Study of Albumin Oxidation in COVID-19 Pneumonia Patients: Possible Mechanisms and Consequences

Abstract

Oxidative stress induced by neutrophils and hypoxia in COVID-19 pneumonia leads to albumin modification. This may result in elevated levels of advanced oxidation protein products (AOPPs) and advanced lipoxidation end-products (ALEs) that trigger oxidative bursts of neutrophils and thus participate in cytokine storms, accelerating endothelial lung cell injury, leading to respiratory distress. In this study, sixty-six hospitalized COVID-19 patients with respiratory symptoms were studied. AOPPs-HSA was produced in vitro by treating human serum albumin (HSA) with chloramine T. The interaction of malondialdehyde with HSA was studied using time-resolved fluorescence spectroscopy. The findings revealed a significantly elevated level of AOPPs in COVID-19 pneumonia patients on admission to the hospital and one week later as long as they were in the acute phase of infection when compared with values recorded for the same patients 6- and 12-months post-infection. Significant negative correlations of albumin and positive correlations of AOPPs with, e.g., procalcitonin, D-dimers, lactate dehydrogenase, aspartate transaminase, and radiological scores of computed tomography (HRCT), were observed. The AOPPs/albumin ratio was found to be strongly correlated with D-dimers. We suggest that oxidized albumin could be involved in COVID-19 pathophysiology. Some possible clinical consequences of the modification of albumin are also discussed.

Direct Application of 3-Maleimido-PROXYL for Proving Hypoalbuminemia in Cases of SARS-CoV-2 Infection: The Potential Diagnostic Method of Determining Albumin Instability and Oxidized Protein Level in Severe COVID-19

“…High levels of OS suggest a high degree of protein oxidation, structural changes in the protein molecule, the formation of non-functional derivatives, and reduced antioxidant capacity of this critical protein in several COVID-19. Based on our results, we hypothesize that hypoalbuminemia is not only due to the inflammation associated with COVID-19 but rather to oxidative damage, which is also confirmed by other authors [ 51 , 56 ].…”

“…On the one hand, hyperinflammation in COVID-19 may lead to reduced albumin synthesis and hypoalbuminemia, on the other hand, low albumin levels may result from high clearance of damaged and oxidized albumin [ 56 ]. Based on the obtained CW-EPR data ( Figure 5 ), we hypothesize that in COVID-19 patients, high levels of ROS are the cause of albumin oxidation, the formation of biologically non-functional end products, and the loss of antioxidant activity.…”

Relationship between red blood cell aggregation and dextran molecular mass

“…It has been investigated that chlorine compounds produced by activated neutrophils in viral or bacterial infection lead to oxidative modification of albumin and the formation of AOPPs 57,58 . Indeed, the results of our previous study revealed that elevated level of AOPPs is associated with inflammation during the course of COVID-19-related pneumonia 59 . Interestingly, RBCs aggregation was also found to increase in patients with COVID-19 3 .…”

Site-Directed Spin Labeling EPR Spectroscopy for Determination of Albumin Structural Damage and Hypoalbuminemia in Critical COVID-19

“…The different sources of OS in COVID-19 include the generation of free radicals as a protective response to the entry of the virus into the body, an inflammatory response and a cytokine storm accompanied by the production of oxidants leading to the disruption of cellular structures [ 1 , 25 ] and irreversible protein oxidation [ 8 ]. The therapeutics used in the treatment of COVID-19 can exacerbate the pathogenesis of COVID-19, directly increase the risk of intoxication [ 28 ], and disrupt the normal redox balance in the body by mediating the formation of ROS/RNS [ 29 ].…”

“…In the acute phase of COVID-19, HAS acts as an antioxidant, but high levels of OS can lead to its irreversible oxidation [ 6 , 7 ]. Free radicals (ROS, RNS) are responsible for oxidative damage to HAS, oxidized albumin and low protein level have been implicated in the severity and mortality of patients with SARS-CoV-2 infection [ 8 ]. Badawy et al, reported that hydrogen peroxide and neutrophil-mediated OS induced protein structural and functional changes in patients with COVID-19 [ 9 ].…”