The Antibody Response to SARS-CoV-2 Infection
The Antibody Response to SARS-CoV-2 Infection
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DOI：
10.1093/ofid/ofaa387
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发表时间：
2020-09-01
影响因子：
4.2
通讯作者：
O'Sullivan, Matthew V. N.
中科院分区：
文献类型：
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作者：
Hueston, Linda;Kok, Jen;O'Sullivan, Matthew V. N.
背景检测严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）特异性抗体已成为一种重要工具，补充了核酸检测（NAT），用于诊断和确定人群血清调查中2019冠状病毒病（COVID-19）的患病率。抗体应答的幅度和持续性对于评估免疫持续时间至关重要。开发了一种SARS-CoV-2特异性免疫荧光抗体（IFA）检测免疫球蛋白G（IgG）、免疫球蛋白A（伊加）和免疫球蛋白M（IgM）的方法，并通过与NAT参比标准品比较，对疑似COVID-19患者的呼吸道样本进行了前瞻性评价。使用标准的微量中和试验在一个样本子集中测量中和抗体应答。共有2753人有资格参加这项研究（126 NAT阳性，患病率为4.6%）。从发病到出现抗体的中位“窗口期”（范围）为10.2（5.8-14.4）天。在症状发作后≥ 14天收集SARS-CoV-2 IgG、伊加或IgM的敏感性和特异性分别为91.3%（95%CI，84.9%-95.6%）和98.9%（95%CI，98.4%-99.3%）。阴性预测值为99.6%（95%CI，99.3%-99.8%）。检测任何抗体类别的阳性预测值为79.9%（95%CI，73.3%-85.1%）; IgG和IgA联合检测的阳性预测值增加至96.8%（95%CI，90.796-99.0%）。通过IFA测量SARS-CoV-2特异性抗体是诊断COVID-19的准确方法。应将血清学检测纳入SARS-CoV-2感染的诊断算法，以确定未进行NAT的其他病例，并解决疑似NAF假阴性和假阳性的病例。大多数个体在感染后产生强烈的抗体应答，但这些应答的持续时间和对免疫的影响仍有待确定。
Background. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies has become an important tool, complementing nucleic acid tests (NATs) for diagnosis and for determining the prevalence of coronavirus disease 2019 (COVID-19) in population serosurveys. The magnitude and persistence of antibody responses are critical for assessing the duration of immunity.Methods. A SARS-CoV-2-specific immunofluorescent antibody (IFA) assay for immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) was developed and prospectively evaluated by comparison to the reference standard of NAT on respiratory tract samples from individuals with suspected COVID-19. Neutralizing antibody responses were measured in a subset of samples using a standard microneutralization assay.Results. A total of 2753 individuals were eligible for the study (126 NAT-positive; prevalence, 4.6%). The median "window period" from illness onset to appearance of antibodies (range) was 10.2 (5.8-14.4) days. The sensitivity and specificity of either SARS-CoV-2 IgG, IgA, or IgM when collected >= 14 days after symptom onset were 91.3% (95% CI, 84.9%-95.6%) and 98.9% (95% CI, 98.4%-99.3%), respectively. The negative predictive value was 99.6% (95% CI, 99.3%-99.8%). The positive predictive value of detecting any antibody class was 79.9% (95% CI, 73.3%-85.1%); this increased to 96.8% (95% CI, 90.796-99.0%) for the combination of IgG and IgA.Conclusions. Measurement of SARS-CoV-2-specific antibody by IFA is an accurate method to diagnose COVID-19. Serological testing should be incorporated into diagnostic algorithms for SARS-CoV-2 infection to identify additional cases where NAT was not performed and resolve cases where false-negative and false-positive NAFs are suspected. The majority of individuals develop robust antibody responses following infection, but the duration of these responses and implications for immunity remain to be established.