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中国北京一家三级甲等医院中新冠病毒肺炎患者抗体反应的纵向分析

Longitudinal Profiling of Antibody Response in Patients With COVID-19 in a Tertiary Care Hospital in Beijing, China.

作者信息

Feng Xia, Yin Jiming, Zhang Jiaying, Hu Yaling, Ouyang Yabo, Qiao Shubin, Zhao Hong, Zhang Tong, Li Xuemei, Zhang Lili, Zhang Jie, Jin Ronghua, Feng Yingmei, Su Bin

机构信息

Beijing Youan Hospital, Capital Medical University, Beijing, China.

Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

出版信息

Front Immunol. 2021 Mar 15;12:614436. doi: 10.3389/fimmu.2021.614436. eCollection 2021.

Abstract

The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of the coronavirus disease 2019 (COVID-19), which elicits a wide variety of symptoms, ranging from mild to severe, with the potential to lead to death. Although used as the standard method to screen patients for SARS-CoV-2 infection, real-time PCR has challenges in dealing with asymptomatic patients and those with an undetectable viral load. Serological tests are therefore considered potent diagnostic tools to complement real-time PCR-based diagnosis and are used for surveillance of seroprevalence in populations. However, the dynamics of the antibody response against SARS-CoV-2 currently remain to be investigated. Here, through analysis of plasma samples from 84 patients with COVID-19, we observed that the response of virus-specific antibodies against three important antigens, RBD, N and S, dynamically changed over time and reached a peak 5-8 weeks after the onset of symptoms. The antibody responses were irrespective of sex. Severe cases were found to have higher levels of antibody response, larger numbers of inflammatory cells and C-reactive protein levels. Within the mild/moderate cases, pairwise comparison indicated moderate association between anti-RBD vs. anti-N, anti-RBD vs. anti-S1S2, and anti-N vs. anti-S1S2. Furthermore, the majority of cases could achieve IgM and IgG seroconversion at 2 weeks since the disease onset. Analysis of neutralizing antibodies indicated that these responses were able to last for more than 112 days but decline significantly after the peak. In summary, our findings demonstrate the longitudinally dynamic changes in antibody responses against SARS-CoV-2, which can contribute to the knowledge of humoral immune response after SARS-CoV-2 infection and are informative for future development of vaccine and antibody-based therapies.

摘要

新型冠状病毒严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引发了2019年冠状病毒病(COVID-19)的全球大流行,该疾病引发了从轻度到重度的各种症状,甚至有导致死亡的可能。尽管实时荧光定量聚合酶链反应(real-time PCR)被用作筛查SARS-CoV-2感染患者的标准方法,但在处理无症状患者和病毒载量检测不到的患者时存在挑战。因此,血清学检测被认为是补充基于实时荧光定量聚合酶链反应诊断的有效诊断工具,并用于人群血清流行率的监测。然而,目前针对SARS-CoV-2的抗体反应动态仍有待研究。在此,通过对84例COVID-19患者的血浆样本进行分析,我们观察到针对三种重要抗原RBD、N和S的病毒特异性抗体反应随时间动态变化,并在症状出现后5-8周达到峰值。抗体反应与性别无关。发现重症病例的抗体反应水平更高、炎症细胞数量更多且C反应蛋白水平更高。在轻症/中症病例中,两两比较表明抗RBD与抗N、抗RBD与抗S1S2以及抗N与抗S1S2之间存在中度关联。此外,大多数病例在发病后2周可实现IgM和IgG血清学转换。中和抗体分析表明,这些反应能够持续超过112天,但在达到峰值后显著下降。总之,我们的研究结果证明了针对SARS-CoV-2的抗体反应的纵向动态变化,这有助于了解SARS-CoV-2感染后的体液免疫反应,并为疫苗和基于抗体的治疗方法的未来发展提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0713/8005580/1c6e06a2b6b6/fimmu-12-614436-g0001.jpg

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