An Altered Metabolism in Leukocytes Showing in vitro igG Memory From SARS-CoV-2-Infected Patients

Fanelli, Guido; Gevi, Federica; Zarletti, Gianpaolo; Tiberi, Massimo; Molfetta, Veronica De; Scapigliati, Giuseppe; Timperio, Anna Maria

doi:10.3389/fmolb.2022.894207

Cited by 3 publications

(6 citation statements)

References 28 publications

(31 reference statements)

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“…Mass spectrometry measurements indicated that some altered metabolisms, such as the methionine cycle, arginine cycle, and tryptophan cycle, were impacted by COVID-19-induced changes in leukocytes. This review supports the idea that the metabolic profile changes observed in unstimulated PBMCs until after 90 days of SARS-CoV2 infection [ 20 , 22 ] could serve as a tool for evaluating disease, the modulation metabolism involved in innate and adaptive immunity, thus providing a new method for monitoring the risk of SARS-CoV2 reinfection. The analysis of these metabolites might represent a biomarker of the effective and long-standing antiviral activation of PBMCs.…”

Section: Discussionsupporting

confidence: 73%

“…In this regard, accurate tests that can identify the SARS-CoV2 virus and monitor antiviral antibodies are essential for identifying those who have had an immune response to the virus, aiding in virus management and surveillance and combating the COVID-19 pandemic [ 19 ]. Furthermore, understanding the molecular mechanism involved in physiological recovery from viral infections and immune activities in leukocytes [ 20 ] became crucial for knowing the antibody-mediated immune response to SARS-CoV2.…”

Section: Metabolic Rewiring In Sars-cov2-infected Patientsmentioning

confidence: 99%

“…In the report of Fanelli et al [ 20 ], we provide a description of metabolites that describe the later phases of immune defense against SARS-CoV2 infection, which involve the absence of circulating antibodies but the presence of antibody memory. We examined the metabolic profiles of 41 cell cultures of peripheral blood mononuclear cells (PBMCs) and discovered that 17 of them had in vitro IgG memory for spike S1 antigen 60–90 days post infection, as previously indicated by in-cell ELISA [ 19 ].…”

Section: Metabolic Rewiring In Sars-cov2-infected Patientsmentioning

confidence: 99%

“…In fact, most of the disturbed AAs recovered in convalescing subjects after 1 month post SARS-CoV2 infection [ 52 ]. Amino acid metabolic pathways central to leukocytes with in vitro IgG memory from SARS-CoV2-infected patients focused primarily on three major cycles (methionine cycle, arginine cycle, tryptophan cycle) involved in physiological recovery from viral infection [ 20 , 22 ]. The metabolomic fingerprint of unstimulated PBMCs analyzed up to 90 days after SARS-CoV2 infection is characterized by the dysregulation of some amino acids, especially methionine, tryptophan, and arginine metabolism ( Figure 1 ).…”

Section: Amino Acid Metabolismmentioning

confidence: 99%

“…The green box shows the methionine and arginine metabolism pathways that were upregulated after infection, whereas the red box shows the tryptophan pathway that was downregulated in IgGm+ samples. Taken together, these pathways were involved in physiological recovery from viral infection and immune activity [ 20 , 22 ]. S-adenosylmethionine (AdoMet); S-adenosyl-L-homocysteine (AdoHcy); indoleamine 2,3-dioxygenase 1 (IDO1); aryl hydrocarbon receptor (AhR).…”

Section: Figurementioning

confidence: 99%

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Amino Acid Metabolism in Leukocytes Showing In Vitro IgG Memory from SARS-CoV2-Infected Patients

Fanelli,

Lelli,

Rinalducci

et al. 2024

Diseases

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The immune response to infectious diseases is directly influenced by metabolic activities. COVID-19 is a disease that affects the entire body and can significantly impact cellular metabolism. Recent studies have focused their analysis on the potential connections between post-infection stages of SARS-CoV2 and different metabolic pathways. The spike S1 antigen was found to have in vitro IgG antibody memory for PBMCs when obtaining PBMC cultures 60–90 days post infection, and a significant increase in S-adenosyl homocysteine, sarcosine, and arginine was detected by mass spectrometric analysis. The involvement of these metabolites in physiological recovery from viral infections and immune activity is well documented, and they may provide a new and simple method to better comprehend the impact of SARS-CoV2 on leukocytes. Moreover, there was a significant change in the metabolism of the tryptophan and urea cycle pathways in leukocytes with IgG memory. With these data, together with results from the literature, it seems that leukocyte metabolism is reprogrammed after viral pathogenesis by activating certain amino acid pathways, which may be related to protective immunity against SARS-CoV2.

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Section: Discussionsupporting

confidence: 73%

Section: Metabolic Rewiring In Sars-cov2-infected Patientsmentioning

confidence: 99%

Section: Metabolic Rewiring In Sars-cov2-infected Patientsmentioning

confidence: 99%

Section: Amino Acid Metabolismmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Amino Acid Metabolism in Leukocytes Showing In Vitro IgG Memory from SARS-CoV2-Infected Patients

Fanelli,

Lelli,

Rinalducci

et al. 2024

Diseases

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Amino acids, post-translational modifications, nitric oxide, and oxidative stress in serum and urine of long COVID and ex COVID human subjects

et al. 2023

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In this study, we investigated the status of amino acids, their post-translational modifications (PTM), major nitric oxide (NO) metabolites and of malondialdehyde (MDA) as a biomarker of oxidative stress in serum and urine samples of long COVID (LoCo, n = 124) and ex COVID (ExCo, n = 24) human subjects collected in 2022. Amino acids and metabolites were measured by gas chromatography–mass spectrometry (GC–MS) methods using stable-isotope labelled analogs as internal standards. There were no differences with respect to circulating and excretory arginine and asymmetric dimethylarginine (ADMA). LoCo participants excreted higher amounts of guanidino acetate than ExCo participants (17.8 ± 10.4 µM/mM vs. 12.6 ± 8.86 µM/mM, P = 0.005). By contrast, LoCo participants excreted lower amounts of the advanced glycation end-product (AGE) NG-carboxyethylarginine (CEA) than ExCo participants did (0.675 ± 0.781 µM/mM vs. 1.16 ± 2.04 µM/mM, P = 0.0326). The serum concentrations of MDA did not differ between the groups, indicating no elevated oxidative stress in LoCo or ExCo. The serum concentration of nitrite was lower in LoCo compared to ExCo (1.96 ± 0.92 µM vs. 2.56 ± 1.08 µM; AUC, 0.718), suggesting altered NO synthesis in the endothelium. The serum concentration of nitrite correlated inversely with the symptom anxiety (r = − 0.293, P = 0.0003). The creatinine-corrected urinary excretion of Lys and its metabolite L-5-hydroxy-Lys correlated positively with COVID toes (r = 0.306, P = 0.00027) and sore throat (r = 0.302, P = 0.0003). Our results suggest that amino acid metabolism, PTM and oxidative stress are not severely affected in long COVID. LoCo participants may have a lower circulating NO reservoir than ExCo.

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An untargeted metabolomic approach to investigate antiviral defence mechanisms in memory leukocytes secreting anti-SARS-CoV-2 IgG in vitro

Gevi

Fanelli

Lelli

et al. 2023

Sci Rep

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Evidence shows that individuals infected by SARS-CoV-2 experience an altered metabolic state in multiple organs. Metabolic activities are directly involved in modulating immune responses against infectious diseases, yet our understanding of how host metabolism relates to inflammatory responses remains limited. To better elucidate the underlying biochemistry of the leukocyte response, we focused our analysis on possible relationships between SARS-CoV-2 post-infection stages and distinct metabolic pathways. Indeed, we observed a significant altered metabolism of tryptophan and urea cycle pathways in cultures of peripheral blood mononuclear cells obtained 60–90 days after infection and showing in vitro IgG antibody memory for spike-S1 antigen (n = 17). This work, for the first time, identifies metabolic routes in cell metabolism possibly related to later stages of immune defence against SARS-CoV-2 infection, namely, when circulating antibodies may be absent but an antibody memory is present. The results suggest reprogramming of leukocyte metabolism after viral pathogenesis through activation of specific amino acid pathways possibly related to protective immunity against SARS-CoV-2.

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An Altered Metabolism in Leukocytes Showing in vitro igG Memory From SARS-CoV-2-Infected Patients

Cited by 3 publications

References 28 publications

Amino Acid Metabolism in Leukocytes Showing In Vitro IgG Memory from SARS-CoV2-Infected Patients

Amino Acid Metabolism in Leukocytes Showing In Vitro IgG Memory from SARS-CoV2-Infected Patients

Amino acids, post-translational modifications, nitric oxide, and oxidative stress in serum and urine of long COVID and ex COVID human subjects

An untargeted metabolomic approach to investigate antiviral defence mechanisms in memory leukocytes secreting anti-SARS-CoV-2 IgG in vitro

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