Association of serum HDL-cholesterol and apolipoprotein A1 levels with risk of severe SARS-CoV-2 infection.

Abstract

Individuals with features of metabolic syndrome are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus associated with the severe respiratory disease, coronavirus disease 2019 (COVID-19). Despite considerable attention dedicated to COVID-19, the link between metabolic syndrome and SARS-CoV-2 infection remains unclear. Using data from the UK Biobank, we investigated the relationship between severity of COVID-19 and metabolic syndrome-related serum biomarkers measured prior to SARS-CoV-2 infection. Logistic regression analyses were used to test biomarker levels and biomarker-associated genetic variants with SARS-CoV-2-related outcomes. Among SARS-CoV-2-positive cases and negative controls, a 10 mg/dl increase in serum HDL-cholesterol or apolipoprotein A1 levels was associated with ∼10% reduced risk of SARS-CoV-2 infection, after adjustment for age, sex, obesity, hypertension, type 2 diabetes, and coronary artery disease. Evaluation of known genetic variants for HDL-cholesterol revealed that individuals homozygous for apolipoprotein E4 alleles had ∼2- to 3-fold higher risk of SARS-CoV-2 infection or mortality from COVID-19 compared with apolipoprotein E3 homozygotes, even after adjustment for HDL-cholesterol levels. However, cumulative effects of all evaluated HDL-cholesterol-raising alleles and Mendelian randomization analyses did not reveal association of genetically higher HDL-cholesterol levels with decreased risk of SARS-CoV-2 infection. These results implicate serum HDL-cholesterol and apolipoprotein A1 levels measured prior to SAR-CoV-2 exposure as clinical risk factors for severe COVID-19 infection but do not provide evidence that genetically elevated HDL-cholesterol levels are associated with SAR-CoV-2 infection.

• Authors: James R Hilser, Yi Han, Subarna Biswas, Janet Gukasyan, Zhiheng Cai, Ruowei Zhu, W H Wilson Tang, Arjun Deb, Aldons J Lusis, Jaana A Hartiala, Hooman Allayee
• Journal: Journal of lipid research (J Lipid Res) Vol. 62 Pg. 100061 ( 2021) ISSN: 1539-7262 [Electronic] United States
• PMID: 33667465 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Apolipoprotein A-I
• Biomarkers
• Cholesterol, HDL

Topics

• Adult
• Aged
• Apolipoprotein A-I (blood, genetics)
• Biomarkers (blood)
• COVID-19 (blood, genetics, mortality)
• Cholesterol, HDL (blood, genetics)
• Female
• Homozygote
• Humans
• Male
• Metabolic Syndrome (blood, genetics, mortality)
• Middle Aged
• Patient Acuity
• SARS-CoV-2 (metabolism)
• United Kingdom (epidemiology)