While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody response in serum is not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Whereas anti-CoV-2 IgA and IgM antibodies rapidly decayed, IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. In a surrogate neutralization ELISA (snELISA), neutralization activity peaks by 31-45 days PSO and slowly declines, though a clear drop is detected at the last blood draw (105-115 days PSO). Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that systemic and mucosal humoral IgG antibodies are maintained in the majority of COVID-19 patients for at least 3 months PSO. Based on their correlation with each other, IgG responses in saliva may serve as a surrogate measure of systemic immunity.

中文翻译：

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COVID-19患者对SARS-CoV-2抗原的粘膜与全身抗体反应

虽然已经在血液中广泛研究了对SARS-CoV-2的抗体反应，但对粘膜免疫反应及其与全身抗体水平的关系知之甚少。由于SARS-CoV-2最初在上呼吸道中复制，因此口腔中的抗体反应可能是影响感染过程的重要参数，但是尚不知道它与血清中的抗体反应如何相关。在这里，我们通过酶联免疫吸附测定（ELISA）剖析了血清（n = 496）和唾液中对SARS-CoV-2峰值蛋白（全长三聚体）及其受体结合域（RBD）的IgG，IgA和IgM反应（与阴性对照相比，急性和恢复期患者，经实验室诊断的COVID-19在症状发作后（PSO）的3-115天不等（n = 90）。在血清和唾液中很容易检测到抗CoV-2抗体反应，PSO在16-30天时达到了最高IgG水平。抗CoV-2 IgA和IgM抗体迅速衰减，而两种生物流体中的IgG抗体在PSO长达105天时仍保持相对稳定。在替代中和ELISA（snELISA）中，中和活性在PSO 31-45天达到峰值，然后缓慢下降，尽管在最后一次抽血（PSO 105-115天）检测到明显下降。最后，IgG，IgM和对血清中刺突和RBD的IgA反应程度较小，与匹配的唾液样本呈正相关。这项研究证实，大多数COVID-19患者的全身和粘膜体液IgG抗体在PSO至少维持3个月。基于它们之间的相互关系，唾液中的IgG应答可作为全身免疫的替代指标。