Possible mechanisms of cholesterol elevation aggravating COVID-19

Abstract

Importance: Despite the availability of a vaccine against the severe acute respiratory syndromecoronavirus-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.

Combinatorial influence of environmental temperature, obesity and cholesterol on SARS-CoV-2 infectivity

“…Though increased cholesterol levels promote ACE2 and furin trafficking inside host cells 21 , cholesterol plasma levels are found to be decreased in patients post-infection. In brief, high cholesterol present in host cell membrane, virus particles, and human blood may augment the virus entry processing in the host cells 21 , 23 . Our data depicted that geographic locations above 23.5 o N latitude and towards the poles had a higher prevalence of high average total cholesterol levels, often overlapping the areas with the highest COVID-19 cases (Fig.…”

“…Tang et. al reported the role of cholesterol in increasing the density of ACE2 receptors on host cell membranes 23 . Reports using super-resolution imaging have also observed increased SARS-CoV-2 entry in cells with high blood serum cholesterol levels 40 .…”

Hyperlipidemia, COVID-19 and acute pancreatitis: A tale of three entities

“…91 In addition, previous reviews suggested that patients with hypercholesterolemia had increased risk for COVID-19 and the related complications. 92 , 93 However, one study compared between two cohorts, namely COVID-19 patients discharged alive and those that died, and multiple regression analysis showed that hyperlipidemia had a protective effect on reducing the likelihood of death (OR=0.75). 94 Another study carried out cluster analysis in a large cohort of 12,066 COVID-19 patients, and the results showed that hyperlipidemia had no significant effects on COVID-19 prognosis.…”

Sleep and circadian rhythm disruption alters the lung transcriptome to predispose to viral infection

“…Furthermore, statins have been found to reduce recovery time and decrease the risk for COVID-19 morbidity and mortality 66,67 . How cholesterol impacts SARS-CoV-2 pathogenesis is currently unclear; however, lipid raft disruption, modification of membrane biophysics, alteration of viral stability and maturation, and immune dysfunction have all been suggested as potential mechanisms [68][69][70] .…”