【前沿速递】重磅！我国科学家阐明新型肺炎患者疾病严重程度与抗体反应的相关性

2020-07-09

近日，在钟南山院士的指导下，呼吸疾病国家重点实验室赵金存教授团队与清远市人民医院、阳江市人民医院、香港大学巴斯德研究所、广东省CDC等单位合作，发现新冠肺炎（COVID-19）病人的疾病严重程度（重症ICU病人和轻症病人）与病毒排毒特征和抗体反应存在明显的相关性和群体差异，为COVID-19病人的诊断和救治提供重要指导信息。相关成果发表于著名的《Journal of Clinical Investigation》杂志。

研究详细分析了轻、重症新冠病人的病毒排毒和抗体诱导情况。发现大部分ICU病人表现出较长排毒时间（20-40d），且排毒部位多样化（呼吸道样品、粪便、尿液、血液等），而轻症病人排毒一般仅局限于呼吸道样品，且10d后基本检测不到病毒；轻、重症患者均可以诱导较强的病毒特异性IgG反应，但轻症患者产生的IgM反应普遍较低，提示轻症患者IgM为主的血清学诊断要注意假阴性情况；进一步研究发现，重症患者的尿液、痰液、胸水、BALF等样品中检测到较高病毒特异性抗体，暗示重症患者存在多器官损伤，可作为重症标志物，为临床医生诊治提供参考。

另外轻、重症患者体内在发病后均可以诱导高水平的中和抗体；SARS-CoV与SARS-CoV-2存在明显的双向交叉抗体，但SARS-CoV康复者血浆对SARS-CoV-2病毒没有明显的中和作用，表明SARS康复者不一定对新冠病毒感染具有免疫保护；此外，也发现不同的病毒免疫蛋白诱导抗体水平在发病早期有一定的差异，需要选择合适的免疫蛋白检测。SARS-CoV-2与MERS-CoV没有明显的交叉反应，排除了血清学诊断将MERS患者与新冠感染混淆的可能性，对中东地区同时流行两种高致病冠状病毒的国家，具有重要的鉴别诊断意义；SARS-CoV-2病毒S、N蛋白诱导的特异性结合抗体与病毒中和抗体滴度之间存在明显的正相关，可用于临床诊治过程中初步判断患者体内中和抗体的产生和水平。

新型冠状病毒SARS-CoV-2是2019年年底发现的第7种人感染冠状病毒，致病性强，人间传播快，截止2020年7月上旬已感染1100多万人，病死50多万人。阐明新冠患者体液免疫应答特征，对解析新冠病毒致病机制，指导临床诊治，开发应急救治抗体和疫苗，从而降低新冠肺炎发病率、重症化率和死亡率具有重要意义。

广州医科大学附属第一医院王延群副教授、附属市八医院张璐博士、广医附一院ICU桑岭副主任、叶枫主任、阳江市人民医院阮世冲博士、清远市人民医院钟备博士、广东省CDC宋铁副主任、沙特Abeer Alshukairi教授、深圳市人民医院陈荣昌教授等为共同第一作者；广州医科大学赵金存教授、黎毅敏教授、肇静娴教授、香港大学Malik Peiris教授等为并列通讯，该项目获得国家重大专项、科技部新型冠状病毒专项、广东省新型冠状病毒专项等项目支持。

附文献信息：

题目：Kinetics of viral load and antibody response in relation to COVID-19 severity

DOI：10.1172/JCI138759

摘要：The SARS-CoV-2 is the causative agent for COVID-19 pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response in COVID-19 patients. Two groups of RT-PCR confirmed COVID-19 patients were enrolled in this study, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severe patients had viral shedding in a variety of tissues for 20~40 days post onset of disease (8/12, 66.7%); while the majority of mild patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA after 10 days post-onset (9/11, 81.8%). Mild patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in COVID-19 patients but not in MERS patients. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry. Anti-SARS-CoV-2 S and N IgG level exhibited moderate correlation with neutralization titers in patients’ plasma. This study improves our understanding of immune response in human after SARS-CoV-2 infection.