Neuron-specific enolase serum levels in COVID-19 are related to the severity of lung injury

Cione, Erika; Siniscalchi, Antonio; Gangemi, Pietro; Cosco, Lucio; Colosimo, Manuela; Longhini, Federico; Luciani, Filippo; Sarro, Giovambattista De; Berrino, Liberato; D’Agostino, Bruno; Gallelli, Luca

doi:10.1371/journal.pone.0251819

Cited by 22 publications

(30 citation statements)

References 20 publications

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“…So far, modified levels of classic pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), as well as of typical antiinflammatory cytokines such as tumor growth factor β (TGF-β) or IL-10, have been associated with an increased disease severity and risk of mortality [15][16][17]. Furthermore, abnormally increased levels of other soluble inflammatory molecules such as chemokines and growth factors, and of endothelial-and platelet secreted molecules and neuron specific enolase, have been also described in patients with severe COVID-19 [18]. Nevertheless, we still lack a comprehensive analysis of a wide spectrum of IR mediators.…”

Section: Introductionmentioning

confidence: 99%

Impact of the Innate Inflammatory Response on ICU Admission and Death in Hospitalized Patients with COVID-19

et al. 2021

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Objective: To describe the capacity of a broad spectrum of cytokines and growth factors to predict ICU admission and/or death in patients with severe COVID-19. Design: An observational, analytical, retrospective cohort study with longitudinal follow-up. Setting: Hospital Universitario Príncipe de Asturias (HUPA). Participants: 287 patients diagnosed with COVID-19 admitted to our hospital from 24 March to 8 May 2020, followed until 31 August 2020. Main outcome measures: Profiles of immune response (IR) mediators were determined using the Luminex Multiplex technique in hospitalized patients within six days of admission by examining serum levels of 62 soluble molecules classified into the three groups: adaptive IR-related cytokines (n = 19), innate inflammatory IR-related cytokines (n = 27), and growth factors (n = 16). Results: A statistically robust link with ICU admission and/or death was detected for increased serum levels of interleukin (IL)-6, IL-15, soluble (s) RAGE, IP10, MCP3, sIL1RII, IL-8, GCSF and MCSF and IL-10. The greatest prognostic value was observed for the marker combination IL-10, IL-6 and GCSF. Conclusions: When severe COVID-19 progresses to ICU admission and/or death there is a marked increase in serum levels of several cytokines and chemokines, mainly related to the patient’s inflammatory IR. Serum levels of IL-10, IL-6 and GCSF were most prognostic of the outcome measure.

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Section: Introductionmentioning

confidence: 99%

Impact of the Innate Inflammatory Response on ICU Admission and Death in Hospitalized Patients with COVID-19

et al. 2021

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“…Recently, a new clinical marker of lung injury severity and progression of COVID-19 was found, Neuron-Specific Enolase (NSE), which is localized in the cytoplasm of neurons and neuroendocrine cells [ 47 ]. Further studies of interest were the correlation between serum NSE level in the acute phase of COVID patients (who were referred to the emergency department or Intensive Care Unit) and the effects of adaptogens in the same patients in the post-COVID phase.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial

Karosanidze¹,

Kiladze²,

Kirtadze³

et al. 2022

Pharmaceuticals

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Currently, no effective treatment of comorbid complications or COVID-19 long-haulers during convalescence is known. This randomized, quadruple-blind, placebo-controlled trial aimed to assess the efficacy of adaptogens on the recovery of patients with Long COVID symptoms. One hundred patients with confirmed positive SARS-CoV-2 test, discharged from COVID Hotel isolation, Intensive Care Unit (ICU), or Online Clinics, and who experienced at least three of nine Long COVID symptoms (fatigue, headache, respiratory insufficiency, cognitive performance, mood disorders, loss of smell, taste, and hair, sweatiness, cough, pain in joints, muscles, and chest) in the 30 days before randomization were included in the study of the efficacy of Chisan®/ADAPT-232 (a fixed combination of adaptogens Rhodiola, Eleutherococcus, and Schisandra) supplementation for two weeks. Chisan® decreased the duration of fatigue and pain for one and two days, respectively, in 50% of patients. The number of patients with lack of fatigue and pain symptoms was significantly less in the Chisan® treatment group than in the placebo group on Days 9 (39% vs. 57%, pain relief, p = 0.0019) and 11 (28% vs. 43%, relief of fatigue, * p = 0.0157). Significant relief of severity of all Long COVID symptoms over the time of treatment and the follow-up period was observed in both groups of patients, notably decreasing the level of anxiety and depression from mild and moderate to normal, as well as increasing cognitive performance in patients in the d2 test for attention and increasing their physical activity and workout (daily walk time). However, the significant difference between placebo and Chisan® treatment was observed only with a workout (daily walk time) and relieving respiratory insufficiency (cough). A clinical assessment of blood markers of the inflammatory response (C-reactive protein) and blood coagulation (D-dimer) did not reveal any significant difference over time between treatment groups except significantly lower IL-6 in the Chisan® treatment group. Furthermore, a significant difference between the placebo and Chisan® treatment was observed for creatinine: Chisan® significantly decreased blood creatinine compared to the placebo, suggesting prevention of renal failure progression in Long COVID. In this study, we, for the first time, demonstrate that adaptogens can increase physical performance in Long COVID and reduce the duration of fatigue and chronic pain. It also suggests that Chisan®/ADAPT-232 might be useful for preventing the progression of renal failure associated with increasing creatinine.

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“…In addition, several novel biomarkers for differentiating the disease severity of COVID-19 were also studied, for example, serum-neuron-specific enolase (NSE—a pulmonary injury biomarker in lung cancer) [ 101 ], and presepsin (a soluble CD14; a proinflammatory activator of immune cells) [ 102 ]. These biomarkers might be indicators of the differences between some specific characteristics of the patients that might be required for determination.…”

Section: Discussionmentioning

confidence: 99%

“…These biomarkers might be indicators of the differences between some specific characteristics of the patients that might be required for determination. As such, while serum NSE indicates pulmonary involvement in COVID-19 [ 101 ], serum presepsin detects the early onset of sepsis [ 102 ]. Similarly, the detection of the gut permeability defect (or gut-pulmonary axis) might be used to alert physicians to developing severe systemic inflammation in COVID-19 cases, while NETosis biomarkers indicate an initial phase of the systemic responses.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

Saithong

Worasilchai

Saisorn

et al. 2022

Cells

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Due to limited data on the link between gut barrier defects (leaky gut) and neutrophil extracellular traps (NETs) in coronavirus disease 2019 (COVID-19), blood samples of COVID-19 cases—mild (upper respiratory tract symptoms without pneumonia; n = 27), moderate (pneumonia without hypoxia; n = 28), and severe (pneumonia with hypoxia; n = 20)—versus healthy control (n = 15) were evaluated, together with in vitro experiments. Accordingly, neutrophil counts, serum cytokines (IL-6 and IL-8), lipopolysaccharide (LPS), bacteria-free DNA, and NETs parameters (fluorescent-stained nuclear morphology, dsDNA, neutrophil elastase, histone–DNA complex, and myeloperoxidase–DNA complex) were found to differentiate COVID-19 severity, whereas serum (1→3)-β-D-glucan (BG) was different between the control and COVID-19 cases. Despite non-detectable bacteria-free DNA in the blood of healthy volunteers, using blood bacteriome analysis, proteobacterial DNA was similarly predominant in both control and COVID-19 cases (all severities). In parallel, only COVID-19 samples from moderate and severe cases, but not mild cases, were activated in vitro NETs, as determined by supernatant dsDNA, Peptidyl Arginine Deiminase 4, and nuclear morphology. With neutrophil experiments, LPS plus BG (LPS + BG) more prominently induced NETs, cytokines, NFκB, and reactive oxygen species, when compared with the activation by each molecule alone. In conclusion, pathogen molecules (LPS and BG) from gut translocation along with neutrophilia and cytokinemia in COVID-19-activated, NETs-induced hyperinflammation.

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Neuron-specific enolase serum levels in COVID-19 are related to the severity of lung injury

Cited by 22 publications

References 20 publications

Impact of the Innate Inflammatory Response on ICU Admission and Death in Hospitalized Patients with COVID-19

Impact of the Innate Inflammatory Response on ICU Admission and Death in Hospitalized Patients with COVID-19

Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial

Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

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