Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Malaria Research and Training Center/University of Science, Techniques, and Technologies of Bamako, Bamako, Mali.
J Infect Dis. 2021 Dec 15;224(12):2001-2009. doi: 10.1093/infdis/jiab498.
False positivity may hinder the utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests in sub-Saharan Africa.
From 312 Malian samples collected before 2020, we measured antibodies to the commonly tested SARS-CoV-2 antigens and 4 other betacoronaviruses by enzyme-linked immunosorbent assay (ELISA). In a subset of samples, we assessed antibodies to a panel of Plasmodium falciparum antigens by suspension bead array and functional antiviral activity by SARS-CoV-2 pseudovirus neutralization assay. We then evaluated the performance of an ELISA using SARS-CoV-2 spike protein and receptor-binding domain developed in the United States using Malian positive and negative control samples. To optimize test performance, we compared single- and 2-antigen approaches using existing assay cutoffs and population-specific cutoffs.
Background reactivity to SARS-CoV-2 antigens was common in prepandemic Malian samples. The SARS-CoV-2 reactivity varied between communities, increased with age, and correlated negligibly/weakly with other betacoronavirus and P falciparum antibodies. No prepandemic samples demonstrated functional activity. Regardless of the cutoffs applied, test specificity improved using a 2-antigen approach. Test performance was optimal using a 2-antigen assay with population-specific cutoffs (sensitivity, 73.9% [95% confidence interval {CI}, 51.6-89.8]; specificity, 99.4% [95% CI, 97.7-99.9]).
We have addressed the problem of SARS-CoV-2 seroassay performance in Africa by using a 2-antigen assay with cutoffs defined by performance in the target population.
假阳性可能会降低严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）血清学检测在撒哈拉以南非洲的实用性。
我们从 2020 年前采集的 312 份马里样本中，通过酶联免疫吸附试验（ELISA）测量了常见 SARS-CoV-2 抗原和其他 4 种β冠状病毒的抗体。在部分样本中，我们通过悬浮珠阵列评估了针对一组恶性疟原虫抗原的抗体，并通过 SARS-CoV-2 假病毒中和试验评估了其抗病毒活性。然后，我们使用美国开发的基于 SARS-CoV-2 刺突蛋白和受体结合域的 ELISA 评估了马里阳性和阴性对照样本的性能。为了优化测试性能，我们使用现有的检测截止值和特定人群的截止值比较了单抗原和双抗原方法。
在流行前的马里样本中，对 SARS-CoV-2 抗原的背景反应很常见。SARS-CoV-2 的反应性在社区之间有所不同，随年龄增长而增加，与其他β冠状病毒和恶性疟原虫抗体的相关性可以忽略不计/较弱。没有流行前的样本显示出功能活性。无论应用哪种截止值，双抗原方法的检测特异性都有所提高。使用具有人群特异性截止值的双抗原检测（敏感性为 73.9%[95%置信区间{CI}，51.6-89.8%]；特异性为 99.4%[95%CI，97.7-99.9%]），检测性能最佳。
我们通过使用具有目标人群中性能定义的双抗原检测和截止值解决了 SARS-CoV-2 血清学检测在非洲的性能问题。
