Ultrasensitive high-resolution profiling of early seroconversion in patients with COVID-19
Ultrasensitive high-resolution profiling of early seroconversion in patients with COVID-19
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DOI：
10.1038/s41551-020-00611-x
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发表时间：
2020-09-18
影响因子：
28.1
通讯作者：
Walt, David R.
中科院分区：
文献类型：
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作者：
Norman, Maia;Gilboa, Tal;Walt, David R.
多路荧光法检测SARS-CoV-2感染者早在症状出现后第一次鼻咽核酸检测呈阳性的当天，从1 μ l以下的血液中检测血清转化。灵敏的检测方法对于准确识别严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染者至关重要。在这里，我们报告了一种基于荧光的多重检测方法，用于从少于1 μ l的血液中检测感染者的血清转化，并且早在症状出现后第一次核酸检测阳性的当天。该检测使用染料编码的抗原包被珠来量化针对四种SARS-CoV-2抗原的免疫球蛋白G （IgG）、IgM和IgA抗体的水平。使用大流行期间收集的样本、2019冠状病毒病（COVID-19）首次暴发前从健康个体和呼吸道感染患者收集的样本训练的逻辑回归模型，在大流行前收集的样本和通过反转录PCR检测鼻咽试验阳性5天或更长时间后的COVID-19患者的样本进行盲法验证队列中，检测血清转化的准确率为99%。COVID-19患者的高通量血清学分析允许询问抗体同型和病毒蛋白之间的相互作用，并有助于我们了解临床表现的异质性。
A multiplexed fluorescence-based assay detects seroconversion in individuals infected with SARS-CoV-2 from less than 1 mu l of blood as early as the day of the first positive nasopharyngeal nucleic acid test after symptom onset.Sensitive assays are essential for the accurate identification of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we report a multiplexed assay for the fluorescence-based detection of seroconversion in infected individuals from less than 1 mu l of blood, and as early as the day of the first positive nucleic acid test after symptom onset. The assay uses dye-encoded antigen-coated beads to quantify the levels of immunoglobulin G (IgG), IgM and IgA antibodies against four SARS-CoV-2 antigens. A logistic regression model trained using samples collected during the pandemic and samples collected from healthy individuals and patients with respiratory infections before the first outbreak of coronavirus disease 2019 (COVID-19) was 99% accurate in the detection of seroconversion in a blinded validation cohort of samples collected before the pandemic and from patients with COVID-19 five or more days after a positive nasopharyngeal test by PCR with reverse transcription. The high-throughput serological profiling of patients with COVID-19 allows for the interrogation of interactions between antibody isotypes and viral proteins, and should help us to understand the heterogeneity of clinical presentations.