High-density lipoproteins and COVID-19: preparing the next pandemic

Abstract

High-density lipoproteins (HDLs) are heterogeneous particles with pleiotropic functions including anti-inflammatory and anti-infectious effects. In clinical studies, lower HDL-associated cholesterol (HDL-C) concentration has been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and mortality. A reduction in the number of HDL particles, particularly small ones has been observed with alterations in their protein and lipid composition impairing their functions. These observations have supported HDL supplementation with promising results in small preliminary studies. This review summarizes available evidence to better understand the two-way interaction between HDLs and Coronavirus disease 2019 (COVID-19) and guide future HDL-based therapies for preparing for the next pandemic.

Keywords: COVID-19; drug therapy; dyslipidemia; epidemiology; high-density lipoproteins; inflammation; lipidomics; lipids; proteomics; reconstituted HDLs.

Fig. 1

Structural and functional changes in HDL under COVID-19 conditions and HDL mimetic supplementation. Under normal conditions, HDL (high-density lipoprotein) not only plays a role in cholesterol transport but also possesses anti-inflammatory and antioxidant properties. However, following infection with SARS-CoV-2, there is a noticeable decline in HDL levels, along with significant structural alterations. Key proteins such as apo A1 and apo M are reduced, while proinflammatory proteins such as SAA increase. Additionally, the lipid composition of HDL is affected, with decreases in cholesterol and phospholipids. These changes impair HDL's functionality. HDL mimetic supplementation has shown promising results in clinical cases, highlighting the importance of optimizing their composition and delivery methods to better target specific diseases.