SARS-CoV-2 항체 검사를 위한 뉴클레오캡시드 단백질 항원을 이용한 ELISA의 분석적, 임상적 성능 평가
Evaluation of Clinical and Analytical Performance of a Nucleocapsid Protein Antigen-based ELISA for Detecting Antibodies against SARS-CoV-2
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배경: 코로나바이러스감염증-19 (코로나19)의 팬데믹이 발생하였고, 면역검사를 통한 SARS-CoV-2 (severe acute respiratory syn[1]drome coronavirus 2)에 대한 항체 검사의 필요성이 대두되었다. 방법: SARS-CoV-2의 특이 IgG, IgM, IgG/M/A total 항체를 각각 검출하는 R-FIND COVID-19 ELISA IgG, IgM, IgG/M/A (SG Medical, Inc., Korea) 3가지 종류의 시약을 개발하여 이를 평가하였다. 코로 나19 양성이 확인된 환자 87명을 대상으로 IgG 및 IgG/M/A를 평가하였고, IgM 평가에는 양성 환자 19명을 대상으로 하였다. 음성대조군으로 코로나19 음성 160명을 대상으로 하였다. 분석적 성능에 대해서는 식품의약품안전처의 체외진단 의료기기 임상적 성능시험 가이드라인에 따라 평가하였으며, 임상적 성능으로 민감도와 특이도를 평가하였다. 결과: R-FIND COVID-19 ELISA 시약의 분석적 성능은 가이드라인을 만족시켰다. 민감도와 특이도는 각각 IgG에서 94.25%와 98.13%, IgG/M/A에서 95.40%와 98.13%, IgM에서 84.21%와 100%로 나타났다. 환자 입원 후 IgM은 1주 이내 100% 양성률을 보였으며, 이후에는 감소하였다. 반면 IgG와 IgG/M/A 항체는 2주 후에 100%를 보였다. 입원 환자 연속 채혈을 통한 항체가의 변화는 입원 후 IgG와 IgG/M/A 항체가는 지속적으로 증가하였으나, IgM 역 가는 점차 감소하였다. 결론: R-FIND COVID-19 ELISA IgG, IgM, IgG/M/A 세 종류의 시약은 국내에서 개발된 제품들로 분석적 성능, 민감도와 특이도가 우수하였다. IgG의 항체가는 양성으로 유지되나 IgM의 항체가는 입원 후 지속적으로 감소하였다
Abstract
Background: As the coronavirus disease 2019 (COVID-19) pandemic evolves, the development of immunoassays that will help assess population exposure and potentially predict immunity has become a pressing priority. Methods: We evaluated the performance of the R-FIND COVID-19 enzyme-linked immunosorbent assay (ELISA) (SG Medical. Inc., Korea) for semi-quantitative detection of IgG, IgM, and IgG/M/A total antibodies in serum samples, using the SARS-CoV-2 nucleocapsid protein as antigen. Serum samples from 87 patients with COVID-19 were tested for IgG and IgG/M/A. Samples from 19 patients were tested for IgM. Specimens from 160 patients without COVID-19 served as negative controls. Analytical performance was evaluated according to Ministry of Food and Drug Safety guidelines. Sensitivity and specificity were the primary measures of clinical performance. Results: The analytical performance of the R-FIND COVID-19 ELISA met Ministry guidelines. Sensitivity and specificity were 94.25% and 98.13% for IgG, 95.40% and 98.13% for IgG/M/A, and 84.21% and 100% for IgM, respectively. IgM showed a 100% positive rate within 1 week of hospitalization, then decreased. IgG and IgG/M/A antibodies displayed 100% positivity after 2 weeks. IgG and IgG/M/A antibody titers steadily increased throughout patient hospitalization, but IgM titers gradually decreased. Conclusions: The R-FIND COVID-19 ELISA detects IgG, IgM, and IgG/M/A and displays excellent analytical performance, sensitivity, and specificity. IgG titers increased steadily throughout hospitalization, but IgM titers peaked at one week post-hospitalization, and then steadily declined
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