SARS-CoV-2 nucleocapsid and RT-PCR results

We collected blood samples from patients admitted to the hospital during a
period with RT-PCR based-screening of patients for Severe Acute
Respiratory Syndrome Cornavirus-2 (SARS-CoV-2). Retrospectively the
SARS-CoV-2 nucleocapsid protein (NP) plasma concentrations were measured
with an ELISA method and used for an initial time course study to find the
optimal time-point for sampling blood. Next, we estimated the diagnostic
accuracy i.e. the clinical sensitivity and specificity at different plasma
NP cut-off concentrations. The time course study revealed profiles with
rapid or more slow declines in NP titers after the RT-PCR result.
Nevertheless, in the time interval 0 – 7 days after the RT-PCR result, the
NP concentration was always above the level of detection at 1.66 pg/ml
suggesting that the diagnosis could be established in the time interval of
0 - 7 days. The median time gap between the plasma NP and RT-PCR results
was 0.0 days (n = 1957, interval: -26 to + 21 days). Reducing the time gap
to seven days, the clinical sensitivity was 90.0% (n= 60, 95% CI, 82.4% to
97.6%) at a specificity of 95.9% (n=1876, 95% CI, 95.0% to 96.8%). Curve
analysis by receiver operation characteristics identified a cut-off
concentration of 1.87 pg/mL NP as optimal resulting in a positive
predictive value of 41.2%, a negative predictive value of 99.7% and a
prevalence of 3.1%. In conclusion, the NP method is acceptable for making
the laboratory diagnosis of SARS-CoV-2, and an intended use of plasma NP
as a prospective nosocomial screening method is considered feasible.

我们收集了某一时期因严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）接受基于RT-PCR筛查的住院患者血液样本。回顾性采用酶联免疫吸附试验（ELISA）方法测定患者血浆中SARS-CoV-2核衣壳蛋白（NP）浓度，并通过初步时间进程研究确定最佳采血时间点。随后，我们评估了不同血浆NP临界浓度下的诊断准确性，即临床敏感性和特异性。时间进程研究显示，RT-PCR结果后NP滴度呈现快速或较缓慢下降的变化曲线。然而，在RT-PCR检测结果后的0-7天时间区间内，NP浓度始终高于1.66 pg/ml的检测限，表明可在此区间内确立诊断。血浆NP检测结果与RT-PCR结果之间的中位时间差为0.0天（n=1957，区间：-26至+21天）。将时间差缩短至7天时，临床敏感性为90.0%（n=60，95%置信区间（95% CI）：82.4%至97.6%），特异性为95.9%（n=1876，95%置信区间（95% CI）：95.0%至96.8%）。受试者工作特征曲线（ROC曲线）分析确定1.87 pg/mL的NP临界浓度为最优，其对应的阳性预测值为41.2%、阴性预测值为99.7%、患病率为3.1%。综上，NP检测方法可用于SARS-CoV-2的实验室诊断，且血浆NP作为前瞻性院内筛查方法的预期用途被认为是可行的。