Cholesterol Acts as Hidden Doorway for COVID-19 Virus Entry

Cholesterol regulates the viral infectivity of the COVID-19 virus through the localization of its receptors angiotensinogen converting enzyme 2 (ACE2) into lipid clusters, according to a new study published in Journal of Biological Chemistry.

COVID-19 is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus binds to ACE2, which mediates viral entry into cells. ACE2 is like a doorknob; when SARS-CoV-2 grabs it and maneuvers it precisely, this allows the virus to open a doorway to the cell’s interworking and step inside. However, the identity of the door eluded scientists.

Role of High Cholesterol in COVID-19 Severity

Early in the COVID-19 pandemic, the elderly and people with chronic diseases such as hypertension, diabetes, Alzheimer’s, and cardiovascular diseases experienced more viral-related deaths. However, children seemed to be less susceptible.

Coronavirus
Coronaviruses infect animals, humans, and birds. Human coronaviruses, such as SARS, MERS, and 2019-nCoV cause respiratory distress and even death. The S protein is the infectious agent of the virus.

‘Cholesterol level in blood increases viral infectivity and may help explain the selective severity of COVID-19 in aged and diseased populations. #cholesterol #COVID-19 #SARS-CoV-2’

Tweet it Now

Researchers hypothesized that part of this phenomenon was due to the high amounts of tissue cholesterol in populations with chronic disease. From 2017 to 2020, 86.4 million U.S. adults aged 20 or older had high or borderline high cholesterol in their blood.

After completing studies using new technology like super-resolution microscopy, they showed that cholesterol on the cell surface makes ACE2 readily accessible to SARS-CoV2 for cell entry.

Cholesterol is part of a place where nutrients come into the cell (). It is necessary for survival, but too much cholesterol may be increasing your risk for COVID-19 at the cellular and biochemical levels.

Post-COVID Syndrome
Post-COVID complications are the conditions that develop weeks after recovering from COVID-19

In smokers with chronic disease, cholesterol in the lung tissue is elevated two-fold, a magnitude of change that dramatically increases the infectivity of the virus in cell culture.

In fact, according to a study, supported by the National Heart, Lung, and Blood Institute, smoking was associated with a higher risk of severe COVID-19, including death. However, past research has shown that the cholesterol-promoting SARS-CoV-2 infection can easily be disrupted to help patients stay healthy and avoid infection ().

Exercise Regularly to Avoid COVID-19 Complications

Mechanical force and polyunsaturated fatty acids disrupt the aggregation of cholesterol. Healthy mechanical force is achieved with exercise. In our studies, cells need to be jostled a little bit to keep the cholesterol from setting up in the cell membrane.

COVID-19 Increased Psychological Distress Among UK University Students
The pandemic has had a profound impact on UK undergraduates' mental health, as they experienced prolonged distress and reduced well-being.

Regular exercise with its increased heart rate and blood flow should reduce the cholesterol aggregates in the cell membranes. In addition to new insights on the entry mechanism of SARS-CoV-2, this study also highlighted the inaccuracies of the way doctors assess cholesterol risk in their patients.

Currently, the only way to test cholesterol levels is via a blood test. If you measure cholesterol levels in the blood, you do not know the levels in the tissue or if it is being taken out or brought in. Hence, researchers are working with physicians to come up with a test that more accurately represents tissue cholesterol and its distribution throughout the body.

Why Does COVID-19 Affect Different People Differently?
The reason why different people are affected by COVID-19 differently could lie in their genetic makeup.

Instead of focusing on the blood, which changes every time you eat, they will need to focus on the tissues and how the cholesterol is taken up over time (). It is a harder measurement, but, in the end, it may help people understand their risk for disease and save lives.

References:

Coronavirus Infection and Cholesterol Metabolism - (https://www.frontiersin.org/articles/10.3389/fimmu.2022.791267/full)
The role of high cholesterol in SARS-CoV-2 infectivity - (https://www.jbc.org/article/S0021-9258(23)01791-X/fulltext#secsectitle0045)
The effects of exercise training on lipid metabolism and coronary heart disease - (https://journals.physiology.org/doi/full/10.1152/ajpheart.00708.2019)

Source-Eurekalert