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Ultrasensitive high-resolution profiling of early seroconversion in patients with COVID-19.
Nature Biomedical Engineering ( IF 28.1 ) Pub Date : 2020-09-18 , DOI: 10.1038/s41551-020-00611-x
Maia Norman 1, 2, 3 , Tal Gilboa 1, 2, 4 , Alana F Ogata 1, 2, 4 , Adam M Maley 1, 2, 4 , Limor Cohen 1, 2, 5 , Evan L Busch 6 , Roey Lazarovits 1, 2, 4 , Chih-Ping Mao 1, 4 , Yongfei Cai 7 , Jun Zhang 7 , Jared E Feldman 8 , Blake M Hauser 8 , Timothy M Caradonna 8 , Bing Chen 7, 9 , Aaron G Schmidt 8, 10 , Galit Alter 8 , Richelle C Charles 11, 12 , Edward T Ryan 11, 12, 13 , David R Walt 1, 2, 4
Affiliation  

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 µl 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.



中文翻译:

COVID-19 患者早期血清转化的超灵敏高分辨率分析。

灵敏的检测对于准确识别感染严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的个体至关重要。在这里,我们报告了一种基于荧光的多路检测方法,用于检测感染个体中少于 1 µl 的血液中的血清转化,最早可在症状出现后第一次核酸检测呈阳性的当天进行。该测定使用染料编码的抗原包被的珠子来量化针对四种 SARS-CoV-2 抗原的免疫球蛋白 G (IgG)、IgM 和 IgA 抗体的水平。使用在大流行期间收集的样本和在 2019 年冠状病毒病 (COVID-19) 首次爆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盲验证队列中检测血清转化的准确率为 99%在大流行之前和从 COVID-19 患者身上收集的样本,在通过 PCR 和逆转录进行鼻咽检测呈阳性后 5 天或更长时间。COVID-19 患者的高通量血清学分析允许询问抗体同种型和病毒蛋白之间的相互作用,并应帮助我们了解临床表现的异质性。

更新日期:2020-09-20
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