Cholesterol and COVID-19

Years ago, I read a Japanese study on cholesterol that caused quite a stir in the lipid-research world. The study and the resulting change in cholesterol guidelines from the Japan Society for Lipid Nutrition demonstrated that higher total cholesterol and higher LDL cholesterol have protective effects that reduce all cause mortality. This finding upended the prior 50+ years of lipid research.

With COVID-19 cases spiking in many parts of the world, and a new and more dangerous strain may be spreading out in the wild, I recalled the Japanese research. So I queried professor Google to see if there has been any research connecting LDL cholesterol (the bad cholesterol) and HDL cholesterol (the good cholesterol). I quickly found two studies that had done retrospective analyses on hospital-admitted COVID patients.

1. Letter to the Editor: Low-density lipoprotein is a potential predictor of poor prognosis in patients with coronavirus disease 2019.

In surviving cases, the low-density lipoprotein (LDL) levels decreased significantly on admission as compared with the levels before infection; the LDL levels remained constantly low during the disease progression and resumed to the original levels when patients recovered. In non-surviving patients, LDL levels showed an irreversible and continuous decrease until death. The ratio changes of LDL levels inversely correlated with ratio changes of high-sensitivity C-reactive protein levels. Logistic regression analysis showed increasing odds of lowered LDL levels associated with disease progression and in-hospital death.

LDL levels inversely correlated to disease severities, which could be a predictor for disease progress and poor prognosis.

2. Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19.

Results A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8%. Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease with complete resolution among survivors. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl, C-reactive protein > 88 mg/dl and lymphopenia < 1,000 at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission.

Conclusion Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.

These studies both suggest that COVID-19 patients who have high LDL cholesterol prior to admission and those that maintain their LDL levels during progression of the disease have significantly better outcomes and significantly lower mortality as a result of COVID-19.

Both conclusions suggest that higher LDL cholesterol levels are indeed protective.