Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
BMC Infect Dis. 2021 Feb 18;21(1):187. doi: 10.1186/s12879-021-05878-2.
Thresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. In this setting the sensitivity and specificity of the best performing assays can both exceed 98%. However, antibody assay performance following mild infection is less clear.
We assessed quantitative IgG responses in a cohort of healthcare workers in Oxford, UK, with a high pre-test probability of Covid-19, in particular the 991/11,475(8.6%) who reported loss of smell/taste. We use anosmia/ageusia and other risk factors as probes for Covid-19 infection potentially undiagnosed by immunoassays by investigating their relationship with antibody readings either side of assay thresholds.
The proportion of healthcare workers reporting anosmia/ageusia increased at antibody readings below diagnostic thresholds using an in-house ELISA (n = 9324) and the Abbott Architect chemiluminescent microparticle immunoassay (CMIA; n = 11,324): 426/906 (47%) reported anosmia/ageusia with a positive ELISA, 59/449 (13.1%) with high-negative and 326/7969 (4.1%) with low-negative readings. Similarly, by CMIA, 518/1093 (47.4%) with a positive result reported anosmia/ageusia, 106/686 (15.5%) with a high-negative and 358/9563 (3.7%) with a low-negative result. Adjusting for the proportion of staff reporting anosmia/ageusia suggests the sensitivity of both assays in mild infection is lower than previously reported: Oxford ELISA 89.8% (95%CI 86.6-92.8%) and Abbott CMIA 79.3% (75.9-82.7%).
Following mild SARS-CoV-2 infection 10-30% of individuals may have negative immunoassay results. While lowered diagnostic thresholds may result in unacceptable specificity, our findings have implications for epidemiological analyses and result interpretation in individuals with a high pre-test probability. Samples from mild PCR-confirmed infections should be included in SARS-CoV-2 immunoassay evaluations.
SARS-CoV-2 抗体检测的阈值通常是使用来自有症状、常住院的患者的样本确定的。在这种情况下，表现最好的检测方法的灵敏度和特异性都可以超过 98%。然而，轻度感染后抗体检测的性能尚不清楚。
我们评估了英国牛津的一组有高新冠病毒感染先验概率的医护人员的定量 IgG 反应，特别是报告嗅觉/味觉丧失的 991/11475 人（8.6%）。我们使用嗅觉丧失/味觉丧失和其他风险因素作为免疫检测可能未诊断的新冠病毒感染的探针，通过调查它们与检测阈值两侧的抗体读数的关系来研究它们的关系。
使用内部 ELISA（n=9324）和雅培 Architect 化学发光微粒子免疫测定（CMIA；n=11324），报告嗅觉丧失/味觉丧失的医护人员比例在抗体读数低于诊断阈值时增加：906 例 ELISA 阳性中有 426 例（47%），高阴性中有 59 例（13.1%），低阴性中有 326 例（79%）。同样，通过 CMIA，1093 例阳性结果中有 518 例（47.4%）报告嗅觉丧失/味觉丧失，高阴性中有 106 例（15.5%），低阴性中有 358 例（9563 例中的 3.7%）。调整报告嗅觉丧失/味觉丧失的员工比例表明，两种检测方法在轻度感染中的灵敏度都低于先前报道的水平：牛津 ELISA 89.8%（95%CI 86.6-92.8%）和雅培 CMIA 79.3%（75.9-82.7%）。
在轻度 SARS-CoV-2 感染后，10-30%的个体可能有阴性免疫检测结果。虽然降低诊断阈值可能会导致不可接受的特异性，但我们的发现对具有高先验概率的个体的流行病学分析和结果解释有影响。应将来自轻度 PCR 确诊感染的样本纳入 SARS-CoV-2 免疫检测评估。
