Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
J Appl Lab Med. 2022 Sep 1;7(5):1169-1174. doi: 10.1093/jalm/jfac034.
The objective of this analysis was to compare the performance sensitivity and specificity of manufacturer-recommended signal-to-cutoff (S/Co) thresholds with modified S/Co values to estimate the prevalence of SARS-CoV-2-specific antibodies in a cohort of firefighters with a known infection history.
Plasma venipuncture samples were used for serologic analysis of firefighters in Los Angeles, CA, USA, in October 2020. Seropositivity was assessed using the manufacturer's recommended S/Co (≥1.4 IgG) and modified S/Co thresholds based on measured antibody levels in 178 negative control patients who had blood drawn prior to the emergence of COVID-19. Optimal S/Co threshold was determined by receiver operating characteristic (ROC) curve analysis.
Of 585 firefighters included in the study, 52 (8.9%) reported having a PCR-positive test history prior to antibody testing. Thirty-five (67.3%) firefighters with a previous PCR-positive test were seropositive based on the manufacturer S/Co thresholds, consistent with an estimated 67.3% sensitivity and 100% specificity. After evaluating multiple modified S/Co thresholds based on pre-pandemic negative samples, a modified S/Co of 0.36 was found to yield optimal sensitivity (88.5%) and specificity (99.4%) by ROC curve analysis. This modified threshold improved serostatus classification accuracy by 21.2%.
S/Co thresholds based on known negative samples significantly increase seropositivity and more accurately estimate cumulative incidence of disease compared to manufacturer-based thresholds.
本分析的目的是比较制造商推荐的信号与截止值（S/Co）阈值与修改后的 S/Co 值的性能灵敏度和特异性，以评估具有已知感染史的消防员队列中 SARS-CoV-2 特异性抗体的流行率。
2020 年 10 月，在美国加利福尼亚州洛杉矶，使用血浆静脉穿刺样本对消防员进行血清学分析。使用制造商推荐的 S/Co（≥1.4 IgG）和基于 178 名在 COVID-19 出现之前采血的阴性对照患者测量的抗体水平的修改后的 S/Co 阈值来评估血清阳性。通过接受者操作特征（ROC）曲线分析确定最佳 S/Co 阈值。
在纳入研究的 585 名消防员中，52 名（8.9%）报告在抗体检测前有 PCR 阳性检测史。根据制造商 S/Co 阈值，35 名（67.3%）先前 PCR 阳性的消防员血清阳性，估计敏感性为 67.3%，特异性为 100%。在评估了多个基于大流行前阴性样本的修改后的 S/Co 阈值后，通过 ROC 曲线分析发现修改后的 S/Co 为 0.36 可获得最佳的敏感性（88.5%）和特异性（99.4%）。该修改后的阈值将血清阳性状态分类的准确性提高了 21.2%。
与基于制造商的阈值相比，基于已知阴性样本的 S/Co 阈值可显著提高血清阳性率，并更准确地估计疾病的累积发病率。
