COVID-19 News: SARS-CoV-2 Infections Lead To Buildup Of Oxysterols In Erythrocytes Which Can Be Used As A Biomarker For Disease Severity
: A new study by Saudi scientist from King Abdulaziz University and King Abdulaziz University Hospital has found that SARS-CoV-2 infections lead to the buildup of oxysterols in erythrocytes and also the accumulation of acylcarnitines, both of which can be toxic and damaging to the host cells, contributing to disease severity.
Oxysterols are the oxidation products of cholesterol. Oxysterols have an important role in the biological process of cholesterol homeostasis, apoptosis, and autophagy lipid metabolism. The blood level of oxysterol may be considered a diagnostic biomarker for specific diseases or prediction of the incidence of certain diseases, such as multiple sclerosis, osteoporosis, Alzheimer's disease, psychomotor diseases, and cancer.
Thailand Medical News had previously covered in brief the role of oxysterol and also long chain acylcarnitines in SARS-CoV-2 infections in past COVID-19 News
As a result of the high risk of COVID-19 patients to the formation of thrombosis in the circulating blood, atherosclerosis, and myocardial infarction, it was necessary to study the lipidomic of the erythrocytes.
The study team’s aim was to analyze the pathogenic oxysterols and acylcarnitines in the erythrocyte’s homogenate of COVID-19 patients and to estimate the case severity from the level of oxysterols.
A linear ion trap mass spectrometry coupled with high-performance liquid chromatography was used to investigate the extract of erythrocytes homogenate. The toxic biomarkers that primarily induce the generation of dead red blood cells, were characterized, and quantified in the erythrocytes of COVID-19 patients and matched with healthy volunteers.
In all a total of 30 patients and 30 healthy volunteers were enrolled.
The study findings showed that the concentration of five oxysterols and six acylcarnitines in the erythrocyte’s homogenate of COVID-19 patients was significantly upregulated matching with healthy subjects at p <0.05. The average total concentration of oxysterols was 23.36 ± 13.47 μg/mL in the erythrocytes of COVID-19 patients, while samples of healthy volunteers showed a total concentration of 4.92 ± 1.61 μg/mL.
Importantly, the average concentration level of 7-ketocholesterol and 4-cholestenone in the COVID-19 patients was higher by five a
nd ten-fold compared to the healthy subjects.
Furthermore, the average concentration of acylcarnitines in the erythrocyte's homogenate of COVID-19 patients was high by 2-to-4-fold in comparison with the healthy volunteers.
The abnormally high levels of oxysterols and acylcarnitines found in the erythrocytes of COVID-19 patients were associated with the severity of the case's complications and substantial risk of thrombosis.
Hence, the concentration of oxysterols in the erythrocyte homogenate could be useful as a diagnostic biomarker to stand on the COVID-19 case severity.
The study findings were published on a preprints server and is currently being peer reviewed for publication in the journal: BMC Respiratory Research.
It should be noted that it is already well known that the accumulation of oxysterols as an end product of cholesterol results in chronic pathogenesis accompanied by cellular damage, as in neurodegenerative disease, congestive heart failure, and acute viral infections.
Certain oxysterols exert potent oxidation damage to cells and acute inflammatory effects at low concentrations detected in the lesions of atherosclerosis, acute coronary syndrome, and neurodegenerative diseases. This atherosclerosis is due to oxidized lipids and cholesterol.
Past studies tested the antiviral effect of some oxysterols against COVID-19 activity using a cell-culture assay module. These studies reported that 7-ketocholesterol (7-KCh) inhibits the propagation of SARS-CoV-2 in culture cells.
Alarmingly however, 7-KCh exerts a toxic effect and induces cell damage. Because of these different toxic activities, 7-KCh has been claimed to contribute to the pathogenesis of COVID-19.
Hence, it has been postulated that the assay level of 7-KCh in plasma could be used as a prognostic biomarker for identifying the severity of COVID-19. This information could help identify patients at risk of worse clinical outcomes and optimize their medical care, thus perhaps decreasing the number of patients needing mechanical ventilation.
Importantly, in severe cases of COVID-19 infection, it has been hypothesized that 7-KCh could be a biomarker predicting the disease severity and its potential complications. It has been reported that the lipidomic analysis of erythrocytes collected from heart failure patients revealed oxysterols accumulation. Also, patients with high 7-KCh in plasma have shown extraordinarily more giant dead cells that make the plaques harder.
Already, it has been reported that both 7-ketocholesterol and 7β-cholesterol are moderately increased in the serum of COVID-19 patients using gas chromatography-mass spectrometry as an assay method.
Also, acylcarnitine translocase existed in extracellular and auto-activated to transport the long-chain fatty acids into mitochondria for β-oxidation used by the cells as an energy source.
It has been found that abnormal expression of some acyl-Co enzyme-A leads to the accumulation of some acyl-carnitines, which results in a toxic effect on the cell.
Also, important changes in acylcarnitine metabolism have been found in diseases such as dementia, heart failure, and coronary artery disease.
A past study demonstrated that COVID-19-infected patients had high concentrations of eighteen acylcarnitines in the plasma.
That study showed that mitochondria secreted more elevated levels of acylcarnitines, characterized by long-chain fatty acids, which could exhibit a high-risk factor for lung injury with uncontrolled oxidation of the fatty acid. The accumulated lipids in the air fluid could increase the infection severity.
Acylcarnitine accumulation may lead to toxicity due to the amphiphilic long-chain acylcarnitine, which has been demonstrated to inhibit ion channels, disrupt calcium signaling, and impair adenosine-triphosphate.
The current study findings are consistent with a past study that described that COVID-19 virus considered the human erythrocytes as a preferred target’s host for multiplication and cell damage.
From the study findings, it could be concluded that 7-KCh, specifically, increased significantly in both erythrocyte homogenate and serum.
Importantly, severe COVID-19 cases showed a higher level of the acylcarnitine C18:1_CARN. Also, COVID-19 patients showed a significantly higher concentration level of oxysterol which expresses the oxidative stress and, subsequently, the risk of apoptosis.
Though the mechanism of hypercoagulation has not been understood, it has been reported that oxysterols are toxic and pathogenic.
From the study findings, it could be concluded that COVID-19 patients are at a very high risk of thrombosis in the circulating blood, atherosclerosis, myocardial infarction, and pulmonary failure due to the lipidomic dysregulation of the erythrocytes-lipid composition.
Also, patients with COVID-19 infection showed that the erythrocyte’s homogenate contains a significantly high concentration of 7-ketocholesterol, 4-cholestenone, and six acylcarnitines.
All these lipidomes are very harmful to biological cells, namely red blood cells, and lead to thrombosis formation.
The study team said that it is highly advised to urgently prescribe antiplatelet drugs (aspirin, clopidogrel) to COVID-19 patients.
Also, as a biomarker, the concentration range of 7-ketocholesterol and 4-cholestenone in the erythrocytes of COVID-19 patients defined as severe was 52.0 to 16.6 and 4.5 to 1.5 µg/mL, respectively. However, the moderate COVID-19 cases showed a concentration range of 16.2 to 5.7 and 1.4 to 0.3 µg/mL for 7-KCh and 4-Ch, respectively.
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