An in-depth investigation of serum Krebs von den Lungen-6 and other biomarkers in COVID-19 severity and mortality

Abstract

Krebs von den Lungen-6 (KL-6) is a glycoprotein mainly expressed by type II pneumocytes and recently known as a lung injury biomarker. However, the number of studies is still limited, especially in Indonesian COVID-19 populations. Therefore, we aim to provide correlation, sensitivity, and specificity analyses of KL-6 and other biomarkers in Indonesian COVID-19 severity and mortality. We conducted a cross-sectional study involving adult COVID-19 patients at Universitas Airlangga Hospital, Surabaya, East Java, Indonesia, between March 26, 2021, and August 25, 2021. KL-6 and other biomarker levels were compared according to severity (severe versus non-severe) and mortality (non-survivor versus survivor). We also included the receiver operating characteristic analysis to define the optimal cut-off, sensitivity, and specificity of KL-6 to determine COVID-19 severity and mortality. We enrolled 78 COVID- 19 patients (23 non-survivors), including 39 non-severe and 39 severe patients. There was no significant difference in serum KL-6 levels, neither in severity nor mortality groups. KL-6 had the strongest positive correlations with ferritin in severe patients (r=0.313) and non-survivors (r=0.467). We observed that the best sensitivity was KL-6 combined with platelet-to- lymphocyte ratio (PLR) (0.818) in severe patients and with neutrophil-to-lymphocyte ratio (NLR)/PLR/ferritin/C-reactive protein (0.867) in non-survivors. In contrast, the best specificity was found when KL-6 was combined with NLR/D-dimer (0.750) in severe patients and with D-dimer (0.889) in non-survivors. Serum KL-6 is a useful auxiliary laboratory evaluation index for COVID-19 lung injury to depict its severity and mortality.