BACKGROUND:Malnutrition is a prevalent geriatric syndrome, with multifactorial etiology and consequences for health and independence. Inflammation contributes to nutritional decline, yet conventional inflammatory markers often lack sensitivity for identifying malnutrition risk. The soluble receptor for advanced glycation end-products (sRAGE), a modulator of inflammatory responses, has emerged as a biomarker of disease risk and adverse outcomes in various conditions. OBJECTIVES:to evaluate the association between circulating sRAGE levels and nutritional status in community-dwelling older adults. METHODS:This prospective observational study was conducted within the FRASNET cohort. Fifty-two community-dwelling older adults underwent multidimensional geriatric assessments during two time periods: 2017-2020 and 2023-2024. Serum sRAGE levels were measured at both timepoints. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF). Associations between sRAGE and clinical parameters were evaluated through linear regression models adjusted for age and sex. The diagnostic performance of sRAGE in identifying malnutrition was assessed using ROC curve analysis. RESULTS:Higher baseline sRAGE levels were significantly associated with lower BMI (β = -0.003, p = 0.036), reduced calf circumference (β = -0.002, p = 0.04), and poorer nutritional status as revealed by MNA-SF scores (β = -0.001, p = 0.03) at follow-up. Associations were more pronounced in women. ROC analysis indicated good diagnostic accuracy for identifying malnutrition risk, with an AUC of 0.85. The optimal sRAGE cut-off value for malnutrition risk was 1362.5 pg/ml. CONCLUSIONS:Higher sRAGE levels were prospectively associated with poorer nutritional outcomes in older adults, particularly in women. sRAGE may aid early identification of inflammation-related malnutrition risk.

Background: Sarcopenic obesity (SO) affects up to 40% of older adults with obesity, yet many remain protected despite comparable metabolic burden. The molecular basis for this heterogeneity remains unknown. Methods: We exposed seventy-two 12-month-old female mice to high-fat diet (HFD) or standard diet for 7 months. Multi-Omics Factor Analysis integrated muscle transcriptomics and metabolomics to identify latent factors explaining phenotypic variation. Results: Despite uniform obesity development, aging HFD mice showed marked heterogeneity in muscle outcomes. Factor 3 uniquely distinguished dietary groups and predicted muscle dysfunction independent of adiposity severity. Factor 3 revealed metabolic exhaustion: despite coordinated upregulation of fatty acid oxidation genes (Fabp3, Lpl, Acadl) and oxidative markers, long-chain acylcarnitines accumulated and free L-carnitine depleted, indicating incomplete β-oxidation. Concurrent activation of p53, TNF/NFκB, and oxidative stress pathways indicated comprehensive metabolic decompensation. Plasma acetylcarnitine and pantothenol achieved AUC 0.91 for discriminating sarcopenia phenotypes. Conclusions: Individual susceptibility to sarcopenic obesity reflects differential metabolic exhaustion rather than obesity severity, detectable through circulating biomarkers.

BACKGROUND:Mitochondria-derived GDF15 and FGF21, known as mitokines, are emerging biomarkers of metabolic stress and aging-related decline. Their roles in energy balance, inflammation, and muscle metabolism suggest potential for predicting geriatric syndromes, yet prospective evidence is limited. METHODS:Plasma GDF15 and FGF21 and multidimensional geriatric assessment at baseline and at 6-year follow-up in 52 community-dwelling adults aged ≥ 65 years from the FRASNET cohort. RESULTS:Over a six-year follow-up, participants exhibited signs of functional decline, including increased waist circumference, greater fatigue severity, and higher medication use. FGF21 levels declined significantly over time (p = 0.03), whereas GDF15 levels remained stable. Higher baseline GDF15 levels identified individuals at higher risk to become frail (AUC= 0.85 with Fried Phenotype and AUC= 0.96 with Clinical Frailty Scale) or malnourished (AUC=0.94) and at risk to fall (AUC=0.98). FGF21 associated to malnutrition (AUC=0.98). GDF15 prospectively associated to high risk of frailty and negatively associated with physical performance and nutritional status after six years. CONCLUSIONS:In this cohort, higher baseline levels of GDF15 and FGF21 were associated with the risk to become frail or malnourished. These findings support the integration of mitokines into early risk stratification tools for older adults. Further validation in larger cohorts is warranted.

Background: Acute sarcopenia refers to the swift decline in muscle function and mass following acute events such as illness, surgery, trauma, or burns that presents significant challenges in hospitalized older adults. Methods: narrative review to describe the mechanisms and management of acute sarcopenia. Results: The prevalence of acute sarcopenia ranges from 28% to 69%, likely underdiagnosed due to the absence of muscle mass and function assessments in most clinical settings. Systemic inflammation, immune–endocrine dysregulation, and anabolic resistance are identified as key pathophysiological factors. Interventions include early mobilization, resistance exercise, neuromuscular electrical stimulation, and nutritional strategies such as protein supplementation, leucine, β-hydroxy-β-methyl-butyrate, omega-3 fatty acids, and creatine monohydrate. Pharmaceuticals show variable efficacy. Conclusions: Future research should prioritize serial monitoring of muscle parameters, identification of predictive biomarkers, and the involvement of multidisciplinary teams from hospital admission to address sarcopenia. Early and targeted interventions are crucial to improve outcomes and prevent long-term disability associated with acute sarcopenia.

Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, and with a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12 months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis.

Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology. Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models. Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ2 = 4.66, p = 0.031) and anxiety (χ2 = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months. A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.

IntroductionSARS-CoV-2 mRNA vaccinations elicit both virus-specific humoral and T-cell responses, but a complex interplay of different influencing factors, such as natural immunity, gender, and age, guarantees host protection. The present study aims to assess the immune dynamics of humoral, T-cell response, and influencing factors to stratify individual immunization status up to 10 months after Comirnaty-vaccine administration.MethodsTo this aim, we longitudinally evaluated the magnitude and kinetics of both humoral and T-cell responses by serological tests and enzyme-linked immunospot assay at 5 time points. Furthermore, we compared the course over time of the two branches of adaptive immunity to establish an eventual correlation between adaptive responses. Lastly, we evaluated putative influencing factors collected by an anonymized survey administered to all participants through multiparametric analysis. Among 984 healthcare workers evaluated for humoral immunity, 107 individuals were further analyzed to describe SARS-CoV-2-specific T-cell responses. Participants were divided into 4 age groups: <40 and ≥40 years for men, <48 and ≥48 years for women. Furthermore, results were segregated according to SARS-CoV-2-specific serostatus at baseline.ResultsThe disaggregated evaluation of humoral responses highlighted antibody levels decreased in older subjects. The humoral responses were higher in females than in males (p=0.002) and previously virus-exposed subjects compared to naïve subjects (p<0.001). The vaccination induced a robust SARS-CoV-2 specific T-cell response at early time points in seronegative subjects compared to baseline levels (p<0.0001). However, a contraction was observed 6 months after vaccination in this group (p<0.01). On the other hand, the pre-existing specific T-cell response detected in natural seropositive individuals was longer-lasting than the response of the seronegative subjects, decreasing only 10 months after vaccination. Our data suggest that T-cell reactiveness is poorly impacted by sex and age. Of note, SARS-CoV-2-specific T-cell response was not correlated to the humoral response at any time point.DiscussionThese findings suggest prospects for rescheduling vaccination strategies by considering individual immunization status, personal characteristics, and the appropriate laboratory tests to portray immunity against SARS-CoV-2 accurately. Deepening our knowledge about T and B cell dynamics might optimize the decision-making process in vaccination campaigns, tailoring it to each specific immune response.

Immunological consequences of endoscopic ultrasound (EUS)-local thermal ablation (LTA) for pancreatic ductal adenocarcinoma (PDAC) have not been extensively assessed. We aimed to explore EUS-LTA effects on the systemic immune response in PDAC. Peripheral blood was collected from 10 treatment-naïve patients with borderline resectable and locally advanced PDAC, randomly allocated to Nab-paclitaxel plus Gemcitabine chemotherapy (CT-arm, n = 5) or EUS-LTA with HybridTherm Probe plus CT (HTP + CT-arm, n = 5). Twenty healthy donors were included as controls. Flow-cytometry and multiplex assays were used to profile immune cell subsets and measure serum cytokines/chemokines, respectively. At baseline, PDAC patients showed increased circulating monocytes and lower circulating lymphocytes and CD19+ B cells counts compared to healthy controls. After 4 months, CT induced decrease of B regulatory cells, CD4+ cytotoxic T cells and IL-1β. The addition of EUS-HTP to CT selectively decreased the serum levels of APRIL/TNFSF13 as well as T regulatory cells, total, classic and inflammatory monocytes. Serum levels of APRIL/TNFSF13 and total, classic and inflammatory monocytes counts at baseline were associated with worse overall survival. EUS-HTP has the potential to selectively impact on immune cells and cytokines associated with poor outcomes in PDAC.

BackgroundChromogranin A (CgA) and its fragment vasostatin I (VS-I) are secreted in the blood by endocrine/neuroendocrine cells and regulate stress responses. Their involvement in Coronavirus 2019 disease (COVID-19) has not been investigated. MethodsCgA and VS-I plasma concentrations were measured at hospital admission from March to May 2020 in 190 patients. 40 age- and sex-matched healthy volunteers served as controls. CgA and VS-I levels relationship with demographics, comorbidities and disease severity was assessed through Mann Whitney U test or Spearman correlation test. Cox regression analysis and Kaplan Meier survival curves were performed to investigate the impact of the CgA and VS-I levels on in-hospital mortality. ResultsMedian CgA and VS-I levels were higher in patients than in healthy controls (CgA: 0.558 nM [interquartile range, IQR 0.358-1.046] vs 0.368 nM [IQR 0.288-0.490] respectively, p = 0.0017; VS-I: 0.357 nM [IQR 0.196-0.465] vs 0.144 nM [0.144-0.156] respectively, p<0.0001). Concentration of CgA, but not of VS-I, significantly increased in patients who died (n = 47) than in survivors (n = 143) (median 0.948 nM [IQR 0.514-1.754] vs 0.507 nM [IQR 0.343-0.785], p = 0.00026). Levels of CgA were independent predictors of in-hospital mortality (hazard ratio 1.28 [95% confidence interval 1.077-1.522], p = 0.005) when adjusted for age, number of comorbidities, respiratory insufficiency degree, C-reactive protein levels and time from symptom onset to sampling. Kaplan Meier curves revealed a significantly increased mortality rate in patients with CgA levels above 0.558 nM (median value, log rank test, p = 0.001). ConclusionPlasma CgA levels increase in COVID-19 patients and represent an early independent predictor of mortality.

Abstract Background Pentraxin 3 (PTX3) is an acute phase protein, which regulates the outcomes of inflammation. Currently, there are no myocarditis-typical biomarkers that allow a non-invasive diagnosis, and endomyocardial biopsy (EMB) is still the gold standard. Finally, risk stratification is often challenging in these patients. Aim To investigate whether PTX3 could be expressed in cardiomyocytes and released during myocarditis, serving as a novel and independent diagnostic indicator of myocardial inflammation, and contributing to prognosis prediction. Methods Fifty-five patients with a diagnosis of acute or chronic active myocarditis proven by cardiac magnetic resonance (CMR) and/or endomyocardial biopsy (EMB), were included. First, we evaluated tissue PTX3 expression by immunohistochemistry (IHC). Then, we assessed circulating blood PTX3 by ELISA technique. Results On cardiac tissue, PTX3 at IHC did not localize in the interstitium, and showed an inconstant expression in the vascular endothelium, but a marked staining by cardiomyocytes in all myocarditis patients. The only exception was represented by two patients with systemic COVID-19, with SARS-CoV-2 and PVB-19 intracardiac genomes, respectively, who showed a diffuse cardiac PTX3 expression. Remarkably, at semi-quantitative pixel analysis, viral aetiology showed higher levels of tissue expression, rather than the autoimmune one. Circulating PTX3 levels were significantly higher in myocarditis patients than controls, with pathologic values in 87% of myocarditis patients, and none among controls. Remarkably, plasma PTX3 proved to be more sensitive in myocarditis detection than CRP, ESR, troponin T, and NT-proBNP. As regards of prognosis, we observed that patients with heart failure (HF) presentation all had elevated PTX3 levels, as compared with chest pain or arrhythmia. Remarkably, patients with reduced LVEF (<50%) at admission who recovered during follow-up had higher baseline PTX3 levels, rather than those whose systolic function did not improve. Conclusions Tissue PTX3 is mostly expressed by cardiomyocytes in patients with active myocarditis on EMB samples. In addition, plasma PTX3 is a sensitive diagnostic and prognostic marker in patients with inflammatory cardiomyopathy.

OBJECTIVES:We performed a retrospective and prospective observational study to investigate whether the T lymphocyte activation antigen dipeptidyl peptidase 4 (DPP4)/CD26 is expressed in the skeletal muscle of patients with idiopathic inflammatory myopathies (IIM) and whether its expression offers clues to understand the events taking place in the tissue.METHODS:CD26 expression in the muscle, evaluated by immunofluorescence, was assessed in 32 patients with IIM and 5 healthy controls and compared among patients with dermatomyositis (DM), immune-mediated necrotising myopathy (IMNM), inclusion body myositis (IBM), and polymyositis (PM). The relationship of CD26 expression and localization with clinical, serological and histological features was determined.RESULTS:CD26 is selectively expressed in the skeletal muscle of patients with IIM. The highest levels of CD26 are found in the skeletal muscle from patients with DM and in particular in those characterized by tissue necrosis and vascular inflammation. CD26 expression is associated with decreased muscle performance and independently predicts the number of treatments before reaching disease stabilization or improvement (odds ratio, OR=1.2, p<0.05).CONCLUSIONS:CD26 is expressed in the IIM skeletal muscle and may represent a target of molecular intervention for patients with treatment-refractory myositis.

Calcium dobesilate (CaD) is used for the treatment of diabetic retinopathy and nephropathy. This agent exerts antioxidant effects. In the present study, we evaluated the protective effects of oral administration of CaD against hepatorenal damages in a mice model of aging induced by d-galactose (d-gal). We used 28 male albino mice, which equally and randomly were divided into four groups as follows: intact, aging (d-gal at the dose of 500 mg/kg, p.o.), aging + CaD 50 (d-gal plus CaD at the dose of 50 mg/kg), and aging + CaD 100 (d-gal plus CaD at the dose of 100 mg/kg, p.o.). All drugs were administered orally once a day for 42 days. The liver and kidney damages were evaluated by measuring mass indices, levels of serum creatinine and blood urea nitrogen, and activities of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and by histopathological evaluation. Moreover, hepatic and renal tissue oxidant/antioxidant markers (malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase) were measured. The results showed that d-gal treatment induced significant oxidative stress in the kidney and liver that was paralleled by dysfunctions and histological alterations of these organs. CaD significantly improved the liver and kidney indices, implemented functional capacity of the liver and kidney, as well as decreased oxidative stress enhancing antioxidative enzyme activities. CaD treatment also inhibited the development of histological alterations of both kidney and liver. CaD might represent a promising therapeutic agent for the attenuation of hepatorenal injuries induced by aging.

Abstract Background Pentraxin-3 (PTX3) is an acute phase protein, which plays pivotal roles in innate immunity and inflammation. Among cardiovascular diseases, PTX3 was found to be elevated in acute myocardial infarction, chronic heart failure, and cardiac arrest. So far, however, PTX3 has never been investigated in the context of myocarditis. Purpose To evaluate PTX3 as a circulating marker of inflammation in patients with suspected myocarditis. Methods We enrolled 30 consecutive inpatients with new diagnosis of myocarditis, proven both by the updated Lake Louise criteria on cardiac magnetic resonance (CMR), and by the Dallas criteria on endomyocardial biopsy (EMB) (100%). Circulating serum PTX3 was assessed at the time of EMB, by ELISA technique using a commercial kit. Normal values for PTX3 were considered as <2 ng/mL, as in previous studies. A normal control group (n=10) was used for results validation of PTX3. Results In our cohort (77% males, age 50±18 y; median left ventricle ejection fraction [LVEF] 50%, IQR 30–59%), PTX3 levels were assessed in 30 patients. PTX3 levels were elevated in 26/30 (87%) patients with myocarditis (median 4,36 ng/mL, IQR 2,44–6,72, range 1,20–40,0), and in none (0/10) among healthy controls (median 1,28 ng/mL, IQR 1,04–1,36, range 0,77–1,94) (p=0,001). In the study group, the yield of other cardiac biomarkers was lower: 12/30 (40%) for C-reactive protein, 23/30 (77%) for T-troponin, and 20/30 (67%) for NTproBNP. PTX3 was constantly elevated in patients presenting with heart failure (HF) (16/16, 100%), compared with those presenting with acute coronary syndrome-like (8/10, 80%), or arrhythmias (2/4, 50%) (p=0,024). In particular, elevated PTX3 was associated with systolic dysfunction (LVEF <50%) at discharge (16/16 vs. 10/14, p=0,022). Conclusion Our preliminary data suggest PTX3 as a novel biomarker with potential diagnostic and prognostic value for myocarditis and inflammatory cardiomyopathy. Funding Acknowledgement Type of funding sources: None.

Infectious and inflammatory stimuli elicit the generation of chitinase-3-like protein-1 (CHI3L1), involved in tissue damage, repair and remodeling. We evaluated whether plasma CHI3L1 at disease onset predicts clinical outcome of patients with Coronavirus 2019 (COVID-19) disease. Blood from 191 prospectively followed COVID-19 patients were collected at hospital admission between March 18th and May 5th, 2020. Plasma from 80 survivors was collected one month post-discharge. Forty age- and sex-matched healthy volunteers served as controls. Primary outcome was transfer to intensive care unit (ICU) or death. CHI3L1 was higher in COVID-19 patients than controls ( p < 0.0001). Patients with unfavorable outcome (41 patients admitted to ICU, 47 died) had significantly higher CHI3L1 levels than non-ICU survivors ( p < 0.0001). CHI3L1 levels abated in survivors one month post-discharge, regardless of initial disease severity ( p < 0.0001), although remaining higher than controls ( p < 0.05). Cox regression analysis revealed that CHI3L1 levels predict primary outcome independently of age, sex, comorbidities, degree of respiratory insufficiency and systemic inflammation or time from symptom onset to sampling ( p < 0.0001). Kaplan–Meier curve analysis confirmed that patients with CHI3L1 levels above the median (361 ng/mL) had a poorer prognosis (log rank test, p < 0.0001). Plasma CHI3L1 is increased in COVID-19 patients and predicts adverse outcome.

Calcium dobesilate (CaD) is an established vasoactive and angioprotective drug commonly used for the clinical treatment of diabetic retinopathy and chronic venous insufficiency. It has antioxidant properties and controls vascular permeability. In the current study, we explored the possible role of CaD against anxiety and cognitive dysfunction as well as against oxidative brain damage induced by D-gal treatment in mice. D-galactose (D-gal) long-term treatment in mice induces the overproduction of reactive oxygen species (ROS) and is a well-accepted experimental model of oxidative stress-linked cognitive disorders in physiological aging. CaD was administered (50 and 100 mg/kg/day p.o.) in male mice treated with D-gal (500 mg/kg/day p.o.) for six weeks. Thereafter, animals were behaviorally assessed in elevated plus-maze, Y-maze, and shuttle box tests, and brains were dissected for further biochemical analysis. Results demonstrated that bodyweight loss and cognitive impairments of D-gal-treated animals were reversed by CaD administration as evaluated by the measurement of mice performance. CaD treatment also inhibited brain oxidative stress in aging mouse by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities. With the animal model's limitation, our results suggest that CaD, which is already approved for clinical use and safe, could be an interesting pharmacological tool to reduce or prevent age-related behavioral and brain oxidative stress conditions. These results could open new perspectives for the clinical use of CaD in counteracting brain oxidative stress and preventing cognitive impairment in aging.

Les traitements correcteurs de certains effets secondaires neurologiques induits par les traitements antipsychotiques peuvent être à l'origine d'effets indésirables de type anticholinergiques. Cependant, le risque de survenue ou d'exacerbation de symptômes psychotiques induits par ces traitements est beaucoup moins connu avec seulement quelques cas publiés concernant la tropatépine. De plus, les recommandations d'utilisation de ces traitements restent imprécises, aussi bien concernant leur indication que concernant leur effets indésirables, anticholinergiques ou non.Nous rapportons le cas d'un épisode psychotique chez un patient de 18 ans potentiellement acutisé suite à une intoxication médicamenteuse volontaire par la tropatépine.À dose élevée, les traitements anticholinergiques, tropatépine incluse, pourraient induire l'exacerbation d'épisodes psychotiques. De plus, les données épidémiologiques disponibles mettent en évidence une prescription inadaptée et excessive de ces traitements. Leur utilisation et leurs risques devraient être mieux connus des praticiens et nécessitent une mise à jour des recommandations disponibles.Corrective treatments for some neurological side effects due to antipsychotic treatments can induce anticholinergic adverse effects. However, the risk of triggering or increasing psychotic symptoms induced by these drugs is unknown with only one case-report concerning the tropatepine. In addition, recommendations for the use of these drugs remain imprecise regarding the management of this type of adverse effect.We report the case of a psychotic episode in an 18-year-old patient potentially acutised after an auto-intoxication with tropatepine.At high doses, anticholinergic treatments, including tropatepine, might increase psychotic episodes. In addition, the available epidemiological data reveal an inappropriate and excessive prescription of these drugs. Their use and risks should be better known and need an update of the available recommendations.

Aim: Obesity is a risk factor for COVID-19, but the underlying mechanisms are unclear. We investigated the role of adiponectin (an anti-inflammatory adipokine), leptin (a pro-inflammatory adipokine) and their ratio (Adpn/Lep) in this context. Design: Single-centre, prospective observational study. Methods. Adiponectin and leptin were measured in 60 COVID-19 patients with mild (not hospitalised, n=11), moderate (hospitalised but not requiring intensive care, n=25) and severe (admission to the intensive care unit [ICU] or death, n=24) disease. Results: Adiponectin and leptin levels were similar across severity groups, but patients with moderate severity had the highest Adpn/Lep ratio (1.2 [0.5; 2.0], 5.0 [1.6; 11.2], 2.1 [1.0; 3.6] in mild, moderate and severe disease; P = 0.019). Adpn/Lep, but not adiponectin or leptin alone, correlated with systemic inflammation (C reactive protein, CRP: Spearman's rho 0.293, P = 0.023). When dividing patients into Adpn/Lep tertiles, adiponectin was highest, whereas leptin was lowest in the third (highest) tertile. Patients in the highest Adpn/Lep tertile had numerically lower rates of obesity, diabetes and hypertension, and lower rates of death or admission to ICU versus other tertiles. At linear regression in the whole cohort, CRP significantly predicted Adpn/Lep (beta 0.291, P = 0.022), while female gender (beta -0.289, P = 0.016), diabetes (beta -0.257, P = 0.028), and hypertension (beta -239, P = 0.043) were negative predictors. Conclusions: We speculate that the rise in Adpn/Lep, due to increased adiponectin and reduced leptin, is a compensatory response to systemic inflammation. In patients with worse cardiometabolic health (e.g. diabetes, hypertension) this mechanism might be blunted, possibly contributing to higher mortality. (C) 2021 Elsevier Masson SAS. All rights reserved.

Background Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. Methods We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. Results Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233–0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547–0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. Conclusions CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19. Graphic abstract