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

• DOI: 10.1016/j.jlr.2021.100061
• Publication Date: 2021-03-02T17:32:24Z
• 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
• Keywords: Male; 0301 basic medicine; Coronaviruses; Medical Biochemistry and Metabolomics; Cardiovascular; Biochemistry; apolipoprotein A1; 2.1 Biological and endogenous factors; Patient-oriented and Epidemiological Research; Lung; Metabolic Syndrome; 2. Zero hunger; Homozygote; Middle Aged; HDL-cholesterol; 3. Good health; Infectious Diseases; Cholesterol; Female; Adult; Biochemistry & Molecular Biology; SAR-CoV-2; HDL; 610; QD415-436; genetic risk score; metabolic syndrome; ApoE4; 03 medical and health sciences; 616; Genetics; Mendelian randomization; Medical biochemistry and metabolomics; Humans; Metabolic and endocrine; Nutrition; Aged; Biomedical and Clinical Sciences; Apolipoprotein A-I; SARS-CoV-2; genetic variants; Cholesterol, HDL; Patient Acuity; COVID-19; Atherosclerosis; United Kingdom; Good Health and Well Being; Emerging Infectious Diseases; Biochemistry and cell biology; Biochemistry and Cell Biology; Biomarkers

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.