Decreased serum levels of the inflammaging marker miR-146a are associated with clinical non-response to tocilizumab in COVID-19 patients.
Ontology highlight
ABSTRACT:
SUBMITTER: Sabbatinelli J
PROVIDER: S-EPMC7722494 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundPatients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19.ObjectiveWe sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ.MethodsA retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality.ResultsOne hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients.ConclusionsBaseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.
| S-EPMC7525244 | biostudies-literature
Project description:BackgroundThere is increasing evidence that chronic inflammation is an important determinant in insulin resistance and in the pathogenesis of type 2 diabetes (T2D). MicroRNAs constitute a newly discovered system of cell regulation and in particular two microRNAs (miR-146a and miR-155) have been described as regulators and biomarkers of inflammation.AimTo determine a putative association between the levels of miR-146a and miR-155 in serum of T2D patients, clinical parameters and serological indicators of inflammation.MethodsWe performed quantitative Real Time PCR (qPCR) of microRNAs from serum (56 Ecuadorian T2D ambulatory patients and 40 non-diabetic controls). In addition, we evaluated T2D-related serum cytokines.chemokines and growth factors using a commercially available multi-analyte cytometric bead array system. We correlated outcomes to clinical parameters, including BMI, HbA1c and lipid state.ResultsThe Ecuadorian non-diabetic controls appeared as overweight (BMI>25: patients 85%, controls 82.5%) and as dyslipidemic (hypercholesterolemia: patients 60.7%, controls 67.5%) as the patients. The serum levels of miR-146a were significantly reduced in T2D patients as compared to these non-diabetic, but obese/dyslipidemic control group (mean patients 0.61, mean controls set at 1; p = 0.042), those of miR-155 were normal.The serum levels of both microRNAs correlated to each other (r = 0.478; p<0.001) and to leptin levels. The microRNAs did not correlate to BMI, glycemia and dyslipidemia.From the tested cytokines, chemokines and growth factors, we found IL-8 and HGF significantly raised in T2D patients versus non-diabetic controls (p = 0.011 and 0.023 respectively).ConclusionsThis study shows decreased serum anti-inflammatory miR-146a, increased pro-inflammatory IL-8 and increased HGF (a vascular/insular repair factor) as discriminating markers of failure of glucose control occurring on the background of obesity and dyslipidemia.
| S-EPMC4264887 | biostudies-literature
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.
| S-SCDT-EMM-2021-15227 | biostudies-other
Project description: Not available
| S-EPMC7980142 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 causes substantial morbidity. Tocilizumab, an interleukin-6 receptor antagonist, might improve outcomes by mitigating inflammation. We conducted a retrospective study of patients admitted to the University of Washington Hospital system with COVID-19 and requiring supplemental oxygen. Outcomes included clinical improvement, defined as a two-point reduction in severity on a six-point ordinal scale or discharge, and mortality within 28 days. We used Cox proportional-hazards models with propensity score inverse probability weighting to compare outcomes in patients who did and did not receive tocilizumab. We evaluated 43 patients who received tocilizumab and 45 who did not. Patients receiving tocilizumab were younger with fewer comorbidities but higher baseline oxygen requirements. Tocilizumab treatment was associated with reduced C-reactive protein, fibrinogen, and temperature, but there were no meaningful differences in time to clinical improvement (adjusted hazard ratio [aHR], 0.92; 95% confidence interval [CI], 0.38-2.22) or mortality (aHR, 0.57; 95% CI, 0.21-1.52). A numerically higher proportion of tocilizumab-treated patients had subsequent infections, transaminitis, and cytopenias. Tocilizumab did not improve outcomes in hospitalized patients with COVID-19. However, this study was not powered to detect small differences, and there remains the possibility for a survival benefit.
| S-EPMC7753799 | biostudies-literature
Project description:Background and aimsMicroRNAs (miRNAs) are profoundly involved into the pathophysiology of manifold cancers. Recent data suggested a pivotal role of miRNAs as biomarkers in different biological processes including carcinogenesis. However, their role in neuroendocrine tumors (NETs) is only poorly understood.MethodsWe determined circulating levels of miR-21 and miR-223 in 45 samples from patients with NET treated between 2010 and 2019 at our department and compared them to healthy controls. Results were correlated with clinical records.ResultsIn the total cohort of Patients with NET, miR-223 presented significantly lower levels compared to healthy control samples. In contrast, levels of miR-21 indicated no significant changes between the two groups. Interestingly, despite being significantly downregulated in all NET patients, concentrations of miR-223 were independent of clinical or histopathological factors such as proliferation activity according to Ki-67 index, tumor grading, TNM stage, somatostatin receptor expression, presence of functional/ non-functional disease or tumor relapse. Moreover, in contrast to data from recent publications analyzing other tumor entities, levels of miR-223 serum levels did not reflect prognosis of patients with NET.ConclusionLower concentrations of circulating miR-223 rather reflect the presence of NET itself than certain tumor characteristics. The value of miR-223 as a biomarker in NET might be limited to diagnostic, but not prognostic purposes.
| S-EPMC7775044 | biostudies-literature
Project description:BackgroundCoronavirus disease-19 (COVID-19) spans a wide spectrum of illness. Severe cases of COVID-19 can manifest inflammation in organs other than the lung, in tissues not known to support viral replication, and also in a hypercoagulable state. These observations have suggested that severe acute respiratory syndrome coronavirus 2 can provoke a hyperimmune response in some cases that could lead to secondary organ damage.MethodsWith evidence of elevated levels of interleukin-6 (IL-6) in patients with severe COVID-19, we conducted a small pilot off-label compassionate care study of the IL-6 receptor inhibitor tocilizumab in patients with severe COVID-19.ResultsA single infusion of tocilizumab in patients with severe COVID-19 manifested rapid declines in C-reactive protein and d-dimer and gradual rises in lymphocyte and platelet counts.ConclusionsThese findings suggest both pathophysiological mechanisms and clinical benefit that might be seen with IL-6 inhibition in severe COVID-19.
| S-EPMC7537313 | biostudies-literature
Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.
2022-10-14 | PXD031969 | Pride
Project description:BackgroundC-type natriuretic peptide (CNP) is an endothelium-derived paracrine molecule with an important role in vascular homeostasis. In septic patients, the serum level of the amino-terminal propeptide of CNP (NT-proCNP) shows a strong positive correlation with inflammatory biomarkers and, if elevated, correlates with disease severity and indicates a poor outcome. It is not yet known whether NT-proCNP also correlates with the clinical outcome of patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the current study, we aimed to determine possible changes in the NT-proCNP levels of patients with coronavirus disease 2019 (COVID-19), with special regard to disease severity and outcome.MethodsIn this retrospective analysis, we determined the serum level of NT-proCNP in hospitalized patients with symptoms of upper respiratory tract infection, using their blood samples taken on admission, stored in a biobank. The NT-proCNP levels of 32 SARS-CoV-2 positive and 35 SARS-CoV-2 negative patients were measured to investigate possible correlation with disease outcome. SARS-CoV-2 positive patients were then divided into two groups based on their need for intensive care unit treatment (severe and mild COVID-19).ResultsThe NT-proCNP was significantly different in the study groups (e.g. severe and mild COVID-19 and non-COVID-19 patients), but showed inverse changes compared to previous observations in septic patients: lowest levels were detected in critically ill COVID-19 patients, while highest levels in the non-COVID-19 group. A low level of NT-proCNP on admission was significantly associated with severe disease outcome.ConclusionsLow-level NT-proCNP on hospital admission is associated with a severe COVID-19 disease course. The pathomechanism underlying this observation remains to be elucidated, while future studies in larger patient cohorts are necessary to confirm these observations and reveal therapeutic importance. Trial registration DRKS00026655 Registered 26. November 2021.
| S-EPMC10311835 | biostudies-literature
Project description:SARS-CoV-2 infection shows a wide-ranging clinical severity, requiring prognostic markers. We focused on S100B, a calcium-binding protein present in biological fluids, being a reliable biomarker in disorders having inflammatory processes as common basis and RAGE as main receptor. Since Covid-19 is characterized by a potent inflammatory response also involving RAGE, we tested if S100B serum levels were related to disease severity. Serum samples (n = 74) were collected from hospitalized SARS-CoV-2 positive patients admitted to Covid center. Illness severity was established by admission clinical criteria and Covid risk score. Treatment protocols followed WHO guidelines available at the time. Circulating S100B was determined by ELISA assay. Statistical analysis used Pearson's χ2 test, t-Test, and ANOVA, ANCOVA, Linear Regression. S100B was detected in serum from Covid-19 patients, significantly correlating with disease severity as shown both by the level of intensity of care (p < 0.006) as well by the value of Covid score (Multiple R-squared: 0.3751); the correlation between Covid-Score and S100B was 0.61 (p < 0.01). S100B concentration was associated with inflammation markers (Ferritin, C-Reactive Protein, Procalcitonin), and organ damage markers (Alanine Aminotransferase, Creatinine). Serum S100B plays a role in Covid-19 and can represent a marker of clinical severity in Sars-CoV-2 infected patients.
| S-EPMC7596559 | biostudies-literature