Elevated HDL may improve SARS-CoV-2 infection resistance



Chidambaram V. 1st Place EC Research Winner. Presented at: American Society for Preventive Cardiology Congress on CVD Prevention; July 29-31, 2022; Louisville, Kentucky.

Chidambaram reports no relevant financial disclosures.

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LOUISVILLE, Ky. — Changes in HDL level may be linked with SARS-CoV-2 infection risk and subsequent outcomes in COVID-19, a speaker reported.

Vignesh Chidambaram, MD MPHinternal medicine resident in the laboratory of Jawahar L. MehtaMD, PhD, Stebbins Chair and professor of medicine at the college of medicine at the University of Arkansas for Medical Sciences, won the first-place early career research award at the American Society for Preventive Cardiology Congress on CVD Prevention for evaluating the association between antecedent lipid levels and risk for SARS-CoV-2 infection.

HDL blocks 2019
Source: Adobe Stock

“There was already a hypothesis that patients with CVD, diabetes and hypertension have higher risk for COVID-19 severity and mortality. And we already know that high LDL cholesterol and low HDL can lead to CVD. We wanted to see what effect lipid levels per se impact COVID-19 outcomes,” Chidambaram told Healio. “Based on our initial systematic review, all of these lipid levels came down. We wanted to see if that was actually the case. One association is that HDL is very important for the inflammatory cells, especially macrophages and lymphocytes. We thought HDL was going to be one of the important influencing factors in infection. We also thought LDL could also lead to risk for infection, but we did not find any direct association between LDL and COVID-19 outcomes. But when we did a subgroup analysis based on the LDL and HDL, the subgroup with the highest LDL and the lowest HDL had the highest risk for infection.”

Citing the World Health Organization COVID-19 Dashboard, as of July 29, 2022, there have been more than 572 million confirmed cases of COVID-19, more than 6.3 million deaths and, as of July 26, 2022, more than 12 billion vaccine doses administered.

Chidambaram explained that CVD, diabetes and hypertension are associated with poor outcomes in COVID-19, and each of these risk factors are influenced by levels of LDL and HDL.


Therefore, Chidambaram said, cholesterol within a host’s cell membrane may play an important role in SARS-CoV-2 infection due to the constant interaction of LDL and HDL with lipid rafts in these cell membranes.

In a study published in 2022 in Frontiers in Cardiovascular MedicineChidambaram and colleagues evaluated whether lipid levels were associated with SARS-CoV-2 infection, COVID-19 severity and mortality.

They observed that adjustment for age, sex, diabetes, hypertension or presence of CAD did not attenuate the association between lipid levels and SARS-CoV-2 infection, COVID-19 severity and mortality; however, Chidambaram stated that their findings suffered from potential reverse causality due to the acute inflammatory response in COVID-19.

Therefore, Chidambaram and colleagues conducted another analysis evaluating the association between low antecedent lipids and increased risk for SARS-CoV-2 infection.

The patient cohort consisted of 1,340 individuals who tested positive for COVID-19, of which 27.3% required hospitalization. Among patients who required hospitalization, 28.9% had severe disease at any time and of them, 16.1% died of COVID-19.

Chidambaram and colleagues noted that elevated LDL (P = .331) and total cholesterol (P – .115) were not significantly linked with SARS-CoV-2 infection; however, low HDL was associated with risk for infection (P < .001).

“The most likely biological possibility is that patients with higher HDL — anywhere between 50 and 150 mg/dL — had better inflammatory response and lower risk for infection,” Chidambaram told Healio. “The infection was confirmed with PCR testing. If patients did not have adequate load … it might show a negative test. A negative test may mean that the infection is already controlled before it being detected by a positive test. We think that HDL acts as an immunomodulator and modifies the inflammatory and the immune responses and decreases the risk for infection.”

In other findings, researchers observed that HDL decreased during SARS-CoV-2 infection and returned to pre-infection levels 60 days after infection, while total cholesterol was unaffected during SARS-CoV-2 infection.

“There might not be any direct implication right from this, but it opens up a lot of avenues for future research,” Chidambaram told Healio. “If are able to establish the causality for this association, seeing that HDL is an important target for future preclinical studies … we can actually use HDL increasing agents [to prevent or treat infection]. It’s not been studied before.

“It could be more than COVID-19; it may be useful for infections in general, and there are a lot of clinical data on how statins are being used in tuberculosis, HIV and these chronic infections as an add-on agent but may not be directly useful as a monotherapy,” Chidambaram told Healio. “If they add on to HIV medication, tuberculosis medication or maybe other medications, they can maybe potentiate the effects of these medications and maybe reduce the duration of treatment, or maybe reduce the dose. HIV medications have a lot of side effects. Maybe if they add on a particular statin, they’re able to reduce the dose of those other medications. That being said, it still needs to be proven and still needs to go through clinical trials. That could be an exciting avenue to explore in the future.”



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