19 pathogenesis.[7,13,14]

  • We share our results to give an add-on to the clinical evidences that oxidative stress is increased in patients with severe form of COVID-19 and that the measured oxidative stress parameters had shown a good correlation with the cytokines and the commonly used laboratory biomarkers

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Summary

Introduction

COVID-19 can be worsened by hyper-production of cytokines accompanied by increased level of oxidative stress. Following influenza viral infection, an excessive amount of reactive oxygen species (ROS) is produced in several tissues including alveolar epithelium and endothelium[1] for which induced expression of cytokines through activation of Tolllike receptors (TLR3, TLR7 and TLR8, retinoic acid inducible gene I and members of NOD-like receptor family) stand in the background of the pathogenesis.[2,3] Oxidative stress is typical for infection of human respiratory syncytial virus,[4] rhinoviruses,[5] and many other viruses This has been discussed in previously published reviews[7,8,9,10,11,12] and as well, several experimental studies suggest that cytokine storm correlated with direct tissue injury and lead to unfavourable prognosis of severe form of the COVID-19 disease.[7] Briefly, high levels of IL-6, IL-10, IL-2R and TNF-α have been reported in patients with severe form of the disease[13,14] other authors suggest that more cytokines, such IL-1β, IL-1RA, IL-8, IL-18 are included in the COVID-19 pathogenesis.[7,13,14]

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