Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19
MD Álvaro Aparisi, MD Carolina Iglesias-Echeverría, MD Cristina Ybarra-Falcón, MD, PhD Iván Cusácovich, MD Aitor Uribarri, MD Mario García-Gómez, MD Raquel Ladrón, Raúl Fuertes, MD Jordi Candela, MD Williams Hinojosa, MD Carlos Dueñas, MD, PhD Roberto González, MD Leonor Nogales, MD Dolores Calvo, MSc Manuel Carrasco-Moraleja, J Alberto San Román, MD, PhD Ignacio J Amat-Santos, MD, PhD David Andaluz-Ojeda
doi:10.1101/2020.10.06.20207092
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 .
Methods: We performed a retrospective single-center study of consecutively admitted patients between March 1 st and May 15 th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. Results: A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease with complete resolution among survivors. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein > 88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia < 1,000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission.
Conclusion: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immuneinflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.
References
Alsaadi, Jones, Membrane binding proteins of coronaviruses, Future Virol
Cirstea, Walley, Russell, Brunham, Genga et al., Decreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis, J Crit Care
Dupic, Huet, Duranteau, Coenzyme Q10 deficiency in septic shock patients, Crit Care
Esteve, Ricart, Fernández-Real, Dyslipidemia and inflammation: an evolutionary conserved mechanism, Clin Nutr
Fan, Wang, Ye, Low-density lipoprotein is a potential predictor of poor prognosis in patients with coronavirus disease, Metabolis
Feng, Wei, Chaugai, Association Between Low-Density Lipoprotein Cholesterol Levels and Risk for Sepsis Among Patients Admitted to the Hospital With Infection, Jama Netw Open
Funderburg, Mehta, Lipid Abnormalities and Inflammation in HIV Inflection, Curr Hivaids Rep
Guirgis, Donnelly, Dodani, Cholesterol levels and long-term rates of communityacquired sepsis, Crit Care
Hu, Chen, Wu, He, Ye, Declined serum high density lipoprotein cholesterol is associated with the severity of COVID-19 infection, Clin Chim Acta
Hu, Chen, Wu, He, Ye, Low Serum Cholesterol Level Among Patients with COVID-19 Infection in Wenzhou
Kaysen, Ye, Raimann, Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results, J Lipid Res
Madjid, Safavi-Naeini, Solomon, Vardeny, Potential Effects of Coronaviruses on the Cardiovascular System, Jama Cardiol
Madsen, Varbo, Tybjaerg-Hansen, Frikke-Schmidt, Nordestgaard, U-shaped relationship of HDL and risk of infectious disease: two prospective population-based cohort studies, Eur Heart J
Maile, Sigakis, Stringer, Jewell, Engoren, Impact of the pre-illness lipid profile on sepsis mortality, J Crit Care
Meher, Bhattacharjya, Chakraborty, Membrane Cholesterol Modulates Oligomeric Status and Peptide-Membrane Interaction of Severe Acute Respiratory Syndrome Coronavirus Fusion Peptide, J Phys Chem B
Merad, Martin, Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages, Nat Rev Immunol
Na Ldl-C, None
Na, Tc, NA HDL High-density lipoprotein cholesterol: LDL-c: Low-density lipoprotein cholesterol; NA: Not applicable; TC: Total cholesterol: TG Triglycerides * Only in survivors, HDL
Pacanowski, Frye, Enogieru, Plasma Coenzyme Q10 Predicts Lipid-lowering Response to High-Dose Atorvastatin, J Clin Lipidol
Pons, Fodil, Azoulay, Zafrani, The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection, Crit Care
Radenkovic, Chawla, Pirro, Sahebkar, Banach, Cholesterol in Relation to COVID-19: Should We Care about It?, J Clin Medicine
Robertson, Peters, Mcinnes, Sattar, Changes in lipid levels with inflammation and therapy in RA: a maturing paradigm, Nat Rev Rheumatol
Rosenson, Brewer, Ansell, Dysfunctional HDL and atherosclerotic cardiovascular disease, Nat Rev Cardiol
Singer, Deutschman, Seymour, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), Jama
Tall, Yvan-Charvet, Cholesterol, inflammation and innate immunity, Nat Rev Immunol
Tanaka, Couret, High-density lipoproteins during sepsis: from bench to bedside, Crit Care
Tanaka, Diallo, Delbosc, High-density lipoprotein (HDL) particle size and concentration changes in septic shock patients, Ann Intensive Care
Tien, Hepatitis C Virus-Associated Alterations in Lipid and Lipoprotein Levels: Helpful or Harmful to the Heart?, Clin Infect Dis
Walley, Boyd, Kong, Russell, Low Low-Density Lipoprotein Levels Are Associated With, But Do Not Causally Contribute to, Increased Mortality in Sepsis*, Crit Care Med
Wei, Wan, Zhang, Cholesterol Metabolism--Impact for SARS-CoV-2 Infection Prognosis, Entry, and Antiviral Therapies
Wei, Zeng, Su, Hypolipidemia is associated with the severity of COVID-19, J Clin Lipidol
Who, Coronavirus disease
Wu, Zhou, Sun, Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection, Sci Rep-uk
Yan, Chu, Yang, Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication, Viruses
