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.

Serum KL-6 and the mortality of patients with connective tissue disease-associated interstitial lung disease: A meta-analysis

“…Elevated serum levels of KL-6 have been identified as a biomarker for alveolar epithelial proliferation and injury in various respiratory conditions (10), including acute respiratory distress syndrome (11), hypersensitivity pneumonia (12), idiopathic interstitial pneumonia (13), pulmonary sarcoidosis (14), coronavirus disease 2019 (COVID-19) (15), and CTD-ILD (16). Furthermore, several studies have indicated the potential predictive value of serum KL-6 in determining the prognosis of individuals with severe lung conditions, including idiopathic pulmonary fibrosis (17) and COVID-19 (18). Nevertheless, research examining the correlation between serum KL-6 levels and mortality risk in patients with CTD-ILD has yielded conflicting results (19).…”