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《工程(英文)》 >> 2021年 第7卷 第7期 doi: 10.1016/j.eng.2021.04.015

新冠病毒肺炎抗体应答、细胞因子的动态变化及其与生存状况的关联 ——一项回顾性队列研究

a Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
b Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
c Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
d Department of Otolaryngology–Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

收稿日期: 2020-10-30 修回日期: 2021-04-15 录用日期: 2021-04-21 发布日期: 2021-05-18

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摘要

目前,患者感染严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)后,机体免疫状况随时间的纵向变化及其与临床结局的关联尚不明确。因此,我们致力于研究新冠病毒特异性抗体[免疫球蛋白G(IgG)和免疫球蛋白M(IgM)]随时间变化的特征,并分析特异性抗体、炎性细胞因子及其与新冠病毒肺炎(COVID-19,简称新冠肺炎)患者的生存状况之间的关联。研究共招募了1830例实验室确诊的新冠肺炎感染病例。利用局部加权回归散点平滑法(LOWESS)拟合患者自发病以来直至12周的病毒载量、特异性抗体及细胞因子水平随时间的变化谱。通过中介分析,探究细胞因子在抗体应答与生存状况之间的中介效应。在1830例患者中,新冠病毒核酸阳性患者共1435例,新冠病毒特异性IgG和(或)IgM抗体阳性患者为395例。在1435例患者中,2.4%的患者在住院期间既未出现IgG也未出现IgM的血清学转变。特异性IgG和IgM的血清阳性率在发病后的第1周分别为29.6%和48.1%,并在5周内达到峰值。对于痊愈出院患者组,在发病后的12周内,IgM水平缓慢下降,而IgG水平基本维持在188 AU· mL−1左右。反之,对于最终进展为死亡的患者,其IgM水平迅速下降,IgG水平在第12周也下降至87 AU· mL−1。与出院患者组相比,病亡患者组的白细胞介素6(IL-6)、白细胞介素8(IL-8)、白细胞介素10(IL-10)、白细胞介素1β(IL-1β)、白细胞介素2受体(IL-2R)及肿瘤坏死因子-α(TNF-α)水平均较高,IgG水平与死亡风险之间12.5%的关联由上述细胞因子介导。本研究阐明了新冠病毒特异性抗体自发病以来12周内的实时变化特征,并表明了抗体应答对生存结局的积极作用,相关发现对新冠肺炎患者的预后评估可能有所帮助。

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