Metabolic and Lipidomic Markers Differentiate COVID-19 From Non-Hospitalized and Other Intensive Care Patients

Abstract

Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus, there is increasing interest in metabolic and lipoprotein signatures of the disease, and early analyses have demonstrated a metabolic pattern typical for atherosclerotic and hepatic damage in COVID-19 patients. However, it remains unclear whether this is specific for COVID-19 and whether the observed signature is caused by the disease or rather represents an underlying risk factor. To answer this question, we have analyzed 482 serum samples using nuclear magnetic resonance metabolomics, including longitudinally collected samples from 12 COVID-19 and 20 cardiogenic shock intensive care patients, samples from 18 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody-positive individuals, and single time point samples from 58 healthy controls. COVID-19 patients showed a distinct metabolic serum profile, including changes typical for severe dyslipidemia and a deeply altered metabolic status compared with healthy controls. Specifically, very-low-density lipoprotein and intermediate-density lipoprotein particles and associated apolipoprotein B and intermediate-density lipoprotein cholesterol were significantly increased, whereas cholesterol and apolipoprotein A2 were decreased. Moreover, a similarly perturbed profile was apparent when compared with other patients with cardiogenic shock who are in the intensive care unit when looking at a 1-week time course, highlighting close links between COVID-19 and lipid metabolism. The metabolic profile of COVID-19 patients distinguishes those from healthy controls and also from patients with cardiogenic shock. In contrast, anti-SARS-CoV-2 antibody-positive individuals without acute COVID-19 did not show a significantly perturbed metabolic profile compared with age- and sex-matched healthy controls, but SARS-CoV-2 antibody-titers correlated significantly with metabolic parameters, including levels of glycine, ApoA2, and small-sized low- and high-density lipoprotein subfractions. Our data suggest that COVID-19 is associated with dyslipidemia, which is not observed in anti-SARS-CoV-2 antibody-positive individuals who have not developed severe courses of the disease. This suggests that lipoprotein profiles may represent a confounding risk factor for COVID-19 with potential for patient stratification.

Profiling metabolites and lipoproteins in COMETA, an Italian cohort of COVID-19 patients

“…Several metabolomic studies have indicated that COVID-19 is associated with abnormalities in the concentration of metabolites and lipoproteins in plasma or serum [ 6 – 20 ]. These findings suggest the reprogramming of some metabolic pathways alongside the reprogramming of the immune system.…”

Coronavirus disease 2019 (COVID‐19) update: From metabolic reprogramming to immunometabolism

“…[139][140][141] Vascular impairment and thromboembolisms add to the disease's reported multisystem destruction and increased mortality. 142 Schmelter et al 141…”

“…Furthermore, COVID‐19 individuals have neurological symptoms and renal and hepatic impairment 139‐141 . Vascular impairment and thromboembolisms add to the disease's reported multisystem destruction and increased mortality 142 . Schmelter et al 141 used an experiment to evaluate the metabolic and lipoprotein profiling of hospitalized COVID‐19 cases to many healthy controls and a group of cardiogenic shock cases receiving in the same intensive care unit (ICU) who tested negative for COVID‐19.…”

Role of Diet and Nutrients in SARS-CoV-2 Infection: Incidence on Oxidative Stress, Inflammatory Status and Viral Production

“…Examination of COVID-19 at the beginning of sickness and through to the progress of the infection differs from asymptomatic to acute pneumonia with severe respiratory distress syndrome, with the most usual symptoms being cough, shortness of breath, diarrhea, fever and tiredness [ 3 , 4 ]. Moreover, contaminated individuals by this RNA virus presented venous thromboembolic incidents linked to endothelial damage and hypercoagulability, immoderate inflammatory status with cytokine storm, immune dysregulation, cholesterol metabolism abnormalities, oxidative stress, hypertension and new onset diabetes [ 5 , 6 , 7 , 8 ].…”