Dataset Information

Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19: A Systematic Review, Meta-Analysis, and Trial Sequence Analysis.

ABSTRACT:

Objective

This systematic review and meta-analysis aimed to find the association between serum Krebs von den Lungen-6 (KL-6) and the severity of Coronavirus disease 2019 (COVID-19) infection.

Data sources

Databases of Embase, PubMed, Web of Science, Science Direct, and Google Scholar were searched for studies reporting KL-6 levels in COVID-19 patients, published between January 2020 and September 30 2022.

Data synthesis

For comparison between the groups, standard mean difference (SMD) and 95% confidence intervals (CI) were computed as the effect sizes. Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were measured to assess the diagnostic power of KL-6. In addition, the summary receiver operating characteristics curve (sROC) was constructed to summarize the true positive (TP), and false positive (FP) rates. To validate the findings of meta-analysis, Trial Sequential Analysis (TSA) was conducted.

Results

Altogether 497 severe COVID-19 patients and 934 non-severe (mild to moderate) COVID-19 patients were included. Pooling of 12 studies indicated that the serum KL-6 level had significant association with severity of COVID-19 infection: standard mean difference = 1.18 (95% CI: 0.93-1.43), p = 0.01; I²: 58.56%]. Pooled diagnostic parameters calculated from eight studies were: sensitivity 0.53 (95% CI: 0.47-0.59); specificity 0.90 (95% CI: 0.88-0.93); positive likelihood ratio 4.80 (95% CI: 3.53-6.53); negative likelihood ratio 0.46 (95% CI: 0.32-0.68); and area under curve: 0.8841. Additionally, TSA verified the adequacy of sample size and robustness of the meta-analysis.

Conclusion

Serum KL-6 level has a moderate degree of correlation with the severity of COVID-19 infection but has low sensitivity. So, it is not recommended as a screening test for severe COVID-19 infection.

SUBMITTER: Shrestha AB

PROVIDER: S-EPMC9875321 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19: A Systematic Review, Meta-Analysis, and Trial Sequence Analysis.

Shrestha Abhigan Babu AB Pokharel Pashupati P Singh Harendra H Shrestha Sajina S Fioni

Clinical medicine insights. Circulatory, respiratory and pulmonary medicine 20230122

<h4>Objective</h4>This systematic review and meta-analysis aimed to find the association between serum Krebs von den Lungen-6 (KL-6) and the severity of Coronavirus disease 2019 (COVID-19) infection.<h4>Data sources</h4>Databases of Embase, PubMed, Web of Science, Science Direct, and Google Scholar were searched for studies reporting KL-6 levels in COVID-19 patients, published between January 2020 and September 30 2022.<h4>Data synthesis</h4>For comparison between the groups, standard mean diffe ...[more]

PMID: 36710717

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Project description:AimHypersensitivity pneumonitis (HP), also referred to as exogenous allergic alveolitis, is one of the most common interstitial lung diseases (ILDs). A potential immune biomarker, Krebs von den lgen-6 (KL-6) characterizes the progression and severity of HP. The meta-analysis in this study was conducted to elucidate the variations in the concentrations of KL-6 in different types of HP.MethodsA systematic search of various databases such as EMBASE, Pubmed, CNKI, VIP, Web of Science, and WanFang was carried out to find relevant published articles between January 1980 and August 2022 that explored the relationship between KL-6 and allergic pneumonia. Standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect sizes for comparison among different groups. The GSE47460 and GSE150910 datasets were downloaded to extract and validate the differences in KL-6 mRNA expression between HP lung tissue and healthy controls. Furthermore, the single-cell sequencing dataset GSE135893 was downloaded to extract KL-6 mRNA expression in type II alveolar epithelial cells to validate the differences between HP and healthy controls. Two researchers evaluated the quality of the included studies by employing Newcastle-Ottawa Scale. All the qualified studies were subjected to statistical analyses carried out utilizing RevMan 5.2, Stata 11.0, and R software 4.1.3.ResultsTwenty studies aligned perfectly with the inclusion criteria of the meta. The concentrations of KL-6 were substantially higher in the blood of HP patients as compared to the control group. Subgroup analyses were carried out in accordance with the allergen source and the results revealed that patients with different allergens had higher blood KL-6 concentrations than healthy controls. Additionally, different subgroups of subjects were created for meta-analysis as per the fibrosis status, race, measurement method, and sample type. The concentration of KL-6 in blood was much higher in all HP subgroups than in healthy control groups. Moreover, the bioinformatics analysis revealed that KL-6 mRNA expression was higher in HP lung tissue and type II alveolar epithelial cells as compared to healthy controls.ConclusionThe present meta-analysis and bioinformatics analysis suggested that the concentration levels of KL-6 varied between HP patients and healthy individuals, and the KL-6 concentrations may be higher in the blood samples of HP patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, CRD42022355334.

Project description:PurposeThe aim of the study was to estimate and compare the diagnostic accuracy of serum Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) for identifying interstitial lung disease (ILD) from non-ILD among connective tissue disease (CTD) patients.Materials and methodsOriginal articles on the diagnostic accuracy of serum KL-6 and SP-D in differentiating CTD-ILD from CTD-nonILD were identified from three public databases. The overall quality of evidence and methodologic quality of each eligible study were assessed by the Grading of Recommendations, Assessment, Development and Evaluation approach and Quality Assessment of Diagnostic Accuracy Studies, respectively. We used the bivariate model to calculate random-effect sensitivity, specificity, likelihood ratios, and area under curve. Furthermore, trial sequential analysis (TSA) was used to determine whether sample sizes incorporated in the meta-analysis were powerful for evaluating the diagnostic utility. Bayesian network analysis was performed to compare the diagnostic accuracy of 2 serum biomarkers in differentiating ILD among CTD patients and various subgroups.ResultsTwenty-nine studies were included in the quantitative synthesis. No threshold effects were observed (all P values >.05). For diagnosis of ILD among CTD patients, overall sensitivity and specificity of serum KL-6 were 0.76 (95% confidence interval [CI]: 0.68-0.82) and 0.89 (95% CI: 0.83-0.93), whereas those for serum SP-D were 0.65 (95% CI: 0.45-0.80) and 0.88 (95% CI: 0.80-0.93). Comprehensive comparison of 2 circulating biomarkers using back-calculated likelihood ratio (LR) demonstrated that serum KL-6 corresponded to a higher LR+ and a lower LR- in comparison to serum SP-D, as well as in SSc-ILD. TSA indicated that evidence for serum KL-6 and SP-D in identifying CTD-ILD is powerful; nonetheless, more trials were needed for validation of serum KL-6 and SP-D in differentiating CTD-ILD subtypes, including different CTD and ethnicities.ConclusionsThis meta-analysis suggested that serum KL-6 had superior diagnostic accuracy to SP-D for differentiating ILD from non-ILD among CTD patients, providing a convenient and non-invasive approach for screening and management of ILD among CTD patients.

Project description:There is a need for biomarkers to predict outcomes, including mortality, in interstitial lung disease (ILD). Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) are associated with lung damage and fibrosis in all ILDs and are related to important clinical outcomes. Though these two biomarkers have been associated with ILD outcomes, there are no studies that have evaluated their predictive potential in combination. This study aims to determine whether KL-6 and SP-D are linked to poor disease outcomes and mortality. Additionally, we plan to examine whether changes in KL-6 and SP-D concentrations correspond with changes in lung function and whether serial measurements improve their predictive potential to identify disease progression and mortality. Forty-four patients with ILD participated in a prospective 6-month longitudinal observational study. ILD patients who succumbed had the highest KL-6 levels (3990.4 U/mL (3490.0-4467.6)) and highest SP-D levels (256.1 ng/mL (217.9-260.0)), followed by those who deteriorated: KL-6 levels 1357.0 U/mL (822.6-1543.4) and SP-D levels 191.2 ng/mL (152.8-210.5). The generalized linear model (GLM) analysis demonstrated that changes in forced vital capacity (FVC), diffusing capacity of lungs for carbon monoxide (DLCO), forced expiratory volume in 1 s (FEV1), and partial pressure of arterial oxygen (PaO2) were correlated to changes in KL6 (p = 0.016, 0.014, 0.027, 0.047) and SP-D (p = 0.008, 0.012, 0.046, 0.020), respectively. KL-6 (odds ratio (OR): 2.87 (1.06-7.79)) and SPD (OR: 1.76 (1.05-2.97)) were independent predictors of disease progression, and KL-6 (hazard ratio (HR): 3.70 (1.46-9.41)) and SPD (HR: 2.58 (1.01-6.59)) were independent predictors of death by Cox regression analysis. Combined biomarkers (KL6 + SPD + CT + FVC) had the strongest ability to predict disease progression (AUC: 0.797) and death (AUC: 0.961), on ROC analysis. Elevated KL-6 and SPD levels are vital biomarkers for predicting the severity, progression, and outcomes of ILD. High baseline levels or an increase in levels over a six-month follow-up despite treatment indicate a poor prognosis. Combining KL6 and SPD with conventional measures yields a more potent prognostic indicator. Clinical studies are needed to test additional interventions, and future research will determine if this combined biomarker benefits different ethnicities globally.

Dataset Information

Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19: A Systematic Review, Meta-Analysis, and Trial Sequence Analysis.

Objective

Data sources

Data synthesis

Results

Conclusion

Publications

Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19: A Systematic Review, Meta-Analysis, and Trial Sequence Analysis.

Similar Datasets

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