Sánchez-Díez Silvia, Gómez-Ollés Carlos, Cruz María-Jesús, de Homdedeu Miquel, Espejo David, Ferrer Jaume, Roca Oriol, Pacheco Andrés, Muñoz Xavier
Pulmonology Service, Department of Medicine, Vall d'Hebron University Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain.
CIBER of Respiratory Diseases (CIBERES), 28029 Madrid, Spain.
Curr Issues Mol Biol. 2023 Mar 1;45(3):1998-2012. doi: 10.3390/cimb45030128.
The aim of this study was to analyze biomarkers that might predict the severity and progression of the SARS-CoV-2 infection, both in the acute phase and after recovery.
Unvaccinated patients infected with the original strain of COVID-19 requiring ward (Group 1, n = 48) or ICU (Group 2, n = 41) admission were included. At the time of admission (visit 1), a clinical history was acquired, and blood samples were obtained. One and six months after discharge from the hospital (visits 2 and 3, respectively), a clinical history, lung function tests, and blood samples were carried out. At visit 2, patients also underwent a chest CT scan. Different cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, G-CSF, GM-CSF, IFN-ɣ, MCP-1, MIP-1β, and TNF-α) and lung fibrosis biomarkers (YKL-40 and KL-6) were measured in blood samples obtained at visits 1, 2, and 3.
At visit 1, IL-4, IL-5, and IL-6 levels were higher in Group 2 ( = 0.039, 0.011, and 0.045, respectively), and IL-17 and IL-8 levels were higher in Group 1 ( = 0.026 and 0.001, respectively). The number of patients in Groups 1 and 2 who died during hospitalization was 8 and 11, respectively. YKL-40 and KL-6 levels were higher in patients who died. Serum YKL-40 and KL-6 levels determined at visit 2 correlated negatively with FVC ( = 0.022 and = 0.024, respectively) and FEV1 ( = 0.012 and = 0.032, respectively) measured at visit 3. KL-6 levels also correlated negatively with the diffusing capacity of the lungs for carbon monoxide (DLCO, = 0.001).
Patients who required ICU admission had higher levels of Th2 cytokines, while patients admitted to the ward showed an innate immune response activation, with IL-8 release and Th1/Th17 lymphocyte contribution. Increased levels of YKL-40 and KL-6 were associated with mortality in COVID-19 patients.
本研究的目的是分析可能预测严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染在急性期及康复后严重程度和进展的生物标志物。
纳入未接种疫苗、感染新冠病毒原始毒株且需要入住病房(第1组,n = 48)或重症监护病房(ICU,第2组,n = 41)的患者。入院时(第1次就诊),获取临床病史并采集血样。出院后1个月和6个月(分别为第2次和第3次就诊),进行临床病史采集、肺功能测试并采集血样。在第2次就诊时,患者还接受了胸部CT扫描。在第1次、第2次和第3次就诊时采集的血样中检测不同的细胞因子(白细胞介素-1β、白细胞介素-2、白细胞介素-4、白细胞介素-5、白细胞介素-6、白细胞介素-7、白细胞介素-8、白细胞介素-10、白细胞介素-12p70、白细胞介素-13、白细胞介素-17A、粒细胞集落刺激因子、粒细胞-巨噬细胞集落刺激因子、干扰素-γ、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1β和肿瘤坏死因子-α)以及肺纤维化生物标志物(YKL-40和KL-6)。
在第1次就诊时,第2组的白细胞介素-4、白细胞介素-5和白细胞介素-6水平较高(分别为P = 0.039、0.011和0.045),第1组的白细胞介素-17和白细胞介素-8水平较高(分别为P = 0.026和0.001)。第1组和第2组在住院期间死亡的患者人数分别为8例和11例。死亡患者的YKL-40和KL-6水平较高。在第2次就诊时测定的血清YKL-40和KL-6水平与在第3次就诊时测定的用力肺活量(FVC,分别为P = 0.022和P = 0.024)和第1秒用力呼气量(FEV1,分别为P = 0.012和P = 0.032)呈负相关。KL-6水平也与肺一氧化碳弥散量(DLCO,P = 0.001)呈负相关。
需要入住ICU的患者Th2细胞因子水平较高,而入住病房的患者表现出先天性免疫反应激活,伴有白细胞介素-8释放以及Th1/Th细胞17淋巴细胞的作用。YKL-40和KL-6水平升高与新冠病毒感染患者的死亡率相关。