Elevated HDL may improve resistance to SARS-CoV-2 infection



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

Chidambaram does not report material financial disclosures.

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

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

HDL Blocks 2019
Source: Adobe Stock

“It was already hypothesized that patients with CVD, diabetes and hypertension are at increased risk of COVID-19 severity and mortality. And we already know that high LDL and low HDL cholesterol can lead to CVD. We wanted to see what effect lipid levels per se affect on COVID-19 outcomes,” Chidambaram told Healio. “Based on our initial systematic review, all these lipid levels dropped. We wanted to see if this was really the case. One association is that HDL is very important for inflammatory cells, especially macrophages and lymphocytes. We thought that HDL would be one of the important factors influencing the infection. We also thought that LDL could also lead to infection risk, but we found no direct association between LDL and COVID-19 outcomes. But when we did a subgroup analysis based on LDL and HDL, the subgroup with the highest LDL and the lowest HDL had the highest risk of infection.”

Citing the World Health Organization’s COVID-19 Panel, as of July 29, 2022, there were over 572 million confirmed cases of COVID-19, over 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 is influenced by LDL and HDL levels.

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

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

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

Therefore, Chidambaram and colleagues performed another analysis evaluating the association between low background lipids and increased risk of 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 illness at some point and of these, 16.1% died of COVID-19.

Chidambaram and colleagues noted that high levels of LDL (P = 0.331) and total cholesterol (P – .115) were not significantly linked to SARS-CoV-2 infection; however, low HDL was associated with risk of infection (P <.001).

“The most likely biological possibility is that patients with higher HDL – anywhere between 50 and 150 mg/dL – have a better inflammatory response and a lower risk of infection,” Chidambaram told Healio. “The infection was confirmed with PCR tests. If the patients weren’t adequately loaded… it could show a negative test. A negative test can mean that the infection is already under control before it is detected by a positive test. We think HDL acts as an immunomodulator and modifies inflammatory and immune responses and lowers the risk of infection.”

In other findings, the 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 may be no direct implications of this, but it opens up many avenues for future research,” Chidambaram told Healio. “If we can establish causality for this association, given that HDL is an important target for future preclinical studies… [to prevent or treat infection]. It hasn’t been studied before.

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


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