Establishment Of Normal Reference Interval Of Serum KL-6 In Healthy Adults In Liaoning Province And Its Application Value In COVID-19 Infection

Objective:Serum KL-6 is an effective serological indicator for monitoring the progression and prognosis of interstitial lung disease.However,the reference interval currently used does not consider the interference of related influencing factors,and only the reference interval shared by adults is developed.In this study,Chinese healthy adults were selected as the research object to explore the influencing factors of serum KL-6 levels and establish the reference interval of serum KL-6 in Chinese healthy adults.And to investigate its application value in elderly patients with COVID-19 infection.Methods: The study included a healthy group and a COVID-19 group.The experimental subjects were physical examination subjects and elderly patients with moderate and severe novel coronavirus infection in Shengjing Hospital Affiliated to China Medical University from January 2021 to February 2023.There were 1254 patients in the healthy group,including 484 male patients and 770 female patients,with ≥120 patients of all ages.There were 187 elderly patients infected with the novel coronavirus,50 moderate cases and 137 severe cases.Beckman Coulter’s AU5800 series automatic biochemical analyzer was used to detect KL-6,and KL-6 latex immunoturbidimetry kit produced by Jiangsu Baoban Biotechnology Co.,LTD was used to detect KL-6.Kolmogorov-Smirnov test was used to analyze the normality of quantitative data;multivariate analysis of variance was used for the comparison of normal distribution data between groups;LSD test was used for the comparison between groups;normal approximation method was used to establish reference interval;Kruskal-Wallis H test was used for the comparison between groups of biased distribution data.Comparison between groups was conducted by Mann-Whitney U rank sum test,and reference interval was established by percentile method.Verify the established reference interval.The established reference interval was verified.Receiver operating characteristic curve(ROC)was used to determine the cut-off value.Spearman correlation analysis was used for correlation analysis.Linear regression analysis was used to analyze the relevant indicators.Results:1.(1)Comparison of serum KL-6 levels in different gender and age subgroups:The serum KL-6 level of young men 211.60(171.60-257.00)U/m L was significantly higher than that of young women 158.60(135.70-195.40)U/m L.There was no significant difference in the serum KL-6 level between men and women in the middle-aged subgroup and the elderly subgroup.(2)With the increase of age,the serum KL-6 level gradually increased: male young subgroup 211.60(171.60-257.00)U/m L vs.Middle-aged men 234.05(194.08-303.20)U/m L vs.259.00(214.15-319.15)U/m L in elderly male subgroup,158.60(135.70-195.40)U/m L in young female subgroup vs.Middle-aged female subgroup 230.00(183.80-286.50)U/m L vs.Female elderly subgroup 243.10(201.45-325.78)U/m L.(3)Establishment of normal reference intervals:The normal reference intervals were(100.8-435.3)U/m L for male young subgroup,(81.8-312.7)U/m L for female young subgroup,(131.3-457.9)U/m L for middle-aged subgroup,and(154.1-527.1)U/m L for elderly subgroup.2.(1)The serum KL-6 level of the COVID-19 group 530.90(356.30-902.90)U/m L was significantly higher than that of the elderly subgroup 250.10(205.30-322.30)U/m L,P<0.05(2)The serum KL-6 level of322.8U/m L with the maximum Youden index was selected as the cut-off value for the diagnosis of 2019-ncov infection in elderly patients.The corresponding Area Under ROC Curve(AUC)was 0.868,the sensitivity was 84%,and the specificity was 76%.3.(1)The serum KL-6 level in the severe COVID-19 subgroup was 659.8(388.6-1009.1)U/m L,which was significantly higher than that in the moderate subgroup 383.1(265.1-497.1)U/m L,P<0.05.(2)The serum KL-6 level of 527.1U/m L with the highest Youden index was selected as the cut-off value for the differential diagnosis of moderate and severe COVID-19 infection in elderly patients,and the corresponding AUC was 0.762,the sensitivity was 64%,and the specificity was 84%.(3)In elderly patients with moderate and severe COVID-19 infection,serum KL-6 levels were negatively correlated with finger oxygen saturation,positively correlated with C-reactive protein(CRP)levels,and positively correlated with arterial partial pressure of oxygen(PAO2).Pa O2)/fraction of inspired oxygen(Fi O2)and Interleukin-6(IL-6)levels were not significantly correlated.Conclusion: In this study,the serum KL-6 reference interval of healthy adults in Liaoning area was established.The cut-off value of serum KL-6 in elderly patients with COVID-19 was established.The cut-off value of serum KL-6 in aged patients with moderate and severe COVID-19 infection was established.It was found that in patients with COVID-19,serum KL-6 level was negatively correlated with finger oxygen saturation,positively correlated with CRP level,and had no significant correlation with Pa O2/Fi O2 and IL-6 level.This study improved the deficiency of serum KL-6 reference interval and novel coronavirus infection,and laid a solid foundation for subsequent research.