Possible mechanisms of cholesterol elevation aggravating COVID-19

Int J Med Sci. 2021 Aug 21;18(15):3533-3543. doi: 10.7150/ijms.62021. eCollection 2021.

Abstract

Importance: Despite the availability of a vaccine against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), humans will have to live with this virus and the after-effects of the coronavirus disease 2019 (COVID-19) infection for a long time. Cholesterol plays an important role in the infection and prognosis of SARS-CoV-2, and the study of its mechanism is of great significance not only for the treatment of COVID-19 but also for research on generic antiviral drugs. Observations: Cholesterol promotes the development of atherosclerosis by activating NLR family pyrin domain containing 3 (NLRP3), and the resulting inflammatory environment indirectly contributes to COVID-19 infection and subsequent deterioration. In in vitro studies, membrane cholesterol increased the number of viral entry sites on the host cell membrane and the number of angiotensin-converting enzyme 2 (ACE2) receptors in the membrane fusion site. Previous studies have shown that the fusion protein of the virus interacts with cholesterol, and the spike protein of SARS-CoV-2 also requires cholesterol to enter the host cells. Cholesterol in blood interacts with the spike protein to promote the entry of spike cells, wherein the scavenger receptor class B type 1 (SR-B1) plays an important role. Because of the cardiovascular protective effects of lipid-lowering therapy and the additional anti-inflammatory effects of lipid-lowering drugs, it is currently recommended to continue lipid-lowering therapy for patients with COVID-19, but the safety of extremely low LDL-C is questionable. Conclusions and Relevance: Cholesterol can indirectly increase the susceptibility of patients to SARS-CoV-2 and increase the risk of death from COVID-19, which are mediated by NLRP3 and atherosclerotic plaques, respectively. Cholesterol present in the host cell membrane, virus, and blood may also directly participate in the virus cell entry process, but the specific mechanism still needs further study. Patients with COVID-19 are recommended to continue lipid-lowering therapy.

Keywords: COVID-19; LDL-C; cholesterol; lipid-lowering drugs; membrane fusion.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism
  • Antiviral Agents / therapeutic use
  • Atherosclerosis / physiopathology
  • COVID-19 / complications*
  • COVID-19 / diagnosis
  • COVID-19 / therapy
  • COVID-19 Drug Treatment
  • Cell Membrane / metabolism
  • Cholesterol, HDL / metabolism
  • Cholesterol, LDL / metabolism
  • Endocytosis
  • Humans
  • Hypercholesterolemia / complications*
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / therapy
  • Inflammation
  • Macrophages / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / blood
  • Prognosis
  • SARS-CoV-2
  • Scavenger Receptors, Class B / metabolism

Substances

  • Antiviral Agents
  • Cholesterol, HDL
  • Cholesterol, LDL
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2