Diversified Effects of COVID-19 as a Consequence of the Differential Metabolism of Phospholipids and Lipid Peroxidation Evaluated in the Plasma of Survivors and Deceased Patients upon Admission to the Hospital

Abstract

As a result of SARS-CoV-2 infection, inflammation develops, which promotes oxidative stress, leading to modification of phospholipid metabolism. Therefore, the aim of this study is to compare the effects of COVID-19 on the levels of phospholipid and free polyunsaturated fatty acids (PUFAs) and their metabolites produced in response to reactions with reactive oxygen species (ROS) and enzymes (cyclooxygenases-(COXs) and lipoxygenase-(LOX)) in the plasma of patients who either recovered or passed away within a week of hospitalization. In the plasma of COVID-19 patients, especially of the survivors, the actions of ROS and phospholipase A2 (PLA2) cause a decrease in phospholipid fatty acids level and an increase in free fatty acids (especially arachidonic acid) despite increased COXs and LOX activity. This is accompanied by an increased level in lipid peroxidation products (malondialdehyde and 8-isoprostaglandin F2α) and lipid mediators generated by enzymes. There is also an increase in eicosanoids, both pro-inflammatory as follows: thromboxane B2 and prostaglandin E2, and anti-inflammatory as follows: 15-deoxy-Δ-12,14-prostaglandin J2 and 12-hydroxyeicosatetraenoic acid, as well as endocannabinoids (anandamide-(AEA) and 2-arachidonylglycerol-(2-AG)) observed in the plasma of patients who recovered. Moreover, the expression of tumor necrosis factor α and interleukins (IL-6 and IL-10) is increased in patients who recovered. However, in the group of patients who died, elevated levels of N-oleoylethanolamine and N-palmitoylethanolamine are found. Since lipid mediators may have different functions depending on the onset of pathophysiological processes, a stronger pro-inflammatory response in patients who have recovered may be the result of the defensive response to SARS-CoV-2 in survivors associated with specific changes in the phospholipid metabolism, which could also be considered a prognostic factor.

The impact of COVID-19 on vitamin E concentrations and oxidative stress markers in adult subjects: A systematic review

“…This may justify the negative correlation trend found between tocopherol with ROOH and LDLox in the study by Pincemail, et al 17 , that is, the lower concentration of vitamin E occurs in parallel with higher concentrations of oxidized LDL and organic peroxides. This indicates the development of the lipid peroxidation process and that the increased action of reactive oxygen species in the patient with COVID-19 results in major changes in phospholipid metabolism and free fatty acids 25 .…”

Short Survey on the Protein Modifications in Plasma during SARS-CoV-2 Infection

“…The rate of increase of these molecules determines whether cells will survive by activating their antioxidant system or whether they induce mutation or apoptosis [ 39 ]. In the plasma of COVID-19 patients, a strong increase in the activity of enzymes responsible for lipid metabolism, such as phospholipase A2, is one of the factors explaining the increase in lipid peroxidation products, including the aforementioned reactive aldehydes [ 5 ]. As a result, both 4-HNE and MDA can directly interact with proteins, altering their structure and function.…”

“…Some of the PGJ2, including 15d-PGJ2, have anti-inflammatory and antiviral effects, which is being attempted to be used in COVID-19 therapies [ 53 ]. This may be due to the fact that a significant increase in 15d-PGJ2 levels is observed in the plasma of patients with mild COVID-19, whereas no such observation has been made in severe COVID-19 patients who consequently do not survive SARS-CoV-2 infection [ 5 ]. The results obtained in this study confirm this, as the amount of 15d-PGJ2-modified proteins is highest in COVID-19 survivors, whereas in deceased COVID-19 patients, the amount of 15d-PGJ2-modified proteins is decreased.…”

“…Plasma samples were collected upon admission to the hospital from a group of 10 COVID-19 survivors (6 females and 4 males) with a mean age of 62 (54–70) years and from 10 later-deceased patients with COVID-19 (6 females and 4 males) with a mean age of 68 (62–77) years who were treated during the period December 2020 to February 2022 at the Clinical Hospital Dubrava in Zagreb, which served as a national COVID-19 center. Patients were randomly selected from a group of 66 (COVID-19 survivors) and 22 (COVID-19 deceased) patients, whose results of classical analysis have previously been published [ 4 , 5 ]. The number of patients in each group was selected as 10 to provide convergent apparatus conditions to all injections and to ensure high-statistical-power analysis [ 60 ].…”

“…Previously, it has been described that the development of COVID-19 is also accompanied with a significant disturbance of redox homeostasis resulting in a high level of oxidative stress that is related to the severity of the damage caused by the infection [ 4 , 5 ]. The decrease in the activity of antioxidant enzymes (superoxide dismutases 1 and 2) and the decrease in the amount of low-molecular-weight antioxidants (glutathione, vitamins A and E) observed in the patient’s plasma [ 4 ] also favors pro-oxidant metabolism in the patient’s body.…”