Increased KL-6 levels in moderate to severe COVID-19 infection

Abstract

Background The global coronavirus disease 2019 (COVID-19) has presented significant challenges and created concerns worldwide. Besides, patients who have experienced a SARS-CoV-2 infection could present post-viral complications that can ultimately lead to pulmonary fibrosis. Serum levels of Krebs von den Lungen 6 (KL-6), high molecular weight human MUC1 mucin, are increased in the most patients with various interstitial lung damage. Since its production is raised during epithelial damages, KL-6 could be a helpful non-invasive marker to monitor COVID-19 infection and predict post-infection sequelae. Methods We retrospectively evaluated KL-6 levels of 222 COVID-19 infected patients and 70 healthy control. Serum KL-6, fibrinogen, lactate dehydrogenase (LDH), platelet-lymphocytes ratio (PLR) levels and other biological parameters were analyzed. This retrospective study also characterized the relationships between serum KL-6 levels and pulmonary function variables. Results Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects (470 U/ml vs 254 U/ml, P <0.00001). ROC curve analysis enabled us to identify that KL-6 > 453.5 U/ml was associated with COVID-19 (AUC = 0.8415, P < 0.0001). KL-6 level was positively correlated with other indicators of disease severity such as fibrinogen level (r = 0.1475, P = 0.0287), LDH level (r = 0,31, P = 0,004) and PLR level (r = 0.23, P = 0.0005). However, KL-6 levels were not correlated with pulmonary function tests (r = 0.04, P = 0.69). Conclusions KL-6 expression was correlated with several disease severity indicators. However, the association between mortality and long-term follow-up outcomes needs further investigation. More extensive trials are required to prove that KL-6 could be a marker of disease severity in COVID-19 infection.

Unraveling the enigma: The emerging significance of pulmonary surfactant proteins in predicting, diagnosing, and managing COVID‐19

“…It has been observed to be higher than normal in individuals with COVID-19, especially in those with moderate to severe symptoms. Compared to the increase in the lung-specific biomarker KL-6, 76 the increase in SP-A and SP-D initiated at an earlier stage in pneumonia. 36 The scores derived from the analysis of chest CT scans exhibited a noteworthy and positive association with the levels of serum SP-A and SP-D. 77 As pneumonia advanced from a nonsevere state to a severe one, there was a substantial rise in the levels of serum SP-A and SP-D, which was closely accompanied by clinical observations and CT scans.…”

“…It has been observed to be higher than normal in individuals with COVID‐19, especially in those with moderate to severe symptoms. Compared to the increase in the lung‐specific biomarker KL‐6, 76 the increase in SP‐A and SP‐D initiated at an earlier stage in pneumonia 36 . The scores derived from the analysis of chest CT scans exhibited a noteworthy and positive association with the levels of serum SP‐A and SP‐D 77 .…”

Association of Serum Krebs von den Lungen-6 (KL-6) Levels and Disease Severity in Patients Hospitalized with COVID-19

“…Based on these observations, KL-6 was proposed as a helpful marker of disease activity. Furthermore, few studies on COVID-19 have assessed KL-6 as a measure of disease severity and prognosis, but their findings are inconsistent (15)(16)(17)(18). When compared to the healthy control group, Cambier et al found enhanced KL-6 serum levels in SARS-CoV-2 infected individuals; however, KL-6 levels did not correlate with the oxygen saturation of the patients or their admission to an intensive care unit (ICU) (15).…”

“…Furthermore, few studies on COVID-19 have assessed KL-6 as a measure of disease severity and prognosis, but their findings are inconsistent (15)(16)(17)(18). When compared to the healthy control group, Cambier et al found enhanced KL-6 serum levels in SARS-CoV-2 infected individuals; however, KL-6 levels did not correlate with the oxygen saturation of the patients or their admission to an intensive care unit (ICU) (15). Fifty-seven severe and 18 non-severe patients were included in a study conducted by Suryananda et al On the first and sixth days of the illness, there was no change in the blood KL-6 levels between the two groups (16).…”