{"title":"肺损伤及纤维化标志物KL-6、TGF-β1、FGF-2在COVID-19患者中的预后价值","authors":"Hazan Karadeniz, Aslıhan Avanoğlu Güler, Hasan Selçuk Özger, Pınar Aysert Yıldız, Gonca Erbaş, Gülendam Bozdayı, Tuba Deveci Bulut, Özlem Gülbahar, Dilek Yapar, Hamit Küçük, Mehmet Akif Öztürk, Abdurrahman Tufan","doi":"10.1177/11772719221135443","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-β1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19.</p><p><strong>Methods: </strong>Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-β1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed.</p><p><strong>Results: </strong>Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, <i>P</i> = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis.</p><p><strong>Conclusions: </strong>Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-β1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/6c/10.1177_11772719221135443.PMC9643117.pdf","citationCount":"5","resultStr":"{\"title\":\"The Prognostic Value of Lung Injury and Fibrosis Markers, KL-6, TGF-β1, FGF-2 in COVID-19 Patients.\",\"authors\":\"Hazan Karadeniz, Aslıhan Avanoğlu Güler, Hasan Selçuk Özger, Pınar Aysert Yıldız, Gonca Erbaş, Gülendam Bozdayı, Tuba Deveci Bulut, Özlem Gülbahar, Dilek Yapar, Hamit Küçük, Mehmet Akif Öztürk, Abdurrahman Tufan\",\"doi\":\"10.1177/11772719221135443\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-β1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19.</p><p><strong>Methods: </strong>Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-β1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed.</p><p><strong>Results: </strong>Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, <i>P</i> = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis.</p><p><strong>Conclusions: </strong>Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-β1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.</p>\",\"PeriodicalId\":47060,\"journal\":{\"name\":\"Biomarker Insights\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2022-11-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/6c/10.1177_11772719221135443.PMC9643117.pdf\",\"citationCount\":\"5\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomarker Insights\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/11772719221135443\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomarker Insights","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/11772719221135443","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 5
摘要
背景:肺损伤和间质纤维化的生物标志物有助于了解众所周知的间质性肺疾病(ILD)的受累程度和预后。血清Krebs von den Lungen-6 (KL-6)反映肺泡直接损伤，转化生长因子-β1 (TGF-β1)和成纤维细胞生长因子-2 (FGF-2)是ILD和几乎所有纤维化疾病纤维化的主要介质。从这个意义上说，我们旨在评估这些生物标志物与传统炎症标志物和COVID-19临床病程的相关性。方法:纳入经SARS-CoV-2核酸RT-PCR确诊的COVID-19患者，在确诊后1个月采用标准化方法进行前瞻性随访。根据美国国立卫生研究院的标准，将患者分为重症组和非重症组。结果评估重症监护病房(ICU)入院需求、长期呼吸支持和死亡。入组时采集血样，ELISA法检测血清中KL-6、TGF-β1、FGF-2水平。分析这些指标与其他预后指标及预后的关系。结果:共纳入31例重症和28例非重症COVID-19患者，并与健康对照组(n = 30)进行比较。COVID-19患者血清KL-6水平显著升高(中位数[IQR];11.54 [4.86] vs 8.54 [3.98] ng/mL, P = .001]， FGF-2水平较低(中位数[IQR];76.84 [98.2] vs 101.62 [210.6] pg/mL)。KL-6值与CRP、纤维蛋白原、d-二聚体和淋巴细胞计数有显著相关性。然而，我们没有发现这些标志物与随后的COVID-19严重程度、死亡率和长期预后之间的关联。结论:血清KL-6水平在COVID-19诊断时显著升高，并与其他传统预后炎症指标有良好的相关性。血清主要纤维化介质TGF-β1、FGF-2在COVID-19诊断时未升高，因此无助于预测长期预后。
The Prognostic Value of Lung Injury and Fibrosis Markers, KL-6, TGF-β1, FGF-2 in COVID-19 Patients.
Background: Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-β1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19.
Methods: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-β1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed.
Results: Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, P = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis.
Conclusions: Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-β1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.
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