Blood lipids after COVID-19 infection

Atherosclerotic cardiovascular disease incidence is increased both during acute COVID-19 infection and for an indefinite period afterwards.1Xie Y Xu E Bowe B Al-Aly Z Long-term cardiovascular outcomes of COVID-19.Nat Med. 2022; 28: 583-590Crossref PubMed Scopus (264) Google Scholar, 2Iqbal Z Ho JH Adam S et al.Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: an expert panel position statement from HEART UK.Atherosclerosis. 2020; 313: 126-136Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar For this reason it has been recommended that lipid-lowering medication is generally continued throughout the period of active infection and subsequently.2Iqbal Z Ho JH Adam S et al.Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: an expert panel position statement from HEART UK.Atherosclerosis. 2020; 313: 126-136Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar In this issue of The Lancet Diabetes & Endocrinology, Evan Xu and colleagues3Xu E Xie Y Al-Aly Z Risks and burdens of incident dyslipidaemia in long COVID: a cohort study.Lancet Diabetes Endocrinol. 2023; (published online Jan 6.)https://doi.org/10.1016/S2213-8587(22)00355-2Google Scholar provide evidence that this advice should go further. From a large observational study using participants from the US Department of Veterans Affairs database, they assessed the risks and burdens of incident dyslipidaemia in the post-acute phase of SARS-CoV-2 infection using 51 919 COVID-positive participants compared with two COVID-negative control groups. The authors found increased LDL cholesterol, triglycerides, total cholesterol, and decreased HDL cholesterol in survivors of COVID-19 compared with controls who had never had a positive COVID test. The degree of dyslipidaemia was greatest in those in whom the infection had been most severe and had required admission to intensive care. The authors adjusted the data to allow for confounding factors. Nevertheless, questions remain about whether the adverse post-COVID effect on dyslipidaemia is directly caused by the infection itself or indirectly by behavioural factors operating during the recovery period, such as reduced physical activity due to post-viral lethargy and persistent loss of exercise capacity, or dietary indulgence following the return of taste or the jubilation of survival. Greater certainty about their conclusions could be provided by a longitudinal study, which might, for example, be possible if lipids were measured in participants in a controlled vaccine trial. However, whatever the reason for the post-COVID dyslipidaemia, the immediate clinical message is the same: blood lipids should be checked as part of cardiovascular risk evaluation after recovery and, if necessary, lipid-lowering medication initiated or intensified. The report by Xu and colleagues3Xu E Xie Y Al-Aly Z Risks and burdens of incident dyslipidaemia in long COVID: a cohort study.Lancet Diabetes Endocrinol. 2023; (published online Jan 6.)https://doi.org/10.1016/S2213-8587(22)00355-2Google Scholar raises fundamental questions about the origins of dyslipidaemia in general. We know that the acute effect of infection or serious illnesses from other causes is to lower LDL cholesterol, sometimes profoundly.4Soran H Ho JH Durrington PN Acquired low cholesterol: diagnosis and relevance to safety of low LDL therapeutic targets.Curr Opin Lipidol. 2018; 29: 318-326Crossref PubMed Scopus (0) Google Scholar, 5Feingold KR Grunfeld C The Effect of inflammation and infection on lipids and lipoproteins.in: Feingold KR Anawalt B Boyce A Endotext. MDText.com, South Dartmouth, MA2000Google Scholar At the same time there is a tendency for triglycerides to rise and for HDL cholesterol to decrease. LDL cholesterol is usually restored to premorbid concentrations as the acute illness abates, but in chronic inflammation the increase in triglyceride and decreased HDL persists probably due to the effect of inflammatory cytokines.4Soran H Ho JH Durrington PN Acquired low cholesterol: diagnosis and relevance to safety of low LDL therapeutic targets.Curr Opin Lipidol. 2018; 29: 318-326Crossref PubMed Scopus (0) Google Scholar, 5Feingold KR Grunfeld C The Effect of inflammation and infection on lipids and lipoproteins.in: Feingold KR Anawalt B Boyce A Endotext. MDText.com, South Dartmouth, MA2000Google Scholar Although the aetiology of long COVID remains speculative, clear evidence that a state of chronic inflammation can persist even in asymptomatic survivors is accruing.6Phetsouphanh C Darley DR Wilson DB et al.Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection.Nat Immunol. 2022; 23: 210-216Crossref PubMed Scopus (122) Google Scholar, 7Frere JJ Serafini RA Pryce KD et al.SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery.Sci Transl Med. 2022; 14: eabq3059Crossref PubMed Scopus (15) Google Scholar During such inflammation, the composition and functional capacity of HDL also changes and it has thus been called pro-inflammatory or pro-atherogenic HDL. Serum amyloid A, released during inflammation, interferes with the ability of HDL to protect LDL from pro-atherogenic modifications such as oxidation and glycation. Furthermore, decreases in apolipoprotein A1 in HDL reduce its capacity to receive excess tissue cholesterol, which is believed to occur through the ATP binding cassette A1 and to be an important early phase of reverse cholesterol transport.5Feingold KR Grunfeld C The Effect of inflammation and infection on lipids and lipoproteins.in: Feingold KR Anawalt B Boyce A Endotext. MDText.com, South Dartmouth, MA2000Google Scholar The effects of chronic inflammation on lipoprotein metabolism have been extensively investigated in obesity. Adipose tissue, particularly when it is centrally located (metabolic syndrome), contains inflammatory cells that release cytokines causing dyslipidaemia. Reversal by bariatric surgery restores triglyceride and HDL metabolism towards normality, but has little effect on LDL cholesterol.8Adam S Ho JH Liu Y et al.Bariatric surgery-induced high-density lipoprotein functionality enhancement is associated with reduced inflammation.J Clin Endocrinol Metab. 2022; 107: 2182-2194Crossref PubMed Scopus (0) Google Scholar Persisting effects on LDL after the apparent resolution of inflammation are unexplained and remind us just how imperfect our knowledge is of what determines LDL cholesterol concentrations in adulthood. Recently, because of their potential to lower LDL cholesterol by pharmacological inhibition, interest has sparked in two factors that influence the balance between LDL catabolism and production. These are proprotein convertase subtilisin or kexin type 9 (PCSK9), which has a major effect on hepatic receptor-mediated LDL catabolism9Seidah NG Prat A The multifaceted biology of PCSK9.Endocr Rev. 2022; 43: 558-582Crossref PubMed Scopus (20) Google Scholar and angiopoietin-like protein 3 (ANGPTL3), which regulates the production of LDL from its precursor very low density lipoprotein.10Adam RC Mintah IJ Alexa-Braun CA et al.Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance.J Lipid Res. 2020; 61: 1271-1286Summary Full Text Full Text PDF PubMed Scopus (68) Google Scholar It has been hypothesised that both can increase during inflammation.9Seidah NG Prat A The multifaceted biology of PCSK9.Endocr Rev. 2022; 43: 558-582Crossref PubMed Scopus (20) Google Scholar, 10Adam RC Mintah IJ Alexa-Braun CA et al.Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance.J Lipid Res. 2020; 61: 1271-1286Summary Full Text Full Text PDF PubMed Scopus (68) Google Scholar, 11Abu-Farha M Ghosh A Al-Khairi I Madiraju SRM Abubaker J Prentki M The multi-faces of Angptl8 in health and disease: novel functions beyond lipoprotein lipase modulation.Prog Lipid Res. 2020; 80: 101067Crossref PubMed Scopus (23) Google Scholar We clearly need to learn more about how cholesterol metabolism is permanently imprinted by nutrition and infection or inflammation. I declare no competing interests. Risks and burdens of incident dyslipidaemia in long COVID: a cohort studyOur findings suggest increased risks and 1-year burdens of incident dyslipidaemia and incident lipid-lowering medications use in the post-acute phase of COVID-19 infection. Post-acute care for those with COVID-19 should involve attention to dyslipidaemia as a potential post-acute sequela of SARS-CoV-2 infection. Full-Text PDF