Metabolic snapshot of plasma samples reveals new pathways implicated in SARS-CoV-2 pathogenesis

Albóniga, Oihane E.; Jiménez, Daniel; Sánchez-Conde, Matilde; Vizcarra, Pilar; Ron, Raquel; Herrera, Sabina; Martínez-Sanz, Javier; Moreno, Elena; Moreno, Santiago; Barbas, Coral; Serrano‐Villar, Sergio

doi:10.1101/2021.09.29.462326

Cited by 4 publications

(5 citation statements)

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“…Exercising due caution due to the severity of the disease, a recent study conducted on hospitalized SARS-CoV-2 patients revealed an association between mortality and concurrent abnormalities in NLR and ADMA [45]. This supports the prognostic value of ADMA assessments in these patients, both during hospitalization and throughout the post-COVID syndrome period, which is still not fully understood [46][47][48][49][50]. Although none of our patients had diabetes, we did not conduct HOMA testing.…”

Section: Discussionsupporting

confidence: 57%

Neutrophil-lymphocyte ratio and update conclusions from a 2-year double-blind rct testing fermented papaya preparation in healthy middle-aged/elderly subjects

Lorenzetti,

Ayala,

et al. 2024

FFS

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Background:T his study represents the second part of a 2-year interventional study in middle-aged /elderly healthy subjects treated either with an antioxidant supplementation (200mg trans-resveratrol, 100mg Centella asiatica extract, 80mg ubiquinol, 50mg epigallo-cathechin-gallate, 20 mg anthocyanidins, 5mg zinc, and 200 IU vitamin E) or with a proprietary fermented papaya preparation (FPP). The choice of the fermented papaya preparation was based on over 12 years of experimental and clinical data proving its effectiveness on redox and immune regulation. The aim of this study was to complete a 24-month investigation of the potential beneficial effect of this functional food on key age-related immune system parameters.Methods: Study population: From a total of 106 subjects, we analyzed data collected from ninety-eight clinically stable, healthy community dwelling males and females aged 58 to 76 years. The investigation followed a double-blind methodology involving two groups, A and B. Group A received FPP® 4.5 grams, one sachet twice a day, coupled with a placebo capsule in the morning. Meanwhile, Group B was administered a papaya-flavored sachet twice a day, with an additional antioxidant mixture capsule in the morning, referred to as the AA group. Morning blood samples were collected and tested for: Asymmetric dimethylarginine (ADMA), apoptosis of PBMCs and blood including Neutrophil-Lymphocyte Ratio (NLR) after 12 months, i.e. corresponding to 24 months of the 2-year study (Visit VI of the initial protocol). Results: As compared to the first preliminary published year of the study, this further 12-month study enabled a more comprehensive analysis with a significant increase of analyzed overweight (≥25 and ≤29.9 kg/m2) subjects (58 vs 31, P<0.05). On the 24-month mark, AA-group showed a significant increase of NLR (P<0.05 vs entry level and FPP group), whereas FPP-group maintained a stable value. Urinary 8-OHdG values maintained, as in the preliminary study, a wide dispersion of data but both treatments equally reduced its value in over 27BMI/r over 70y old subjects, which as taken separately, had significantly elevated values (p<0.05 vs younger subjects). ADMA and frequency of apoptotic cells values were beneficially reduced only by FPP supplementation throughout all 24 months of the study (P<0.05 vs baseline and vs AA supplementation). A significant correlation between NLR and Apoptosis of PBMCs appeared in FPP-treated subjects and this was more pronounced in subjects with >27BMI or over 70 years of age.Conclusions: The novelty of the present work was the finding that FPP represents a substantial pharma-grade, non-GMO technological advancement over uncontrolled traditional plant extracts. This functional food affects oxi-inflammatory aging phenotype and NLR, a marker worth great attention for its preventive interventional potential in middle-age/elderly communities health care. Keywords: Fermented Papaya Preparation, NLR, ADMA, apoptosis, antioxidants, SARS-Cov19

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Section: Discussionsupporting

confidence: 57%

Neutrophil-lymphocyte ratio and update conclusions from a 2-year double-blind rct testing fermented papaya preparation in healthy middle-aged/elderly subjects

Lorenzetti,

Ayala,

et al. 2024

FFS

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“…For example, RNA viruses such as rhinovirus [49], influenza virus [50], Zika virus [51], Dengue virus [52], hepatitis C virus [53], and human immunodeficiency virus [54] can hijack the TCA cycle during viral replication. Recent studies have established methods for studying the metabolomics of SARS-CoV-2 infection [55][56][57][58]. However, detailed downstream analysis and the role of the identified host pathways during viral replication were not fully investigated.…”

Section: Discussionmentioning

confidence: 99%

Targeting ACLY efficiently inhibits SARS-CoV-2 replication

Yuen¹,

Chan²,

Yan³

et al. 2022

Int. J. Biol. Sci.

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The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment targets. In this study, we dissected the metabolome derived from COVID-19 patients to identify key host factors that are required for efficient SARS-CoV-2 replication. Through a series of metabolomic analyses, in vitro, and in vivo investigations, we identified ATP citrate lyase (ACLY) as a novel host factor required for efficient replication of SARS-CoV-2 wild-type and variants, including Omicron. ACLY should be further explored as a novel intervention target for COVID-19.

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“…Dataset III (dataset from Spain) consisted of plasma samples from COVID-19 patients (n = 254) diagnosed by RT-PCR and the group of healthy volunteers (n = 133) with a negative COVID-19 test result [23]. RT-PCR.…”

Section: Dataset III (Spain Dataset): Lc-ms Analysismentioning

confidence: 99%

“…COVID-19 patients were grouped into the following categories: (i) severe COVID-19: patients who developed severe respiratory syndrome; (ii) moderate COVID-19: patients who have opportunities on chest X-rays and in need of oxygen therapy, (iii) mild COVID-19: patients who were asymptomatic one week after infection with SARS-CoV-2, and who also did not need oxygen therapy. All samples were analyzed by capillary electrophoresis coupled by time-of-ight mass spectrometer (CE-MS), with an electrospray analyzer [23]. The median age of the healthy group was lower [42 patients there was no signi cant difference (52%).…”

Section: Dataset III (Spain Dataset): Lc-ms Analysismentioning

confidence: 99%

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Novel COVID-19 biomarkers identified through multi-omics data analysis: N-acetyl-4-O-acetylneuraminic acid, N-acetyl-L-alanine, N-acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate

de Fátima Cobre,

Alves,

Gotine

et al. 2024

Intern Emerg Med

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Introduction: Apply machine learning models to identify new biomarkers associated with the early diagnosis and prognosis of SARS-CoV-2 infection, aiming to prevent long COVID.Material and methods: Plasma and serum samples from COVID-19 patients (mild, moderate, and severe), patients with other pneumonias (but with negative COVID-19 RT-PCR) and from healthy volunteers (control), from hospitals in four different countries (China, Spain, France, and Italy) were analyzed by GC-MS, LC -MS and NMR. Machine learning models (PCA and PLS-DA) were developed for predicting the diagnosis and prognosis of COVID-19 and identifying biomarkers associated with these outcomes.Results. A total of 1410 patient samples were analyzed. In all analyzed data, the PLS-DA model presented a diagnostic and prognostic accuracy of around 95%. A total of 23 biomarkers (e.g. spermidine, taurine, L-aspartic, L-glutamic, L-phenylalanine and xanthine, ornithine and ribothimidine) have been identi ed as being associated with the diagnosis and prognosis of COVID-19. Additionally, we also identi ed for the rst time six new biomarkers (N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine and glycerol 1-myristate) that are also associated with the severity and diagnosis of COVID-19. These six new biomarkers were elevated in severe COVID-19 patients when compared to patients with mild disease or healthy volunteers. Conclusion:The PLS-DA model was able to miss the diagnosis and prognosis of COVID-19 around 95%. We also identi ed six new biomarkers that were increased in plasma and serum of COVID-19 patients (N-Acetyl-4-O-acetylneuraminic acid, N-Acetyl-L-Alanine, N-Acetyltriptophan, palmitoylcarnitine and glycerol 1-myristate) and should be deeply evaluated as prognostic and diagnostic indicators of COVID-19.

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Metabolic snapshot of plasma samples reveals new pathways implicated in SARS-CoV-2 pathogenesis

Cited by 4 publications

References 54 publications

Neutrophil-lymphocyte ratio and update conclusions from a 2-year double-blind rct testing fermented papaya preparation in healthy middle-aged/elderly subjects

Neutrophil-lymphocyte ratio and update conclusions from a 2-year double-blind rct testing fermented papaya preparation in healthy middle-aged/elderly subjects

Targeting ACLY efficiently inhibits SARS-CoV-2 replication

Novel COVID-19 biomarkers identified through multi-omics data analysis: N-acetyl-4-O-acetylneuraminic acid, N-acetyl-L-alanine, N-acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate

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