Glycosylation Variability of Serum α1-Acid Glycoprotein in the Context of Developing Inflammation and Oxidative Stress in Patients with Severe COVID-19

In COVID-19 (coronavirus disease 2019), multi-organ complications depend on the immune system's activity. α1-Acid glycoprotein (AGP) is a highly glycosylated positive acute-phase protein having multifaceted immunomodulatory and protective effects. We were interested in changes in serum AGP concentrations, expression of its glycans, and oxidation-reduction potential (ORP) between severe COVID-19 patients, convalescents, and healthy controls, and whether any of the analyzed parameters could serve as an additional diagnostic biomarker of severe COVID-19 and/or help monitor recovery. We were also interested in associations between the examined parameters. AGP concentrations were measured using an immunoturbidimetric method. The profile and degree of AGP glycosylation were analyzed using lectin-ELISA with lectins: sialo-specific from <i>Sambucus nigra</i> (SNA) and <i>Maackia amurensis</i> (MAA), fucose-specific from <i>Lotus tetragonolobus</i> (LTA) and <i>Aleuria aurantia</i> (AAL). The static and capacitive ORP (sORP and cORP, respectively) were measured using MiOXSYS C+^® device (Caerus Biotechnologies, Vilnius, Lithuania). Statistica13.3PL software was used for statistical analysis. AGP concentrations increased in COVID-19 patients, showing high clinical usefulness in distinguishing them from convalescents and controls. AGP α2,6-sialylation (reactivity with SNA) was reduced in COVID-19 vs. other study groups, while α2,3-sialylation (reactivity with MAA) was reduced in convalescents vs. controls. The expression of LTA-reactive fucose (Lewis^x structures, Le^x) was reduced in COVID-19 patients compared to controls and convalescents, but AGP reactivity with AAL did not differ between the study groups. The sORP was reduced, and the cORP was increased in COVID-19. The observed negative correlations between sORP and AGP levels may suggest the antioxidant effect of AGP during severe COVID-19. Higher levels of serum AGP in severe COVID-19, together with low expression of sialic acid α2,6-linked and Le^x structures, accompanied by reduced sORP, constitute a characteristic pattern of biomarker expression during severe COVID-19. The increased expression of SNA-reactive sialic acid and Le^x structures may reflect the recovery process after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. The observed negative correlations between AGP and sORP levels may suggest that serum AGP in COVID-19 also plays a role as an antioxidative molecule.