ABSTRACT

In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, multiple diagnostic tests are required for acute disease diagnosis, contact tracing, monitoring asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed. Unlike PCR tests which are highly specific, cross-reactivity is a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. SARS-CoV is genetically related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus in the genus Betacoronavirus of family Coronaviridae. We developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. There is significant cross-reactivity when N protein of either virus is used. The S1 or RBD regions from the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. We found that SARS survivors all have significant levels of antibodies remaining in their blood 17 years after infection. Anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.

摘要

为了应对由SARS-CoV-2引起的2019年冠状病毒疾病（COVID-19）爆发，需要进行多种诊断测试才能诊断急性疾病，接触追踪，监测无症状感染率并评估牛群免疫力。尽管PCR仍然是急性诊断环境中首选的一线检测方法，但迫切需要进行血清学检测。与高度特异性的PCR测试不同，考虑到已知还有其他六种冠状病毒感染人类，交叉反应是COVID-19抗体测试的主要挑战。SARS冠状病毒的基因与非典冠状病毒-2共享约80％的序列同一性和同属种SARS冠状病毒相关的属乙型家族的冠状。我们开发并比较了四种不同血清学检测的性能，以全面评估COVID-19与SARS患者血清之间的交叉反应性。当使用两种病毒的N蛋白时，存在明显的交叉反应。穗蛋白（S）的S1或RBD区具有更好的特异性。在不同平台中，捕获ELISA表现最佳。我们发现，SARS幸存者在感染后17年的血液中均残留有显着水平的抗体。抗N抗体的抗性要强于抗RBD的抗体，而后者在提供保护性免疫方面起着更重要的作用。