High plasma concentration of non-esterified polyunsaturated fatty acids is a specific feature of severe COVID-19 pneumonia

Abstract

COVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological (including plasma cytokines) features were assessed. Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response but higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels. NEFAs and PUFAs concentrations were negatively correlated with the number of ventilator-free days. Among hospitalized patients with severe pneumonia, COVID-19 is independently associated with higher NEFAs (mainly linoleic and arachidonic acids) and lower apolipoprotein E and HDL concentrations. These features might act as mediators in COVID-19 pathogenesis and emerge as new therapeutic targets. Further investigations are required to define the role of NEFAs in the pathogenesis and the dysregulated immune response associated with COVID-19.Trial registration: NCT04435223.

Machine learning and semi-targeted lipidomics identify distinct serum lipid signatures in hospitalized COVID-19-positive and COVID-19-negative patients

“…Our study found a significant, and very relevant, increase in serum long-chain TG concentrations in COVID-19-positive compared with COVID-19-negative patients. TG are carried in the circulation packed in the very-low density lipoproteins (VLDL), and studies agree in that the levels of triglycerides, VLDL, and polyunsaturated fatty acids are increased in COVID-19 and Ebola virus disease [23] , [58] , [59] , [60] . Therefore, this elevation in long-chain TG concentrations could be related to the immune response, although the mechanisms behind its deregulation are not well elucidated.…”

Syrian hamsters as a model of lung injury with SARS-CoV-2 infection: Pathologic, physiologic, and detailed molecular profiling

“…There are several reports documenting lipid profiles of plasma in COVID-19 patients emphasizing marked changes in phospholipids, neutral lipids (particularly, triacylglycerols, cholesterol esters) and non-esterified fatty acids related to the severity and transition from the pro-inflammatory to the resolution phases of the disease, as well as in cured patients [77] , [78] , [79] , [80] . In few cases, lipidomics studies were conducted in COVID-19 BAL samples, thus reflecting lipidomics changes in the lungs of intubated patients.…”

Coronavirus Infection and Cholesterol Metabolism

“…When compared with healthy individuals, patients with dyslipidemia-related diseases are more likely to be infected by SARS-CoV-2 ( 234 , 235 ). Also, SARS-CoV-2 infection caused some COVID-19 patients to have lower serum cholesterol levels (e.g., 27HC, total cholesterol, high density lipoprotein cholesterol, and low-density lipoprotein cholesterol), while triglyceride and non-esterified polyunsaturated fatty acid levels were up-regulated ( Figures 2B-b ) ( 27 , 236 – 238 ). In particular, decreased serum HDL-C levels are positively correlated with COVID-19 infection severity ( 239 ).…”