新型冠状病毒抗原胶体金免疫层析检测试剂的国际多中心临床评价

International multi‑center evaluation of a rapid antigen test based on gold immunochromatographic assay for detection of severe acute respiratory syndrome coronavirus 2

目的对新型冠状病毒(SARS‑CoV‑2)抗原检测试剂盒(胶体金免疫层析法)进行国际多中心临床评价。方法1855份具有有效检测结果的临床平行样本(分别用于核酸和抗原检测)来自德国、英国、乌克兰、法国、印度、泰国、马来西亚、美国和巴西9个国家,采样时间为2021年1月3日至9月22日。对这些样本分别采用SARS‑CoV‑2抗原检测试剂盒(胶体金免疫层析法)和核酸检测试剂盒(RT‑PCR)进行检测,计算阳性符合率[(抗原阳性例数/核酸阳性例数)×100%]、阴性符合率[(抗原阴性例数/核酸阴性例数)×100%]、总符合率[(抗原和核酸检测一致的例数/总例数)×100%]和Kappa值。采用变异系数评价以上指标在不同国家间的差异。分析不同核酸检测循环阈值(Ct值)样本、不同特征样本和不同突变株样本的抗原检出率。结果所有样本SARS‑CoV‑2抗原检测与核酸检测阳性符合率为90.8%(569/627),阴性符合率为99.7%(1224/1228),总符合率为96.7%(1793/1855),一致性系数Kappa值为0.924;各国间的阳性符合率(除含Ct值>30样本较多的马来西亚外)、阴性符合率(除不含阴性样本的法国外)和总符合率(除法国外)的变异系数分别为6%、<1%和6%。当Ct值<25时抗原检出率可达83.3%~100%(变异系数为6%),无症状感染者和症状出现7 d内样本总体检出率和变异系数分别为93.4%(428/458)和5%,对SARS‑CoV‑2突变株的总检出率为97.5%(119/122),对20份其他病毒感染样本(包括甲型流感病毒H1N1、乙型流感病毒、呼吸道合胞病毒A型和B型、肠道萨奇病毒A组16、人类偏肺病毒、副流感病毒1型和4型、EB病毒和腺病毒)的抗原检测结果均为阴性。结论SARS‑CoV‑2抗原检测试剂盒检测真实性好,且其各指标在9个国家间差异较小,可满足大规模早期筛查SARS‑CoV‑2感染的需要。

Objective The gold immunochromatographic assay for detection of SARS‑CoV‑2 antigen was evaluated by international multi‑center clinical trial.Methods A total of 1855 clinical parallel samples with valid test results(for nucleic acid and antigen tests,respectively)were collected from nine countries,including Germany,the United Kingdom,Ukraine,France,India,Thailand,Malaysia,the United States of America and Brazil,with sampling period from January 3 to September 22,2021.These samples were detected by SARS‑CoV‑2 antigen test kit(colloidal gold immunochromatography assay)and nucleic acid detection kit(real‑time fluorescent quantitative reverse transcription polymerase chain reaction).Positive coincidence rates[(number of antigen‑positive cases/nucleic acid‑positive cases)×100%],negative coincidence rates[(number of antigen‑negative cases/nucleic acid‑negative cases)×100%],total coincidence rates[(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases)×100%],as well as Kappa values were calculated.The differences of the above indictors among different countries were evaluated by the coefficient of variation.The detection rates of the antigen test for samples with different cycle threshold values(Ct values)for the nucleic acid detection,different characteristics and different mutant strains were analyzed.Results For all samples,the positive,negative,and total coincidence rate between the antigen test and nucleic acid assay was 90.8%(569/627),99.7%(1224/1228)and 96.7%(1793/1855),respectively,and the consistency coefficient Kappa value was 0.924.Among these countries,the coefficient of variation for positive coincidence rates(except for Malaysia with a lot of samples with Ct value>30),negative coincidence rates(except for France without negative samples)and total coincidence rates(except for France)was 6%,<1%,and 6%,respectively.When Ct values were less than 25,the detection rates of antigen test were 83.3%‑100%for each countries(the coefficient of variation was 6%);the total detection rate and the coefficient of variation was 93.4%(428/458)and 5%,respectively,for asymptomatic infected persons and cases within 7 days post onset of symptoms;the total detection rate for various SARS‑CoV‑2 mutant strains was 97.5%(119/122);and it showed negative results for samples from cases infected with other viruses,including influenza A virus subtype H1N1,influenza B virus,respiratory syncytial virus subgroups A and B,coxsackievirus 16,human metapneumovirus,parainfluenza virus types 1 and 4,Epstein‑Barr virus and adenovirus.Conclusion The SARS‑CoV‑2 antigen test kit showed excellent authenticity,and there were few differences for its indictors among nine countries,therefore it can meet the needs of large‑scale early screening of SARS‑CoV‑2 infection.