Elevated interleukin-6 is associated with severity of COVID-19: A meta-analysis.
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ABSTRACT:
SUBMITTER: Zhu J
PROVIDER: S-EPMC7283812 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and Objectives: Procalcitonin (PCT) is positively associated with the severity of COVID-19 (including severe, critical, or fatal outcomes), but some of the confounding factors are not considered. The aim of this meta-analysis was to estimate the adjusted relationship between elevated procalcitonin on admission and the severity of COVID-19. Materials and Methods: We searched 1805 articles from PubMed, Web of Science, and Embase databases up to 2 April 2021. The articles were selected which reported the adjusted relationship applying multivariate analysis between PCT and the severity of COVID-19. The pooled effect estimate was calculated by the random-effects model. Results: The meta-analysis included 10 cohort studies with a total of 7716 patients. Patients with elevated procalcitonin on admission were at a higher risk of severe and critical COVID-19 (pooled effect estimate: 1.77, 95% confidence interval (CI): 1.38-2.29; I2 = 85.6%, p < 0.001). Similar results were also observed in dead patients (pooled effect estimate: 1.77, 95% CI: 1.36-2.30). After adjusting for diabetes, the positive association between PCT and the severity of COVID-19 decreased. Subgroup analysis revealed heterogeneity between studies and sensitivity analysis showed that the results were robust. There was no evidence of publication bias by Egger's test (p = 0.106). Conclusions: Higher procalcitonin is positively associated with the severity of COVID-19, which is a potential biomarker to evaluate the severity of COVID-19 and predict the prognosis.
| S-EPMC8227321 | biostudies-literature
Project description:BackgroundThe current 2019 novel coronavirus disease (COVID-19) pandemic is a major threat to global health. It is currently uncertain whether and how liver injury affects the severity of COVID-19. Therefore, we conducted a meta-analysis to determine the association between liver injury and the severity of COVID-19.MethodsA systematic search of the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2022, was performed to analyse the reported liver chemistry data for patients diagnosed with COVID-19. The pooled odds ratio (OR), weighted mean difference (WMD) and 95% confidence interval (95% CI) were assessed using a random-effects model. Furthermore, publication bias and sensitivity were analyzed.ResultsForty-six studies with 28,663 patients were included. The pooled WMDs of alanine aminotransferase (WMD = 12.87 U/L, 95% CI: 10.52-15.23, I 2 = 99.2%), aspartate aminotransferase (WMD = 13.98 U/L, 95% CI: 12.13-15.83, I 2 = 98.2%), gamma-glutamyl transpeptidase (WMD = 20.67 U/L, 95% CI: 14.24-27.10, I 2 = 98.8%), total bilirubin (WMD = 2.98 μmol/L, 95% CI: 1.98-3.99, I 2 = 99.4%), and prothrombin time (WMD = 0.84 s, 95% CI: 0.46-1.23, I 2 = 99.4%) were significantly higher and that of albumin was lower (WMD = -4.52 g/L, 95% CI: -6.28 to -2.75, I 2 = 99.9%) in severe cases. Moreover, the pooled OR of mortality was higher in patients with liver injury (OR = 2.72, 95% CI: 1.18-6.27, I 2 = 71.6%).ConclusionsHepatocellular injury, liver metabolic, and synthetic function abnormality were observed in severe COVID-19. From a clinical perspective, liver injury has potential as a prognostic biomarker for screening severely affected patients at early disease stages.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, Identifier: CRD42022325206.
| S-EPMC9932800 | biostudies-literature
Project description:This study aimed to evaluate the association of interleukin-6 (IL-6) level with the poor outcomes in coronavirus disease 2019 (COVID-19) patients by utilizing a meta-analysis based on adjusted effect estimates. We searched the keywords from PubMed, Web of Science, and EMBASE on August 14, 2020. The pooled effects and 95% confidence interval (95% CI) were estimated by Stata 11.2. Subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was implemented to assess the stability of the results. Begg's test and Egger's test were conducted to assess the publication bias. Sixteen articles with 8752 COVID-19 patients were finally included in the meta-analysis. The results based on random-effects model indicated that elevated value of IL-6 was significantly associated with adverse outcomes in patients with COVID-19 (pooled effect = 1.21, 95% CI 1.13-1.31, I2 = 90.7%). Subgroup analysis stratified by disease outcomes showed consistent results (severe: pooled effect = 1.18, 95% CI 1.05-1.31; ICU (intensive care unit) admission: pooled effect = 1.90, 95% CI 1.04-3.47; death: pooled effect = 3.57, 95% CI 2.10-6.07). Meta-regression indicated that study design was a source of heterogeneity. Publication bias was existent in our analysis (Begg's test: P = 0.007; Egger's test: P < 0.001). In conclusion, the elevated IL-6 level is an independent risk factor associated with adverse outcomes in patients with COVID-19.
| S-EPMC7567652 | biostudies-literature
Project description:With the rising demand for improved COVID-19 disease monitoring and prognostic markers, studies have aimed to identify biomarkers using a range of screening methods. However, the selection of biomarkers for validation from large datasets may result in potentially important biomarkers being overlooked when datasets are considered in isolation. Here, we have utilized a meta-summary approach to investigate COVID-19 biomarker datasets to identify conserved biomarkers of COVID-19 severity. This approach identified a panel of 17 proteins that showed a consistent direction of change across two or more datasets. Furthermore, bioinformatics analysis of these proteins highlighted a range of enriched biological processes that include inflammatory responses and compromised integrity of physiological systems including cardiovascular, neurological, and metabolic. A panel of upstream regulators of the COVID-19 severity biomarkers were identified, including chemical compounds currently under investigation for COVID-19 treatment. One of the upstream regulators, interleukin 6 (IL6), was identified as a "master regulator" of the severity biomarkers. COVID-19 disease severity is intensified due to the extreme viral immunological reaction that results in increased inflammatory biomarkers and cytokine storm. Since IL6 is the primary stimulator of cytokines, it could be used independently as a biomarker in determining COVID-19 disease progression, in addition to a potential therapeutic approach targeting IL6. The array of upstream regulators of the severity biomarkers identified here serve as attractive candidates for the development of new therapeutic approaches to treating COVID-19. In addition, the findings from this study highlight COVID-19 severity biomarkers which represent promising, robust biomarkers for future validation studies for their use in defining and monitoring disease severity and patient prognosis.
| S-EPMC9420723 | biostudies-literature
Project description:Genome-wide DNA methylation analysis of COVID-19 severity using the Illumina HumanMethylationEPIC microarray platform to analyze over 850,000 methylation sites, comparing COVID-19 patients with patients presenting with respiratory symptoms, but negative for COVID-19, using whole blood tissue.
2021-05-31 | GSE174818 | GEO
Project description:Using RNA-seq and high-resolution mass spectrometry we performed a comprehensive systems analysis on 128 plasma and leukocyte samples from hospitalized patients with or without COVID-19 (n=102 and 26 respectively) and with differing degrees of disease severity. We generated abundance measurements for over 17,000 transcripts, proteins, metabolites, and lipids and compiled them with clinical data into a curated relational database. This resource offers the unique opportunity to perform systems analysis and cross-ome correlations to both molecules and patient outcomes. In total 219 molecular features were mapped with high significance to COVID-19 status and severity, including those involved in processes such as complement system activation, dysregulated lipid transport, and B cell activation. In one example, we detected a trio of covarying molecules – citrate, plasmenyl-phosphatidylcholines, and gelsolin (GSN) – that offer both pathophysiological insight and potential novel therapeutic targets. Further, our data revealed in some cases, and supported in others, that several biological processes were dysregulated in COVID-19 patients including vessel damage, platelet activation and degranulation, blood coagulation, and acute phase response. For example, we observed that the coagulation-related protein, cellular fibronectin (cFN), was highly increased within COVID-19 patients and provide new evidence that the upregulated proteoform stems from endothelial cells, consistent with endothelial injury as a major activator of the coagulation cascade. The abundance of prothrombin, which is cleaved to form thrombin during clotting, was significantly reduced and correlated with severity and might help to explain the hyper coagulative environment of SARS-CoV-2 infection. From transcriptomic analysis of leukocytes, we concluded that COVID-19 patients with acute respiratory distress syndrome (ARDS) demonstrated a phenotype that overlapped with, but was distinct from, that found in patients with non-COVID-19-ARDS. To aid in the global efforts toward elucidation of disease pathophysiology and therapeutic development, we created a web-based tool with interactive visualizations allowing for easy navigation of this systems-level compendium of biomolecule abundance in relation to COVID-19 status and severity. Finally, we leveraged these multi-omic data to predict COVID-19 patient outcomes with machine learning, which highlighted the predictive power of these expansive molecular measurements beyond the standardized clinical estimate of 10-year survival Charlson score.
2020-08-29 | GSE157103 | GEO
Project description:Abstract Background Previous studies reported that patients with asthma showed higher levels of interleukin (IL)‐33 in peripheral blood, compared to healthy control (HCs). However, we also noticed that there were no significant differences of IL‐33 levels between controls and asthma patients in a recent study. We aim to conduct this meta‐analysis and evaluate the feasibility of IL‐33 in peripheral blood that may act as a promising biomarker in asthma. Methods Articles published before December 2022 were searched in these databases (PubMed, Web of Science, EMBASE, and Google Scholar). We used STATA 12.0 software to compute the results. Results The study showed that asthmatics showed higher IL‐33 level in serum and plasma, compared to HCs (serum: standard mean difference [SMD] 2.06, 95% confidence interval [CI] 1.12−3.00, I2 = 98.4%, p < .001; plasma: SMD 3.67, 95% CI 2.32−5.03, I2 = 86.0%, p < .001). Subgroup analysis indicated that asthma adults showed higher IL‐33 level in serum, compared to HCs, whereas no significant difference in IL‐33 level in serum was showed between asthma children and HCs (adults: SMD 2.17, 95% CI 1.09−3.25; children: SMD 1.81, 95% CI −0.11 to 3.74). The study indicated that moderate and severe asthmatics showed higher IL‐33 level in serum, compared to mild asthmatics (SMD 0.78, 95% CI 0.41−1.16, I2 = 66.2%, p = .011). Conclusions In conclusion, the main findings of present meta‐analysis suggested that there was a significant correlation between IL‐33 levels and the severity of asthma. Therefore, IL‐33 levels of either serum or plasma may be regarded as a useful biomarker of asthma or the degree of disease. In conclusion, the main findings of present meta‐analysis suggested that there was significant correlation between interleukin (IL)‐33 levels and the severity of asthma. Therefore, the IL‐33 levels of either serum or plasma may be regarded as a useful biomarker of asthma or the degree of disease. However, we can not ignore the influences of ethnic and age factors on the IL‐33 levels. It is encouraged that data from multi‐center, well‐designed and large sample size studies should be conducted for validating the clinical value of IL‐33 on asthma.
| S-EPMC10116908 | biostudies-literature
Project description:BackgroundMany studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19.MethodsWe searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods.ResultsWe included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37-2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09-3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74-2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%-10.9%) (after adjusting for heterogeneity).ConclusionsDiabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.
| S-EPMC7200339 | biostudies-literature
Project description:BackgroundThe association between metabolic-associated fatty liver disease (MAFLD) and disease progression in patients with the coronavirus disease 2019 (COVID-19) are unclear.AimsTo explore the association between MAFLD and the severity of COVID-19 by meta-analysis.MethodsWe conducted a literature search using PubMed, EMBASE, Medline (OVID), and MedRxiv from inception to July 6, 2020. Newcastle-Ottawa Scale (NOS) and Stata 14.0 were used for quality assessment of included studies as well as for performing a pooled analysis.ResultsA total of 6 studies with 1,293 participants were included after screening. Four studies reported the prevalence of MAFLD patients with COVID-19, with a pooled prevalence of 0.31 for MAFLD (95CI 0.28, 0.35, I2 = 38.8%, P = 0.179). MAFLD increased the risk of COVID-19 disease severity, with a pooled OR of 2.93 (95CI 1.87, 4.60, I2 = 34.3%, P = 0.166).ConclusionIn this meta-analysis, we found that a high percentage of patients with COVID-19 had MAFLD. Meanwhile, MAFLD increased the risk of disease progression among patients with COVID-19. Thus, better intensive care and monitoring are needed for MAFLD patients infected by SARS-COV-2.
| S-EPMC7498251 | biostudies-literature
Project description:BackgroundIn this systematic review and meta-analysis, we aimed to investigate the correlation of D-dimer levels measured on admission with disease severity and the risk of death in patients with coronavirus disease 2019 (COVID-19) pneumonia.Materials and methodsWe performed a comprehensive literature search from several databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale (NOS). D-dimer levels were pooled and compared between severe/non-severe and surviving/non-surviving patient groups. Weighted mean difference (WMD), risk ratios (RRs) and 95% confidence intervals (CIs) were analyzed.ResultsThirty-nine studies reported on D-dimer levels in 5750 non-severe and 2063 severe patients and 16 studies reported on D-dimer levels in 2783 surviving and 697 non-surviving cases. D-dimer levels were significantly higher in patients with severe clinical status (WMD: 0.45 mg/L, 95% CI: 0.34-0.56; p < 0.0001). Non-surviving patients had significantly higher D-dimer levels compared to surviving patients (WMD: 5.32 mg/L, 95% CI: 3.90-6.73; p < 0.0001). D-dimer levels above the upper limit of normal (ULN) was associated with higher risk of severity (RR: 1.58, 95% CI: 1.25-2.00; p < 0.0001) and mortality (RR: 1.82, 95% CI: 1.40-2.37; p < 0.0001).ConclusionIncreased levels of D-dimer levels measured on admission are significantly correlated with the severity of COVID-19 pneumonia and may predict mortality in hospitalized patients.
| S-EPMC7489326 | biostudies-literature