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Covid-19 and Cholesterol

With the COVID-19 pandemic, functional and integrative medicine providers have repeatedly spoken about the importance of cardiovascular risk factors when it comes to mortality and morbidity risk if infected. One of the main cardiovascular risk factors physicians use in practice is total cholesterol, usually including the more specific markers of high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides. Understanding how the SARS-CoV-2 virus interacts with the body’s cholesterol metabolism can help individuals understand their personal risk of infection and how an infection might affect their risk factors in the long term.

Cholesterol is complicated. Though generally given a bad rap, it does actually perform a number of essential functions, including making hormones, metabolizing fatty foods, and carrying lipid molecules around the body. The problem comes in when cholesterol levels get too high, whether genetic enzyme deficiencies or by poor dietary and lifestyle choices. However, it is really all about balance of the different subtypes. High-density lipoproteins (HDL), frequently regarded as the “good” cholesterol are associated with a lower risk of cardiovascular disease. Low-density lipoprotein (LDL), regarded as the “bad” cholesterol is associated with plaque build up, increasing the risk of cardiovascular events. The third main subtype, known as triglycerides, is a fat molecule that circulates in the blood, also associated with an increased risk of heart disease (1).

When it comes to COVID-19, there is more and more evidence that higher levels of HDL cholesterol is related to lower rates of severe infection. One prospective cohort study, using the UK Biobank, showed that an unfavorable pre-pandemic vascular risk factor profile, including low HDL, was associated with higher rates of hospitalization. In addition, higher levels of HDL were also associated with lower risk of hospitalization and morbidity, hypothesizing a stronger correlation (2). Though many additional factors could be related, such as higher cholesterol being tied to excessive weight and metabolic issues, which is therefore tied to higher overall morbidity and mortality; the question remains if the cholesterol itself could be more directly related to the viral process. Research is trying to figure that out.

One study discussing the relationship between cholesterol and SARS-CoV-2 reports that increased levels of cellular membrane cholesterol could actually facilitate viral entry into the cell. The research looking into this describes how the fusion proteins in the cell membrane of both the virus and host cell are dependent on cholesterol to perform this process. They even site a recent study that showed the spike protein on SARS-CoV-2 requires cholesterol in the host cell to engage (3). Therefore, it can be hypothesized that excess cholesterol, especially pro inflammatory cholesterol such as LDL, circulating in the human body could enhance the viruses’ ability to enter the host cells and cause infection.

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Anti-inflammatory cholesterol, such as HDL, may also have a more direct effect on viral function above just being associated with an overall higher level of baseline health. Studies have shown HDL particles can actually have an antiviral effect on RNA and DNA viruses, including the RNA virus causing COVID-19. It is thought that HDL has the ability to inactivate the virus, while also acting as an antioxidant, scavenging pathogenic materials and aiding in its removal from the body (4). This ultimately would both prevent infection and improve outcomes if an infection were to occur.

With these interactions between cholesterol and SARS-CoV-2, it leads to the question on if a treatment option can be elucidated from this relationship. Interestingly enough, a possible treatment option has been looked at with promising results. A systematic review and meta-analysis in 2021 confirmed that inpatient hospital use of statin therapy leads to a significant reduction in all-cause mortality in COVID-19 patients (5). It is thought that this benefit could be attributed to the ability of statins to reduce the inflammatory aspect of elevated LDL cholesterol, while possibly even increasing the beneficial HDL.

The COVID-19 pandemic has resulted in a significant amount of research within the medical community, especially regarding lifestyle and nutritional factors of patients. It is well known that those with heart and/or metabolic disease are at higher risk for severe disease and even death if infected. Therefore, when it comes to cholesterol, a potent marker of cardiovascular risk, it is no surprise that a relationship was found. What is surprising however is how cholesterol can have a more direct effect on viral entry into host cells and even against the virus itself. As time goes on, more about this will be understood. In the meantime, understanding ones own cardiovascular risk via at-home cholesterol panel offered by AYUMETRIX can help one understand how their health interplays with their susceptibility to a severe COVID-19 infection.

- Mary Hall, ND, LAc

References:

1. “About Cholesterol.” 2023. Centers for Disease Control and Prevention. https://www.cdc.gov/cholesterol/about.htm

2. Lassale, C., Hamer, M., Hernaez, A., Gale, C.R., Batty, G.D. 2021. Association of pre-pandemic high-density lipoprotein cholesterol with risk of COVID-19 hospitsation and death: the UK Biobank cohort study. medRxiv PrePrint. Online.

3. Tang, Y., Hu, L., Liu, Y., Zhou, B., Qin, X., Ye, J., Shen, M., Wu, Z., Zhang, P. 2021. Possible mechanisms of cholesterol elevation aggravating COVID-19. Int J Med Sci. 18(15): 3533-3543.

4. Kocar, E., Rezen, T., Rozman, D. 2021. Cholesterol, lipoproteins, and COVID-19: basic concepts and clinical applications. Biochim Biophys Acta Mol Cell Biol Lipids. 1866(2): 158849.

5. Vahedian=Azimi, A., Mohammadi, S.M., Benach, M., Beni, F.H., Guest, P.C., Al-Rasadi, K., Jamialahmadi, T., Sahebkar, A. 2021. Improved COVID-19 outcomes following statin therapy: an updated systematic review and meta analysis. Biomed Res Int. 1901772. Online.

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