Kinetics of viral load and antibody response in relation to COVID-19 severity
Kinetics of viral load and antibody response in relation to COVID-19 severity
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DOI：
10.1172/jci138759
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发表时间：
2020-10-01
影响因子：
15.9
通讯作者：
Zhao, Jincun
中科院分区：
文献类型：
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作者：
Wang, Yanqun;Zhang, Lu;Zhao, Jincun
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是2019冠状病毒（COVID-19）肺炎的病原体。关于COVID-19患者的动力学、组织分布、交叉反应性和中和抗体反应，我们知之甚少。本研究纳入了两组经RT-PCR确诊的COVID-19患者：12名重症监护室需要机械通气的重症患者和11名隔离病房的轻症患者。采集系列临床样本进行实验室检测。结果显示，大多数重症患者在发病后20-40天内在各种组织中有病毒脱落（8/12，66.7%），而大多数轻度患者在发病后10天内病毒脱落仅限于呼吸道，并且未检测到病毒RNA（9/11，81.8%）。轻症组IgM抗体反应明显低于重症组。在发病后9天，在重度和轻度组的大多数患者中检测到IgG应答，并且在整个研究期间保持在高水平。在COVID-19患者中检测到与SARS-CoV和SARS-CoV-2交叉反应的抗体，但在MERS患者中未检测到。高水平的中和抗体诱导后约10天后，在严重和轻度疾病的患者，这是更高的严重组。SARS-CoV-2假型中和试验与真病毒减灶中和试验结果一致。来自COVID-19患者的血清抑制SARS-CoV-2进入。SARS或中东呼吸综合征（MERS）康复期患者的血清则没有。抗SARS-CoV-2S和NIgG水平与患者血浆中和滴度呈中度相关。这项研究提高了我们对SARS-CoV-2感染后人体免疫反应的理解。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus 2019 (COVID-19) pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity, and neutralization antibody response in patients with COVID-19. Two groups of patients with RT-PCR-confirmed COVID-19 were enrolled in this study: 12 severely ill patients in intensive care units who needed mechanical ventilation and 11 mildly ill patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severely ill patients had viral shedding in a variety of tissues for 20-40 days after onset of disease (8/12, 66.7%), while the majority of mildly ill patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA 10 days after onset (9/11, 81.8%). Mildly ill patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both the severe and mild groups at 9 days after onset, and remained at a high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in patients with COVID-19 but not in patients with MERS. High levels of neutralizing antibodies were induced after about 10 days after onset in both severely and mildly ill 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 patients with COVID-19 inhibited SARS-CoV-2 entry. Sera from convalescent patients with SARS or Middle East respiratory syndrome (MERS) did not. Anti-SARS-CoV-2 S and NIgG levels exhibited a moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in humans after SARS-CoV-2 infection.