Exploratory analysis of serum Krebs von den Lungen-6, blood gas analysis & Brixia score in determining COVID-19 severity & mortality

Abstract

Background & objectives Krebs von den Lungen-6 (KL-6) is primarily expressed by the damaged type II pneumocytes. In this context, the relationship of KL-6 with blood gas analysis (BGA) parameters and Brixia score is still limitedly discussed. This study aims to analyze the correlation of KL-6, BGA and Brixia scores to the severity and mortality of COVID-19. Methods A cross-sectional study was conducted in adult COVID-19 positive individuals at Universitas Airlangga Hospital, Surabaya, East Java, Indonesia, from March to August 2021. KL-6, BGA, and Brixia scores were compared according to severity (severe vs. non-severe) and mortality (non-survivor vs. survivor). The receiver operating characteristic (ROC) analysis was also performed to define the optimal cut-off, sensitivity, as well as the specificity of KL-6, BGA and Brixia scores to determine the COVID-19 severity and mortality. Results Total 35 severe and 20 non-severe COVID-19 positive individuals were enrolled in this study. Of those, there were 22 non-survivors. No significant difference in serum KL-6 levels was observed in the severity and mortality groups. KL-6 and HCO3- had positive correlation in the severe group (r=0.37). KL-6 and Brixia scores showed a significant negative correlation among COVID-19 positive individuals (r=-0.283; P=0.036). KL-6 and Brixia scores together served as the best severity markers in the current study [AUC 0.809 (0.697-0.920); Sn/Sp=0.686/0.900)], followed by KL-6 and P/F ratio [AUC 0.800 (0.637-0.963); Sn/Sp=0.971/0.750]. Interpretation & conclusions The findings of this study suggest that KL-6 has the potential to be a useful adjunct laboratory parameter to the BGA and Brixia score representing COVID-19 severity and mortality.

Keywords: Biomarker; COVID-19; KL-6; SARS-CoV-2-severity; blood gas analysis; brixia; mortality.

Fig. 1.

Correlation strengths between KL-6 and several COVID-19 severity parameters of BGA and CXR. (A) pH, (B) pCO₂, (C) BE, (D) HCO₃^–, (E) P/F ratio and (F) Brixia score. BE, base excess; BGA, blood gas analysis; COVID-19, Coronavirus disease 2019; CXR, chest X-ray; KL-6, Krebs von den Lungen-6; P/F ratio, PaO₂/FiO₂ ratio; pCO₂, partial carbon dioxide pressure.

Fig. 2.

Correlation strengths between KL-6 and several COVID-19 mortality parameters of BGA and CXR. (A) pH, (B) pCO₂, (C) BE, (D) HCO₃^–, (E) P/F ratio and (F) Brixia score.

Fig. 3.

ROC curve of KL-6, P/F ratio, Brixia score and their combinations in COVID-19 severity (A, B) and mortality (C, D). ROC, receiver operating characteristic.