对SARS-CoV-2的抗体反应是评估病毒在人群中的传播和评估候选疫苗的有价值的生物标志物。最近的数据表明,抗体水平在COVID-19中也可能具有预后意义。到目前为止,大多数血清学研究都依赖于测试针对刺突(S)或核衣壳(N)蛋白的抗体,然而,抗体可以针对病毒的其他结构和非结构蛋白,而它们的频率,生物学和临床意义未知。
开发了包含30种SARS-CoV-2抗原或其片段的新型抗原阵列,用于检测IgG,IgA,来自103例COVID-19患者的血清中对SARS-CoV-2的IgE和IgM反应,其中包括34例患者,和20个大流行前健康对照。
对各种抗原的抗体应答是高度相关的,并且在患有严重/中度疾病的患者中抗体的频率和峰值水平高于患有轻度疾病的患者。这一发现支持了抗SARS-CoV-2抗体可能通过抗体依赖性增强而加剧疾病严重程度的观点。此外,对全长S蛋白的早期IgG和IgA反应可用作鉴定有严重疾病风险的患者的额外生物标志物.重要的是,这是首次报道SARS-CoV-2引起IgE应答的研究,其血清水平与疾病的严重程度呈正相关,因此提示高水平抗体与肥大细胞活化之间存在联系.
这是第一项评估IgG患病率和动力学的研究,IgA,IgE和IgM同时应答多种SARS-CoV-2抗原。结果为COVID-19的发病机制提供了重要见解,并对规划和解释基于抗体的流行病学研究具有重要意义。
Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown.
A novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls.
Antibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation.
This is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.