Possible mechanisms of cholesterol elevation aggravating COVID-19

Area of Science:

• Biochemistry and Molecular Biology
• Virology
• Immunology

Background:

• Cholesterol plays a significant role in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and prognosis.
• Understanding cholesterol's mechanism is crucial for COVID-19 treatment and antiviral drug development.
• Cholesterol contributes to atherosclerosis via NLRP3 inflammasome activation, creating an inflammatory environment that exacerbates COVID-19.

Purpose of the Study:

• To elucidate the multifaceted role of cholesterol in SARS-CoV-2 infection and COVID-19 progression.
• To investigate cholesterol's involvement in viral entry mechanisms and its interaction with viral proteins.
• To assess the implications of cholesterol metabolism for COVID-19 patient management and lipid-lowering therapy.

Main Methods:

• Review of existing literature on cholesterol, SARS-CoV-2, and COVID-19.
• Analysis of in vitro studies examining cholesterol's effect on host cell membranes and viral entry.
• Examination of the role of scavenger receptor class B type 1 (SR-B1) in cholesterol-mediated viral entry.

Main Results:

• Cholesterol promotes atherosclerosis by activating NLRP3, indirectly worsening COVID-19.
• In vitro, membrane cholesterol increases viral entry sites and angiotensin-converting enzyme 2 (ACE2) receptor availability.
• SARS-CoV-2 spike protein interacts with cholesterol, facilitating host cell entry, with SR-B1 playing a key role.

Conclusions:

• Cholesterol increases SARS-CoV-2 susceptibility and mortality risk through NLRP3 and atherosclerotic plaques.
• Cholesterol may directly facilitate viral entry via host cell membranes, viral particles, and blood, requiring further mechanistic study.
• Continuation of lipid-lowering therapy is advised for COVID-19 patients, with caution regarding extremely low LDL-C.