Metabolomic/lipidomic profiling of COVID-19 and individual response to tocilizumab

Abstract

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.

Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection

“…A pivotal metabolic shift in COVID-19 patients is represented by a disproportionate reduction in nutrient circulation [ 47 ]. In particular, there is a preferential depletion of metabolites associated with the TCA cycle with increasing disease severity [ 47 , 54 ], which has been confirmed by multiple independent studies [ 45 , 55 , 56 ]. It should be noted that the levels of a number of plasma fatty acid metabolites from recovered COVID-19 patients with impaired lung function were not normalized, indicating a lack of complete recovery [ 54 , 57 ].…”

Molecular Phenomic Approaches to Deconvolving the Systemic Effects of SARS-CoV-2 Infection and Post-acute COVID-19 Syndrome

“…Harmonisation of technology and approach in phenomic analytical chemistry has been a longterm objective in the metabolic phenotyping field (Lindon et al 2005). In the case of COVID-19 metabolic studies, standardization, and cross-validation of sample preparation methods has been investigated and recommendations made to ensure robust metabolic data collection that enable interlaboratory comparisons (Loo et al 2020;Meoni et al 2021). In the case of NMR spectroscopy, protocol harmonization already exists for in vitro diagnostic applications such as plasma metabolites and lipoproteins (Meoni et al 2021) and this has led to highly complementary analytical data being generated in multiple laboratories studying COVID-19 round the world (Jimenez et al 2018;Barberis et al 2020) which gives confidence that these biomarker signatures of the disease are accurate and translatable across populations.…”

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

“…We and others have observed metabolic heterogeneity in the biomarker responses in acute COVID-19 patients showing multiple systemic effects. 23 − 28 We postulate that full functional recovery from the disease, by most of the patients without pre-existing comorbidities, is likely to be reflected in a normalization of the disrupted sentinel biomarker parameters and the overall metabolic phenotype. The process of multilevel recovery can be considered to be functionally equivalent to the reverse of disease onset and progression “phenoconversion”, 23 , 24 during which the measured metabolic profile shifts from normality to one typical of the disease or its subphenotypes.…”