Association of admission serum levels of neurofilament light chain and in-hospital mortality in geriatric patients with COVID-19

Marchegiani, Francesca; Recchioni, Rina; Marcheselli, Fiorella; Rosa, Mirko Di; Matacchione, Giulia; Giuliani, Angelica; Ramini, Deborah; Stripoli, Pierpaolo; Biscetti, Leonardo; Pelliccioni, Giuseppe; Sarzani, Riccardo; Spannella, Francesco; Cherubini, Antonio; Corsonello, Andrea; Procopio, Antonio Domenico; Bonfigli, Anna Rita; Bonafè, Massimiliano; Lattanzio, Fabrizia; Olivieri, Fabiola

doi:10.1007/s00415-022-11373-8

Cited by 8 publications

(4 citation statements)

References 22 publications

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“…In the attempt to identify soluble markers of the pro-inflammatory/senescent profile at the pre-LD time-point, we assessed the plasma levels of miRNAs associated with inflammation and senescence, namely miR-146a-5p, miR-21-5p, endothelial homeostasis miR-126-3p and B-cell tumor burden miR-150-5p: no significant differences between the two groups of patients were observed ( Figure 2A ). We also assessed the pre-LD plasma levels of senescence-associated cytokines GDF-15 and IL-15, of the myeloid chemokine CXCL-9, as well as of the neuroaxonal damage marker ( 21 ) NfL ( Figures 2B–E ). The plasma level of CXCL-9 was higher in patients who experienced ICANS (mean value [pg/ml]: 10605.50 ± 12639 vs 2140.46 ± 1231.38, p=0.024).…”

Section: Resultsmentioning

confidence: 99%

Peripheral blood cellular profile at pre-lymphodepletion is associated with CD19-targeted CAR-T cell-associated neurotoxicity

et al. 2023

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BackgroundInfusion of second generation autologous CD19-targeted chimeric antigen receptor (CAR) T cells in patients with R/R relapsed/refractory B-cell lymphoma (BCL) is affected by inflammatory complications, such as Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Current literature suggests that the immune profile prior to CAR-T infusion modifies the chance to develop ICANS.MethodsThis is a monocenter prospective study on 53 patients receiving approved CAR T-cell products (29 axi-cel, 24 tisa-cel) for R/R-BCL. Clinical, biochemical, and hematological variables were analyzed at the time of pre-lymphodepletion (pre-LD). In a subset of 21 patients whose fresh peripheral blood sample was available, we performed cytofluorimetric analysis of leukocytes and extracellular vesicles (EVs). Moreover, we assessed a panel of soluble plasma biomarkers (IL-6/IL-10/GDF-15/IL-15/CXCL9/NfL) and microRNAs (miR-146a-5p, miR-21-5p, miR-126-3p, miR-150-5p) which are associated with senescence and inflammation.ResultsMultivariate analysis at the pre-LD time-point in the entire cohort (n=53) showed that a lower percentage of CD3+CD8+ lymphocytes (38.6% vs 46.8%, OR=0.937 [95% CI: 0.882-0.996], p=0.035) and higher levels of serum C-reactive protein (CRP, 4.52 mg/dl vs 1.00 mg/dl, OR=7.133 [95% CI: 1.796-28], p=0.005) are associated with ICANS. In the pre-LD samples of 21 patients, a significant increase in the percentage of CD8+CD45RA+CD57+ senescent cells (median % value: 16.50% vs 9.10%, p=0.009) and monocytic-myeloid derived suppressor cells (M-MDSC, median % value: 4.4 vs 1.8, p=0.020) was found in ICANS patients. These latter also showed increased levels of EVs carrying CD14+ and CD45+ myeloid markers, of the myeloid chemokine CXCL-9, as well of the MDSC-secreted cytokine IL-10. Notably, the serum levels of circulating neurofilament light chain, a marker of neuroaxonal injury, were positively correlated with the levels of senescent CD8+ T cells, M-MDSC, IL-10 and CXCL-9. No variation in the levels of the selected miRNAs was observed between ICANS and no-ICANS patients.DiscussionOur data support the notion that pre-CAR-T systemic inflammation is associated with ICANS. Higher proportion of senescence CD8+ T cells and M-MDSC correlate with early signs of neuroaxonal injury at pre-LD time-point, suggesting that ICANS may be the final event of a process that begins before CAR-T infusion, consequence to patient clinical history.

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Section: Resultsmentioning

confidence: 99%

Peripheral blood cellular profile at pre-lymphodepletion is associated with CD19-targeted CAR-T cell-associated neurotoxicity

et al. 2023

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“…In a NeuroCOVID study, infected patients with severe neurological manifestations (encephalopathy, meningoencephalitis, disrupted movement disorder, or stroke) had increased NFL in the cerebrospinal fluid. Another investigation speculated that serum NFL could be associated with severe outcomes in geriatric patients [60].…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Affects Serum Brain-Derived Neurotrophic Factor and Neurofilament Light Chain in Aged Men: Implications for Morbidity and Mortality

Petrella

Zingaropoli

Ceci

et al. 2023

Cells

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Background and Methods: Severe COVID-19 is known to induce neurological damage (NeuroCOVID), mostly in aged individuals, by affecting brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMP) 2 and 9 and the neurofilament light chain (NFL) pathways. Thus, the aim of this pilot study was to investigate BDNF, MMP-2, MMP-9, and NFL in the serum of aged men affected by COVID-19 at the beginning of the hospitalization period and characterized by different outcomes, i.e., attending a hospital ward or an intensive care unit (ICU) or with a fatal outcome. As a control group, we used a novelty of the study, unexposed age-matched men. We also correlated these findings with the routine blood parameters of the recruited individuals. Results: We found in COVID-19 individuals with severe or lethal outcomes disrupted serum BDNF, NFL, and MMP-2 presence and gross changes in ALT, GGT, LDH, IL-6, ferritin, and CRP. We also confirmed and extended previous data, using ROC analyses, showing that the ratio MMPs (2 and 9) versus BDNF and NFL might be a useful tool to predict a fatal COVID-19 outcome. Conclusions: Serum BDNF and NFL and/or their ratios with MMP-2 and MMP-9 could represent early predictors of NeuroCOVID in aged men.

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“…Interestingly, among classical blood biomarkers, eGFR and NLR represented two strong risk factors of mortality, with eGFR as the risk factor for 31-day mortality, confirming previously results [ 46 ] and NLR representing a risk factor of medium-term death. Previous reports showed that circulating biomarker levels could be negatively related to eGFR, especially in geriatric patients affected by age-related diseases and infectious [ 47 ]. However, this does not preclude the potential role of specific circulating miRNAs in the stratification of geriatric patients based on mortality risk.…”

Section: Discussionmentioning

confidence: 99%

Low circulating levels of miR-17 and miR-126-3p are associated with increased mortality risk in geriatric hospitalized patients affected by cardiovascular multimorbidity

Marchegiani,

Recchioni,

Di Rosa

et al. 2023

GeroScience

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MultiMorbidity (MM), defined as the co-occurrence of two or more chronic conditions, is associated with poorer health outcomes, such as recurrent hospital readmission and mortality. As a group of conditions, cardiovascular disease (CVD) exemplifies several challenges of MM, and the identification of prognostic minimally invasive biomarkers to stratify mortality risk in patients affected by cardiovascular MM is a huge challenge. Circulating miRNAs associated to inflammaging and endothelial dysfunction, such as miR-17, miR-21-5p, and miR-126-3p, are expected to have prognostic relevance. We analyzed a composite profile of circulating biomarkers, including miR-17, miR-21-5p, and miR-126-3p, and routine laboratory biomarkers in a sample of 246 hospitalized geriatric patients selected for cardiovascular MM from the Report-AGE INRCA database and BioGER INRCA biobank, to evaluate the association with all-cause mortality during 31 days and 12 and 24 months follow-up. Circulating levels of miR-17, miR-126-3p, and some blood parameters, including neutrophil to lymphocyte ratio (NLR) and eGFR, were significantly associated with mortality in these patients. Overall, our results suggest that in a cohort of geriatric hospitalized patients affected by cardiovascular MM, lower circulating miR-17 and miR-126-3p levels could contribute to identify patients at higher risk of short- and medium-term mortality.

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Association of admission serum levels of neurofilament light chain and in-hospital mortality in geriatric patients with COVID-19

Cited by 8 publications

References 22 publications

Peripheral blood cellular profile at pre-lymphodepletion is associated with CD19-targeted CAR-T cell-associated neurotoxicity

Peripheral blood cellular profile at pre-lymphodepletion is associated with CD19-targeted CAR-T cell-associated neurotoxicity

COVID-19 Affects Serum Brain-Derived Neurotrophic Factor and Neurofilament Light Chain in Aged Men: Implications for Morbidity and Mortality

Low circulating levels of miR-17 and miR-126-3p are associated with increased mortality risk in geriatric hospitalized patients affected by cardiovascular multimorbidity

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