Neopterin: A Promising Candidate Biomarker for Severe COVID-19

Hailemichael, Wasihun; Kiros, Mulugeta; Akelew, Yibeltal; Getu, Sisay; Henok, Andualem

doi:10.2147/jir.s290264

Cited by 18 publications

(18 citation statements)

References 56 publications

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“…Moreover, considering that, as mentioned above, neopterin is recognized as an expedient biomarker for immune system activation, including monocytes and dendritic cells responsible for the de novo expression of iNOS, our protocols can be assumed to be able to positively impact post viral rehabilitations programs [63,64].…”

Section: Discussionmentioning

confidence: 99%

Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study

Balestra

Lambrechts

Mrakic‐Sposta

et al. 2021

IJMS

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Inflammation is an adaptive response to both external and internal stimuli including infection, trauma, surgery, ischemia-reperfusion, or malignancy. A number of studies indicate that physical activity is an effective means of reducing acute systemic and low-level inflammation occurring in different pathological conditions and in the recovery phase after disease. As a proof-of-principle, we hypothesized that low-intensity workout performed under modified oxygen supply would elicit a “metabolic exercise” inducing a hormetic response, increasing the metabolic load and oxidative stress with the same overall effect expected after a higher intensity or charge exercise. Herein, we report the effect of a 5-week low-intensity, non-training, exercise program in a group of young healthy subjects in combination with the exposure to hyperoxia (30% and 100% pO2, respectively) or light hypoxia (15% pO2) during workout sessions on several inflammation and oxidative stress parameters, namely hemoglobin (Hb), redox state, nitric oxide metabolite (NOx), inducible nitric oxide synthase (iNOS), inflammatory cytokine expression (TNF-α, interleukin (IL)-6, IL-10), and renal functional biomarkers (creatinine, neopterin, and urates). We confirmed our previous reports demonstrating that intermittent hyperoxia induces the normobaric oxygen paradox (NOP), a response overlapping the exposure to hypoxia. Our data also suggest that the administration of modified air composition is an expedient complement to a light physical exercise program to achieve a significant modulation of inflammatory and immune parameters, including cytokines expression, iNOS activity, and oxidative stress parameters. This strategy can be of pivotal interest in all those conditions characterized by the inability to achieve a sufficient workload intensity, such as severe cardiovascular alterations and articular injuries failing to effectively gain a significant improvement of physical capacity.

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Section: Discussionmentioning

confidence: 99%

Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study

Balestra

Lambrechts

Mrakic‐Sposta

et al. 2021

IJMS

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“…Neopterin measurement at hospital admission, identifying patients at risk of a severe disease course (high neopterin levels, >53nM), can serve as an urgently required tool to guide the triage of infected patients and ensure that critical care beds and specialized hospital wards are dedicated to their treatment ( Hailemichael et al., 2021 ). In doing so, healthcare resources will be put to best use during pandemic peak periods and the pressure on specialized hospital wards will be reduced.…”

Section: Discussionmentioning

confidence: 99%

“…Neopterin may therefore serve both as a biomarker of an early inflammatory state based on IFN-γ signaling, which should be associated with a large quantity of surface bound TNF-α ready for secretion upon an acute event, such as viral infection and ADAM17 induction. This therefore suggests that high neopterin levels may be associated with a high risk of developing an intense inflammatory reaction, such as the cytokine storm observed in the late phase of severe SARS-CoV-2 infection ( Hailemichael et al., 2021 ). Distinct cytokine profiles have been described to be associated with COVID-19 severity and differentially predictive of mortality according to oxygen support modalities ( Dorgham et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients

Chauvin

Larsen

Quirant

et al. 2021

Front. Cell. Infect. Microbiol.

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HighlightsInnate immune activation during Covid-19 infection is associated with pernicious clinical outcome.BackgroundCoronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity.MethodsWe measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death.ResultsSevere and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity.ConclusionWe propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.

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“…A high level of blood Nep (> 50 nm) is indicative of high fatal risks for patients with COVID-19 [ 108 ]. Nep is helpful for early prediction of COVID-19 severity and can serve as a prognostic marker [ 109 ]. Patients with COVID-19 do have neurologic symptoms, but the origin of central nervous system pathogenesis is unclear.…”

Section: Different Oxidation States Relate To Different Biological Ro...mentioning

confidence: 99%

Insights into Molecular Structure of Pterins Suitable for Biomedical Applications

Buglak

Kapitonova

Vechtomova

et al. 2022

IJMS

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Pterins are an inseparable part of living organisms. Pterins participate in metabolic reactions mostly as tetrahydropterins. Dihydropterins are usually intermediates of these reactions, whereas oxidized pterins can be biomarkers of diseases. In this review, we analyze the available data on the quantum chemistry of unconjugated pterins as well as their photonics. This gives a comprehensive overview about the electronic structure of pterins and offers some benefits for biomedicine applications: (1) one can affect the enzymatic reactions of aromatic amino acid hydroxylases, NO synthases, and alkylglycerol monooxygenase through UV irradiation of H4pterins since UV provokes electron donor reactions of H4pterins; (2) the emission properties of H2pterins and oxidized pterins can be used in fluorescence diagnostics; (3) two-photon absorption (TPA) should be used in such pterin-related infrared therapy because single-photon absorption in the UV range is inefficient and scatters in vivo; (4) one can affect pathogen organisms through TPA excitation of H4pterin cofactors, such as the molybdenum cofactor, leading to its detachment from proteins and subsequent oxidation; (5) metal nanostructures can be used for the UV-vis, fluorescence, and Raman spectroscopy detection of pterin biomarkers. Therefore, we investigated both the biochemistry and physical chemistry of pterins and suggested some potential prospects for pterin-related biomedicine.

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Neopterin: A Promising Candidate Biomarker for Severe COVID-19

Cited by 18 publications

References 56 publications

Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study

Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study

Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients

Insights into Molecular Structure of Pterins Suitable for Biomedical Applications

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