KL-6 as a predictor of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) and mortality in critically ill COVID-19 patients: A single-center retrospective cohort study

Abstract

This study evaluated the predictive value of Krebs von den Lungen-6 (KL-6) for the development of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) and its association with mortality in critically ill COVID-19 patients. A retrospective single-center cohort study was conducted on critically ill COVID-19 patients who required high-flow oxygen or mechanical ventilation between January 2021 and June 2023. Serial serum KL-6 levels were measured at admission and weekly thereafter. The predictive performance of initial KL-6 was assessed using ROC curve analysis, and risk factors for CAPA and 30-day mortality were analyzed using multivariable models. Among 238 patients, 25 (10.5%) developed CAPA. Initial KL-6 demonstrated good discriminative ability for CAPA prediction (AUC 0.745; 95% CI: 0.685-0.799), with an optimal cutoff of 270.9 U/ml (sensitivity: 88.0%, specificity: 55.4%). KL-6 ≥ 270.9 U/ml remained independently associated with CAPA (aHR: 9.66; 95% CI: 2.28-40.89) after multivariable analysis. Serial measurements showed a trend toward a greater increase in KL-6 levels among CAPA patients than non-CAPA patients (median difference: 259.9 vs. 73.0 U/ml, P = .053). Additional independent predictors of CAPA included inotropic/vasopressor support, diabetes mellitus, and tocilizumab use. CAPA patients had higher all-cause 30-day mortality (60.8% vs. 45.2%; P = .020), which remained significant after adjustment (aHR: 2.19; 95% CI: 1.08-4.15). Furthermore, KL-6 was independently associated with 30-day mortality (aHR: 1.03 per 100 U/ml; 95% CI: 1.00-1.07). These findings suggest that KL-6 is a promising biomarker for predicting CAPA and mortality in critically ill COVID-19 patients.

Keywords: COVID-19; KL6 antigen; SARS-CoV-2; aspergillosis; human; mortality.