SARS-CoV-2 induced HDL dysfunction may affect the host's response to and recovery from COVID-19

Abstract

Introduction: Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia, dysregulation of high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Furthermore, SARS-Co-2 infection is associated with noteworthy changes in lipid profile, which is suggested as a possible biomarker to support the diagnosis and management of Covid-19.

Methods: This paper adopts the literature review method to obtain information about how Covid-19 affects high-risk group patients and may cause severe and critical effects due to the development of acute lung injury and acute respiratory distress syndrome. A narrative and comprehensive review is presented.

Results: Reducing HDL in Covid-19 is connected to the disease severity and poor clinical outcomes, suggesting that high HDL serum levels could benefit Covid-19. SARS-CoV-2 binds HDL, and this complex is attached to the co-localized receptors, facilitating viral entry. Therefore, SARS-CoV-2 infection may induce the development of dysfunctional HDL through different mechanisms, including induction of inflammatory and oxidative stress with activation of inflammatory signaling pathways. In turn, the induction of dysfunctional HDL induces the activation of inflammatory signaling pathways and oxidative stress, increasing Covid-19 severity.

Conclusions: Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia in general and dysregulation of high-density lipoprotein and low-density lipoprotein. Therefore, the present study aimed to overview the causal relationship between dysfunctional high-density lipoprotein and Covid-19.

Keywords: Covid-19; SARS-CoV-2 infection; angiotensin-converting enzyme 2 (ACE2); cardio-metabolic disorders; dyslipidemia; high-density lipoprotein (HDL); low-density lipoprotein (LDL).

Figure 1

Angiotensin II (AngII) in Covid‐19: Angiotensin‐converting enzyme 2 (ACE2) as a receptor for entry for SARS‐Co‐2, downregulation of ACE2 causes over‐activation of the renin‐angiotensin system. ACE converts AngI to AngII, ACE2 converts AngII to Ang1‐7, which acts on the Mas receptor leading to protective effects. On the other hand, AngII through angiotensin type 1 receptor leads to harmful effects.

Figure 2

Structure of high‐density lipoprotein.

Figure 3

Metabolic pathway of high‐density lipoprotein (HDL): The biosynthesis of HDL started when ApoA1 acquired cholesterol and phospholipids in the circulation via ATP binding cassette transporter to form premature HDL particles. Through lecithin cholesterol acyltransferase, these particles maintain the accumulation of cholesterol and form a hydrophobic core with HDL particles. HDL takes more cholesterol in circulation and exchanges lipids with lipoproteins via cholesteryl ester transfer protein and phospholipids.

Figure 4

Pleiotropic effects of high‐density lipoprotein.

Figure 5

Anti‐inflammatory effects of high‐density lipoprotein (HDL): HDL inhibits expression of adhesion molecules and monocyte chemoattractant protein 1 (MCP‐1), reducing LDL oxidation and forming oxidized LDL. HDL attenuates the stimulatory effects of oxLDL on macrophages to release inflammatory cytokines.

Figure 6

Development of dysfunctional high‐density lipoprotein (HDL): Adipokines from adipocytes and physical activity improvement promote normal HDL. At the same time, risk factors for CAD may induce modification of composition and function of HDL, causing dysfunctional HDL due to modifications of ApoA1, paraoxonase‐1, and phospholipase.

Figure 7

Inflammation, oxidative stress, and development of dysfunctional high‐density lipoprotein (HDL): High oxidative due to reactive oxygen species and advanced glycation end product increase inflammation, which decrease paraoxonase‐1 and increase myeloperoxidase, causing dysfunctional HDL, which lost its cholesterol efflux capacity.

Figure 8

Immunological effects of high‐density lipoprotein.

Figure 9

The potential role of high‐density lipoprotein in SARS‐CoV‐2 infection.

Figure 10

Development of dysfunctional high‐density lipoprotein in SARS‐CoV‐2 infection.