Metabolite profile of COVID-19 revealed by UPLC-MS/MS-based widely targeted metabolomics

Abstract

The metabolic characteristics of COVID-19 disease are still largely unknown. Here, 44 patients with COVID-19 (31 mild COVID-19 patients and 13 severe COVID-19 patients), 42 healthy controls (HC), and 42 patients with community-acquired pneumonia (CAP), were involved in the study to assess their serum metabolomic profiles. We used widely targeted metabolomics based on an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The differentially expressed metabolites in the plasma of mild and severe COVID-19 patients, CAP patients, and HC subjects were screened, and the main metabolic pathways involved were analyzed. Multiple mature machine learning algorithms confirmed that the metabolites performed excellently in discriminating COVID-19 groups from CAP and HC subjects, with an area under the curve (AUC) of 1. The specific dysregulation of AMP, dGMP, sn-glycero-3-phosphocholine, and carnitine was observed in the severe COVID-19 group. Moreover, random forest analysis suggested that these metabolites could discriminate between severe COVID-19 patients and mild COVID-19 patients, with an AUC of 0.921. This study may broaden our understanding of pathophysiological mechanisms of COVID-19 and may offer an experimental basis for developing novel treatment strategies against it.

Label-Free SERS for Rapid Differentiation of SARS-CoV-2-Induced Serum Metabolic Profiles in Non-Hospitalized Adults

“…Major metabolites (hypoxanthine, uric acid, and lipids) assigned to the differential spectral markers are associated with SARS-CoV-2 infection, , and have been utilized to discriminate between mild COV+ and healthy adults. , Some authors have also explored the evolution of metabolic features at different time intervals post-symptom onset as correlates of COVID-19 pathogenesis and immune response . Recently, machine learning-aided metabolomics revealed COVID-19-specific trends of dysregulation, similar to those reported in the present work, in various classes of biological compounds, including lipids (1450 cm –1 ), proteins (1250 cm –1 ), amino acids (630, 1093 cm –1 ), and adenine and its derivatives, such as methyladenosine, in mildly infected patients. , The levels of metabolic components decreased in the longitudinal plasma of the COV+ after ∼3 weeks post-symptom onset, before rising gradually, reaching a similar metabolic state to that detected for the COV– subjects 14 weeks post-infection, which is in agreement with the probable metabolic healing process of COV+ patients observed in our results presented in Figure a.…”

“…Major metabolites (hypoxanthine, uric acid, and lipids) assigned to the differential spectral markers are associated with SARS-CoV-2 infection, 39 , 40 and have been utilized to discriminate between mild COV+ and healthy adults. 8 , 41 Some authors have also explored the evolution of metabolic features at different time intervals post-symptom onset as correlates of COVID-19 pathogenesis and immune response.…”

Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19

“…Specifically, IL-18, IL-6, IFN-γ, IP-10 and RANTES exhibited strong positive correlations with the pro-atherogenic LDL sub-particles and negative correlation with HDL particles and sub-particles ( Lodge et al, 2021a ), while M-CSF and IL-12p40 correlate with plasma levels of glycylproline and long-chain acylcarnitines in COVID-19 patients ( Yang et al, 2022 ). That said, the COVID-19 interplay with the inflammatory system is not unique ( Liu et al, 2022 ) and more than 20 metabolites were associated equally strongly to other unrelated severe pneumonia events ( Julkunen et al, 2021 ). In line with this observation, the vast majority of tuberculosis (TB) patients experienced a severe SARS-CoV-2 post-TB infection ( Diboun et al, 2022 ).…”

Crosstalk between COVID-19 Infection and Kidney Diseases: A Review on the Metabolomic Approaches

“…The lack of anti-inflammatory signals brought on by the reduction of 15-HETE may be a factor in the increased inflammation observed during COVID-19 infection [ 172 ]. A targeted metabolomic study analyzed and identified AMP, dGMP, sn-glycerol-3-phosphocholine, and carnitine metabolites that were dysregulated in patients with COVID-19 [ 173 ]. The study by Lee et al analyzing plasma metabolite and protein levels, as well as single-cell multi-omics analyses collected during the first week after clinical diagnosis, metabolic changes associated with peripheral immune responses in 198 COVID-19 patients were reported in a large cohort study of healthy donors.…”