Manufacturer Signal-to-Cutoff Threshold Underestimates Cumulative Incidence of SARS-CoV-2 Infection: Evidence from the Los Angeles Firefighters Study
Manufacturer Signal-to-Cutoff Threshold Underestimates Cumulative Incidence of SARS-CoV-2 Infection: Evidence from the Los Angeles Firefighters Study
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DOI：
10.1093/jalm/jfac034
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发表时间：
2022-06-04
影响因子：
2
通讯作者：
Sood, Neeraj
中科院分区：
文献类型：
--
作者：
Toubat, Omar;Berg, Anders H.;Sood, Neeraj
背景：本分析的目的是比较制造商建议的信号截止(S/Co)阈值和修改的S/Co值在估计有已知感染史的消防员中SARS-CoV-2特异性抗体流行率方面的敏感性和特异性。方法：2020年10月，采用血浆静脉穿刺法对美国加利福尼亚州洛杉矶的消防员进行血清学分析。根据测定的抗体水平，用制造商推荐的S/钴(>；=1.4Ig)和改良的S/钴阈值对178例阴性对照患者进行了血清阳性检测，这些患者在新冠肺炎出现之前曾抽血过。结果：在585名消防员中，52名(8.9%)在抗体检测前有聚合酶链式反应阳性史。根据制造商S/钴的阈值，35名(67.3%)有聚合酶链式反应阳性的消防员血清阳性，与估计的67.3%的敏感性和100%的特异性一致。根据疫情前阴性样本对多个修正的S/Co阈值进行评估后，通过ROC曲线分析发现，修正的S/Co为0.36的灵敏度(88.5%)和特异度(99.4%)是最佳的。这一改进的阈值将血清学分类的准确率提高了21.2%。结论：与制造商的阈值相比，基于已知阴性样本的S/Co阈值显著提高了血清阳性率，并更准确地估计了疾病的累积发病率。
Background: 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.Methods: 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.Results: 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%.Conclusions: S/Co thresholds based on known negative samples significantly increase seropositivity and more accurately estimate cumulative incidence of disease compared to manufacturer-based thresholds.