Xiao Xiumei, Zhou Qingtao, Zhu Jinghao, Sun Lin, Zhang Hua, Sun Yongchang, Zhao Jinxia, Cui Liyan
The Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China.
The Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China.
Ann Transl Med. 2021 Apr;9(7):534. doi: 10.21037/atm-20-6509.
The outbreak of the novel 2019 coronavirus disease (COVID-19) was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020. The diagnosis of COVID-19 is frequently based on a positive serological test. We noted the occurrence of false-positive results for COVID-19 in the colloidal gold-based immunochromatographic strip (ICS) assay in sera from patients with autoimmune diseases (ADs). This study aimed to evaluate the possible reasons for the false-positive results in two ICS assays (Wondfo ICS and Innovita ICS) and to investigate the effect of urea dissociation in reducing false-positive results.
The sera of 135 patients with ADs, 13 confirmed COVID-19 patients, 95 disease controls, and 120 healthy controls were tested for immunoglobin M (IgM) and IgG against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using Wondfo and Innovita ICS kits. The distributions of auto-antibodies in antibody-positive and antibody-negative groups were also compared, and bivariable logistic regression was used to assess auto-antibodies associated with false-positive results. A urea dissociation test of ICS was performed for the SARS-CoV-2 antibody-positive samples.
Specificity of Wondfo ICS for the 95 disease controls was 94.74% compared to 98.95% and 96.84% for Innovita SARS-CoV-2 IgM and IgG, respectively. Specificity of Wondfo ICS for the 120 healthy controls was 97.5% compared to 100% and 99.17% for Innovita SARS-CoV-2 IgM and IgG, respectively. Specificity of Wondfo ICS for AD patients was 73.33% compared to 97.78% and 96.30% for Innovita SARS-CoV-2 IgM and IgG, respectively. Sensitivity was 74.07% for Wondfo compared to 70.37% for Innovita IgM and 66.67% for Innovita IgG. Using the Wondfo ICS, the percentage of elevated rheumatoid factor (RF) level (>20 IU/mL) was higher in the SARS-CoV-2 antibody-positive group compared with the antibody-negative group [27/36 (75.0%) . 34/99 (34.34%), P=0.001]. The elevated RF was associated with antibody positivity, with an odds ratio of 4.671 [95% confidence interval (CI), 1.88-11.69]. The specificity of the Wondfo ICS assay for the AD patients was increased from 73.33% to 94.07% after the urea dissociation assay.
An elevated serum RF level could lead to false-positive results when detecting SARS-CoV-2 antibodies using the Wondfo ICS kit, and the urea dissociation assay would be helpful in reducing the incidence of false-positive results.
2020年3月11日，世界卫生组织（WHO）宣布新型2019冠状病毒病（COVID-19）疫情为全球大流行。COVID-19的诊断通常基于血清学检测呈阳性。我们注意到自身免疫性疾病（AD）患者血清中基于胶体金免疫层析试纸条（ICS）检测COVID-19出现了假阳性结果。本研究旨在评估两种ICS检测方法（万孚ICS和英诺维他ICS）出现假阳性结果的可能原因，并研究尿素解离在减少假阳性结果方面的作用。
使用万孚和英诺维他ICS试剂盒，对135例AD患者、13例确诊的COVID-19患者、95例疾病对照者和120例健康对照者的血清进行针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的免疫球蛋白M（IgM）和IgG检测。还比较了抗体阳性组和抗体阴性组自身抗体的分布情况，并采用二元逻辑回归评估与假阳性结果相关的自身抗体。对SARS-CoV-2抗体阳性样本进行ICS的尿素解离试验。
万孚ICS对95例疾病对照者的特异性为94.74%，而英诺维他SARS-CoV-2 IgM和IgG的特异性分别为98.95%和96.84%。万孚ICS对120例健康对照者的特异性为97.5%，而英诺维他SARS-CoV-2 IgM和IgG的特异性分别为100%和99.17%。万孚ICS对AD患者的特异性为73.33%，而英诺维他SARS-CoV-2 IgM和IgG的特异性分别为97.78%和96.30%。万孚的灵敏度为74.07%，而英诺维他IgM为70.37%，英诺维他IgG为66.67%。使用万孚ICS，SARS-CoV-2抗体阳性组类风湿因子（RF）水平升高（>20 IU/mL）的百分比高于抗体阴性组[27/36（75.0%）对34/99（34.34%），P = 0.001]。RF升高与抗体阳性相关，比值比为4.671[95%置信区间（CI），1.88 - 11.69]。尿素解离试验后，万孚ICS检测AD患者的特异性从73.33%提高到94.07%。
使用万孚ICS试剂盒检测SARS-CoV-2抗体时，血清RF水平升高可能导致假阳性结果，尿素解离试验有助于降低假阳性结果的发生率。
