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 | 2021 Jan
REPOSITORIES: biostudies-literature
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Elevated interleukin-6 is associated with severity of COVID-19: A meta-analysis.
Zhu Jieyun J Pang Jielong J Ji Pan P Zhong Zhimei Z Li Hongyuan H Li Bocheng B Zhang Jianfeng J
Journal of medical virology 20201030 1
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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:BackgroundDivergence between deterioration to life-threatening COVID-19 or clinical improvement occurs for most within the first 14 days of symptoms. Life-threatening COVID-19 shares clinical similarities with Macrophage Activation Syndrome, which can be driven by elevated Free Interleukin-18 (IL-18) due to failure of negative-feedback release of IL-18 binding protein (IL-18bp). We, therefore, designed a prospective, longitudinal cohort study to examine IL-18 negative-feedback control in relation to COVID-19 severity and mortality from symptom day 15 onwards.Methods662 blood samples, matched to time from symptom onset, from 206 COVID-19 patients were analysed by enzyme-linked immunosorbent assay for IL-18 and IL-18bp, enabling calculation of free IL-18 (fIL-18) using the updated dissociation constant (Kd) of 0.05 nmol. Adjusted multivariate regression analysis was used to assess the relationship between highest fIL-18 and outcome measures of COVID-19 severity and mortality. Re-calculated fIL-18 values from a previously studied healthy cohort are also presented.ResultsRange of fIL-18 in COVID-19 cohort was 10.05-1157.7 pg/ml. Up to symptom day 14, mean fIL-18 levels increased in all patients. Levels in survivors declined thereafter, but remained elevated in non-survivors. Adjusted regression analysis from symptom day 15 onwards showed a 100 mmHg decrease in PaO2/FiO2 (primary outcome) for each 37.7 pg/ml increase in highest fIL-18 (p < 0.03). Per 50 pg/ml increase in highest fIL-18, adjusted logistic regression gave an odds-ratio (OR) for crude 60-day mortality of 1.41 (1.1-2.0) (p < 0.03), and an OR for death with hypoxaemic respiratory failure of 1.90 [1.3-3.1] (p < 0.01). Highest fIL-18 was associated also with organ failure in patients with hypoxaemic respiratory failure, with an increase of 63.67 pg/ml for every additional organ supported (p < 0.01).ConclusionsElevated free IL-18 levels from symptom day 15 onwards are associated with COVID-19 severity and mortality. ISRCTN: #13450549; registration date: 30/12/2020.
| S-EPMC9949911 | 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:BackgroundPrevious 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.MethodsArticles 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.ResultsThe 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).ConclusionsIn 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.
| S-EPMC10116908 | biostudies-literature
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: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: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:Telomere shortening, a marker of cellular aging, has been linked to hospitalization and the severity of COVID-19. In this systematic review and meta-analysis, the mean difference in telomere length between non-severe and severe COVID-19 individuals was pooled to determine the association between short telomeres and COVID-19 severity. Relevant studies were retrieved through searches conducted in PubMed-Medline, Scopus, EMBASE, Medrxiv, Biorxiv, EuroPMC, and SSRN databases up to November 2022. Selected studies were systematically reviewed and assessed for risk of bias using AXIS tool. The standardized mean difference in telomere length between non-severe and severe COVID-19 was pooled using random-effects model. A total of thirteen studies were included in the review, out of which seven (1332 patients with the severe COVID-19 disease and 6321 patients with non-severe COVID-19) were eligible for meta-analysis. The estimated pooled mean difference in Leukocyte telomere length between severe COVID-19 and non-severe COVID-19 was 0.39 (95% CI - 0.02 to 0.81, I2 = 93.5%) with substantial heterogeneity. Our findings do not provide clear evidence for association of shorter telomere length and severe COVID-19 disease. More extensive studies measuring absolute telomere length with age and gender adjustments are needed to draw definitive conclusions on the potential causal association between telomere shortening and COVID-19 severity.
| S-EPMC10234232 | 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