Prognostic roles of KL-6 in disease severity and lung injury in COVID-19 patients: A longitudinal retrospective analysis

Abstract

To investigate the dynamic changes of Krebs von den Lungen-6 (KL-6) among patients with coronavirus disease 2019 (COVID-19) and the role of KL-6 as a noninvasive biomarker for predicting long-term lung injury, the clinical information and laboratory tests of 166 COVID-19 patients were collected, and a correlation analysis between KL-6 and other parameters was conducted. There were 17 (10.2%, 17/166) severe/critical and 149 (89.8%, 149/166) mild COVID-19 patients in our cohort. Serum KL-6 was significantly higher in severe/critical COVID-19 patients than in mild patients (median 898.0 vs. 451.2 U/ml, p < .001). KL-6 was next confirmed to be a sensitive and specific biomarker for distinguishing mild and severe/critical patients and correlate to computed tomography lung lesions areas. Serum KL-6 concentration during the follow-up period (>100 days postonset) was well correlated to those concentrations within 10 days postonset (Pearson r = .867, p < .001), indicating the prognostic value of KL-6 levels in predicting lung injury after discharge. Finally, elevated KL-6 was found to be significantly correlated to coagulation disorders, and T cells subsets dysfunctions. In summary, serum KL-6 is a biomarker for assessing COVID-19 severity and predicting the prognosis of lung injury of discharged patients.

Keywords: COVID-19; KL-6; lung injury; prognosis.

Figure 1

Serum Krebs von den Lungen‐6 (KL‐6) levels of healthy control (n = 59), mild (n = 149), and severe/critical coronavirus disease 2019 patients (n = 17). ***p < .001

Figure 2

Linear regression models predict Krebs von den Lungen‐6 (KL‐6) at >100 days postonset among all coronavirus disease 2019 (COVID‐19) cases (left panel, n = 81) and COVID‐19 cases with KL‐6 ≥300 U/ml during hospitalization (right panel, n = 60)

Figure 3

Linear correlations between computed tomography (CT) lung lesions areas and the Krebs von den Lungen‐6 (KL‐6) values within the previous week (A) (n = 73) and within the next week (B) (n = 80)

Figure 4

Dynamic profile of the coagulation indexes of a severe/critical patient. LDH is also shown as a biomarker for COVID‐19 severity. A dotted line in red or green represents the upper or lower normal limit of each index (right Y‐axis), respectively. APTT, activated partial thromboplastin time; COVID‐19, coronavirus disease 2019; FDP, fibrin degradation product; Fib, fibrinogen; INR, international normalized ratio; KL‐6, Krebs von den Lungen‐6; LDH, lactate dehydrogenase; PT, prothrombin time; PTA, prothrombin time activity; TT, thrombin time