Peak value of serum KL-6 may be useful for predicting poor prognosis of severe COVID-19 patients

Abstract

Background: Serum Krebs von den Lungen 6 (KL-6), which reflects alveolar epithelial injury, was reported to be useful to predict the progression of pneumonitis induced by COVID-19 in the early phase. This study aimed to evaluate the peak value of serum KL-6 during hospitalization for COVID-19 to discover a more useful biomarker for predicting prognosis in COVID-19 patients.

Methods: In this retrospective, single-center, observational study, we analyzed the data of 147 hospitalized patients who required supplemental oxygen, high-flow oxygen therapy, or invasive mechanical ventilation for respiratory failure due to COVID-19 from March 2020 to February 2021. We extracted data on patient sex, age, comorbidities, treatment, and biomarkers including the initial and peak values of KL-6. Inclusion criteria were examination of the studied biomarkers at least once within 3 days of admission, then at least once a week, and at a minimum, at least twice during the entire hospitalization. Area under the receiver operating curve (AUC) was analyzed to determine the accuracy of several biomarkers including KL-6 and LDH for predicting poor prognosis defined as survivors requiring invasive mechanical ventilation for over 28 days or non-survivors of COVID-19. Univariable and multivariate logistic regression analyses were performed to investigate the prognostic value of the baseline characteristics and biomarkers.

Results: Among the 147 patients, 108 (73.5%) had a good prognosis and 39 (26.5%) had a poor prognosis. The AUC analysis indicated that peak KL-6 showed precise accuracy in the discrimination of patients with poor prognosis (AUC 0.89, p < 0.001). The best cut-off value for KL-6 concentration was 966 U/mL (sensitivity 81.6%, specificity84.3%). After adjustment, increasing peak values of KL-6 or LDH were associated with a high risk of poor prognosis, with an adjusted odds ratio of 1.35 for peak value of KL-6, per 100 U/mL increase (95% CI 1.17-1.57, p < 0.001) and 2.16 for peak value of LDH, per 100 U/L increase (95% CI 1.46-3.20, p < 0.001).

Conclusions: Peak values of KL-6 and LDH measured during hospitalization might help to identify COVID-19 patients with respiratory failure who are at higher risk for a poor prognosis.

Keywords: Biomarker; COVID-19; KL-6; Prognosis.