Ultra-Sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease
Ultra-Sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease
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DOI：
10.1093/clinchem/hvaa213
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发表时间：
2020-12-01
影响因子：
9.3
通讯作者：
Walt, David R.
中科院分区：
文献类型：
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作者：
Ogata, Alana F.;Maley, Adam M.;Walt, David R.
背景：自2020年8月16日以来，严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)已在全球范围内感染2100多万人。尽管SARS-CoV-2抗原检测方法具有识别活动性感染和监测疾病进展的潜力，但与聚合酶链式反应和血清学检测相比，仍不发达。方法：采用单分子阵列(SIMOA)方法定量检测新冠肺炎患者血浆中SARS-CoV-2尖峰蛋白、S1亚基和核衣壳抗原。我们研究了新冠肺炎阳性的患者、17名新冠肺炎阴性的患者和34名大流行前患者的血浆。我们结合SIMOA抗SARS-CoV-2血清学检测方法，对39例新冠肺炎患者272份纵向血浆标本中31个SARS-CoV-2生物标志物的变化进行了定量研究。结果：在新冠肺炎阳性患者中，41例检出SARS-CoV-2 S1和N抗原。在这些患者中，在血清转换后5+/-1天观察到血浆中抗原的完全清除，平均+/-95%可信区间，鼻咽RT-PCR试验在病毒抗原清除后15+/-5天报告阳性结果。结论：报道的SARS-CoV-2 SIMOA抗原检测方法首次在新冠肺炎阳性患者的血浆中检测到病毒抗原。这些数据表明，在患有严重疾病的新冠肺炎患者中，血液中的SARS-CoV-2病毒抗原与疾病进展有关，如呼吸衰竭。
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential to identify active infection and monitor disease progression.METHODS: We used Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of patients with coronavirus disease (COVID-19). We studied plasma from 64 patients who were COVID-19 positive, 17 who were COVID-19 negative, and 34 pre-pandemic patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we quantified changes in 31 SARS-CoV-2 biomarkers in 272 longitudinal plasma samples obtained for 39 patients with COVID-19. Data were analyzed by hierarchical clustering and were compared to longitudinal RT-PCR test results and clinical outcomes.RESULTS: SARS-CoV-2 S1 and N antigens were detectable in 41 out of 64 COVID-19 positive patients. In these patients, full antigen clearance in plasma was observed a mean +/- 95% CI of 5 +/- 1 days after seroconversion and nasopharyngeal RT-PCR tests reported positive results for 15 +/- 5 days after viral-antigen clearance. Correlation between patients with high concentrations of S1 antigen and ICU admission (77%) and time to intubation (within 1 day) was statistically significant.CONCLUSIONS: The reported SARS-CoV-2 Simoa antigen assay is the first to detect viral antigens in the plasma of patients who were COVID-19 positive to date. These data show that SARS-CoV-2 viral antigens in the blood are associated with disease progression, such as respiratory failure, in COVID-19 cases with severe disease.