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Authors:BruzzoneBizkarguenaga et al. 

Journal/ Pre-Print:SSRN, In Review for Cell Reports 

Tags: Metabolomics, Lipidomics, Systemic Metabolism 

Research Highlights 

  1. SARS-CoV-2 is associated with altered systemic lipid metabolism and increased circulation of triacylglyceride-laden LDL particles. 

  1. Increase in circulating ketobodies (3-hydroxybutyric acid, acetoacetic acid) indicates altered hepatic lipid metabolism. 

  1. Amino acid dysbalance with increases in phenylalanine and hydroxybutiryc acid may be indicative of hepatic oxidative stress. 

Summary 

Viral infections impact on the host cellular and systemic lipid metabolism. Using NMR spectroscopy, the authors measured the lipidomic and metabolomic profile of 263 symptomatic COVID19 patients and 280 control serum samples collected before the outbreak of SARS-CoV-2. The study finds that serum from SARS-CoV-2 patients contains a shift in circulating lipoprotein profiles with enrichment of various triacylglyceride-rich lipoprotein and an increase in ApoB-to-ApoA1 (as proxy for LDL-to-HDL) ratio indicating an increased risk for cardiovascular disease. Further, the study demonstrates an increase in circulating ketone bodies which indicates of altered liver metabolism, which is coherent with increase of 2- hydroxybutiryc acid, a marker for hepatic oxidative stress. In brief, this summary is in line with previous reports showing dyslipidemia in during SARS-CoV-2 and may provide some insights in the potential causes for cardiovascular events observed post-COVID19 infections.   

Impact for SARS-CoV2/COVID19 research efforts  

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19 

This study confirms previous findings showing dyslipidemia during SARS-CoV-2 infection. It will allow subsequent studies to identify the consequences (e.g. association to increased risk of cardiovascular events) and reason for these alterations (e.g. increased energy expenditure during viral infection). 

Study Type  

  • Clinical Cohort study (descriptive serology study) 

Strengths and limitations of the paper 

Novelty: This study is unique in terms of cohort size (with more than 250  

individuals per group) allowing in depth analysis of metabolic and lipidomic changes. Further, it is the first NMR based analysis of lipids and other metabolites. It interestingly provides evidence to hepatic dysfunction/stress and a systemic increase in ketobodies 

Standing in the field:The study confirms similar findings previously observed by Shen et al.  

(Cell, 2020) which also observed a reduced level of ApoA1 in with increasing COVID19 severity. It further confirms previous reports of increased triglycerides in SARS-CoV-2 (Wu et al., National Science Review, 2020). 

Appropriate statistics:Statistics looks legit. 

Viral model used:Serum samples of SARS-CoV-2 patients. 

Translatability:Low. 

Main limitations: It seems that most of the analysis has been down comparing the two cohorts of serum (SARS-CoV-2 vs. control), although there is a clear age difference between the groups. The authors do show that the groups still separate when normalized for age. However subsequent analysis would have benefited to be done in the age-matched situation as age is known to promote dyslipidemia 

It would have been beneficial to provide more patient information with regards to co-morbidities of the different cohortsespecially obesity. 

The authors also have some individuals who recovered from SARS-CoV-2 and showed signs of seroconversion. It would have been beneficial to know whether recovered patients normalise their lipid and metabolic profile or sustain dyslipidemic conditions.