Distinct Metabolic Profile Associated with a Fatal Outcome in COVID-19 Patients during the Early Epidemic in Italy

Saccon, Elisa; Bandera, Alessandra; Sciumè, Mariarita; Mikaeloff, Flora; Lashari, Abid Ali; Aliberti, Stefano; Sachs, Michael; Billi, Filippo; Blasi, Francesco; Gabriel, Erin E.; Costantino, Giorgio; Roberto, Pasquale De; Krishnan, Shuba; Gori, Andrea; Peyvandi, Flora; Scudeller, Luigia; Canetta, Ciro; Lorson, Christian L.; Valenti, Luca; Singh, Kamal; Baldini, Luca; Fracchiolla, Nicola Stefano; Neogi, Ujjwal

doi:10.1128/spectrum.00549-21

Cited by 7 publications

(6 citation statements)

References 19 publications

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“…Metabolic comorbidities including obesity, diabetes, cardiovascular, and hypertension have been associated with poor prognosis in COVID-19 ( 75 ). A certain degree of metabolic dysregulation has been found in COVID-19, possibly due to immune-triggered inflammation and hypercoagulability, as well as microbial changes in host physiology ( 10 , 76 ). Indeed, COVID-19 patients with lower levels of high-density lipoprotein (HDL) cholesterol are more susceptible to hospitalization, while low-density lipoprotein (LDL) cholesterol was associated with higher inflammation ( 77 ).…”

Section: Diagnostic and Prognostic Value Of Biomarkersmentioning

confidence: 99%

“…Longer duration of invasive mechanical ventilation was associated with the kynurenine and p -cresol sulfate pathways ( 8 ). Several markers of metabolic function identified via metabolomic analysis were associated with in-hospital mortality, including cyclic adenosine monophosphate (cAMP), which plays a role in SARS-CoV2 endocytosis in the initial phase of the disease ( 10 ). Another major signature of the serum metabolome in COVID-19 was lactic acid, as well as spermidine and spermine.…”

Section: Future Perspectives: Metabolomic and Proteomic Biomarkers An...mentioning

confidence: 99%

“…Several biomarkers other than cytokines have been found altered in COVID-19, and are associated with diagnosis, prognosis and outcomes ( 7 ). Some of these biomarkers can be easily used to predict disease severity, hospitalization, intensive care unit (ICU) admission, and mortality, while others, like metabolomic and proteomic analysis, are still of purely investigational concern and difficult to translate into clinical practice, despite their prognostic potential ( 8 – 10 ).…”

Section: Introductionmentioning

confidence: 99%

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Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19

et al. 2022

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Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes a wide spectrum of clinical manifestations, with progression to multiorgan failure in the most severe cases. Several biomarkers can be altered in coronavirus disease 2019 (COVID-19), and they can be associated with diagnosis, prognosis, and outcomes. The most used biomarkers in COVID-19 include several proinflammatory cytokines, neuron-specific enolase (NSE), lactate dehydrogenase (LDH), aspartate transaminase (AST), neutrophil count, neutrophils-to-lymphocytes ratio, troponins, creatine kinase (MB), myoglobin, D-dimer, brain natriuretic peptide (BNP), and its N-terminal pro-hormone (NT-proBNP). Some of these biomarkers can be readily used to predict disease severity, hospitalization, intensive care unit (ICU) admission, and mortality, while others, such as metabolomic and proteomic analysis, have not yet translated to clinical practice. This narrative review aims to identify laboratory biomarkers that have shown significant diagnostic and prognostic value for risk stratification in COVID-19 and discuss the possible clinical application of novel analytic strategies, like metabolomics and proteomics. Future research should focus on identifying a limited but essential number of laboratory biomarkers to easily predict prognosis and outcome in severe COVID-19.

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Section: Diagnostic and Prognostic Value Of Biomarkersmentioning

confidence: 99%

Section: Future Perspectives: Metabolomic and Proteomic Biomarkers An...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19

et al. 2022

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“…This metabolic signature seems to be rather homogeneous worldwide, with equivalent results obtained when considering very distant geographical and cultural regions such as Mexico ( López-Hernández et al, 2021 ), Italy ( Saccon et al, 2021 ; Ghini et al, 2022b ; Ciccarelli et al, 2022 ), and Africa ( Li X. et al, 2022 ). Instead, characteristic but distinct metabotypes can be associated to pregnant women ( Id et al, 2022 ), newborn ( Kontou et al, 2021 ) and infantile ( Wang et al, 2021 ) COVID-19 population.…”

Section: Metabolic Signature Of the Acute Phase Of Sars-cov-2 Infectionmentioning

confidence: 54%

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

Bruzzone

Conde

Embade

et al. 2023

Front. Mol. Biosci.

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COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.

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“…The period of sample collection was during a particularly challenging time in Milan, since it was the first major European city to experience the COVID-19 pandemic. Consequently, patient samples for highly selected research purposes were scarce 63 , 64 . The low sample volume available meant we had to adjust the routine replicate experimental practices into singlicate analysis and use a minimal volume of 70 μl of plasma for NMR.…”

Section: Discussionmentioning

confidence: 99%

Reduced circulating FABP2 in patients with moderate to severe COVID-19 may indicate enterocyte functional change rather than cell death

Assante

Tourna

Carpani

et al. 2022

Sci Rep

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The gut is of importance in the pathology of COVID-19 both as a route of infection, and gut dysfunction influencing the severity of disease. Systemic changes caused by SARS-CoV-2 gut infection include alterations in circulating levels of metabolites, nutrients and microbial products which alter immune and inflammatory responses. Circulating plasma markers for gut inflammation and damage such as zonulin, lipopolysaccharide and β-glycan increase in plasma along with severity of disease. However, Intestinal Fatty Acid Binding Protein / Fatty Acid Binding Protein 2 (I-FABP/FABP2), a widely used biomarker for gut cell death, has paradoxically been shown to be reduced in moderate to severe COVID-19. We also found this pattern in a pilot cohort of mild (n = 18) and moderately severe (n = 19) COVID-19 patients in Milan from March to June 2020. These patients were part of the first phase of COVID-19 in Europe and were therefore all unvaccinated. After exclusion of outliers, patients with more severe vs milder disease showed reduced FABP2 levels (median [IQR]) (124 [368] vs. 274 [558] pg/mL, P < 0.01). A reduction in NMR measured plasma relative lipid-CH3 levels approached significance (median [IQR]) (0.081 [0.011] vs. 0.073 [0.024], P = 0.06). Changes in circulating lipid levels are another feature commonly observed in severe COVID-19 and a weak positive correlation was observed in the more severe group between reduced FABP2 and reduced relative lipid-CH3 and lipid-CH2 levels. FABP2 is a key regulator of enterocyte lipid import, a process which is inhibited by gut SARS-CoV-2 infection. We propose that the reduced circulating FABP2 in moderate to severe COVID-19 is a marker of infected enterocyte functional change rather than gut damage, which could also contribute to the development of hypolipidemia in patients with more severe disease.

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Distinct Metabolic Profile Associated with a Fatal Outcome in COVID-19 Patients during the Early Epidemic in Italy

Cited by 7 publications

References 19 publications

Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19

Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19

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

Reduced circulating FABP2 in patients with moderate to severe COVID-19 may indicate enterocyte functional change rather than cell death

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