Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis

Zhengtu Li, Yongxiang Yi, Xiaomei Luo, Nian Xiong, Yang Liu, Shaoqiang Li, Ruilin Sun, Yanqun Wang, Bicheng Hu, Wei Chen, Yongchen Zhang, Jing Wang, Baofu Huang, Ye Lin, Jiasheng Yang, Wensheng Cai, Xuefeng Wang, Jing Cheng, Zhiqiang Chen, Kangjun Sun, Weimin Pan, Zhifei Zhan, Liyan Chen, Feng Ye, Zhengtu Li, Yongxiang Yi, Xiaomei Luo, Nian Xiong, Yang Liu, Shaoqiang Li, Ruilin Sun, Yanqun Wang, Bicheng Hu, Wei Chen, Yongchen Zhang, Jing Wang, Baofu Huang, Ye Lin, Jiasheng Yang, Wensheng Cai, Xuefeng Wang, Jing Cheng, Zhiqiang Chen, Kangjun Sun, Weimin Pan, Zhifei Zhan, Liyan Chen, Feng Ye

Abstract

The outbreak of the novel coronavirus disease (COVID-19) quickly spread all over China and to more than 20 other countries. Although the virus (severe acute respiratory syndrome coronavirus [SARS-Cov-2]) nucleic acid real-time polymerase chain reaction (PCR) test has become the standard method for diagnosis of SARS-CoV-2 infection, these real-time PCR test kits have many limitations. In addition, high false-negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify a large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point-of-care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS-CoV-2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID-19 patients and 128 negative patients at eight different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.

Keywords: COVID-19; SARS-CoV-2 virus infection; fingerstick blood; lateral flow immunoassay; point-of-care testing; rapid IgM-IgG combined test.

Conflict of interest statement

The authors declare that there are no conflict of interests.

© 2020 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Schematic illustration of rapid SARS‐CoV‐2 IgM‐IgG combined antibody test. A, Schematic diagram of the detection device; B, an illustration of different testing results; C, means control line; G, means IgG line; M, means IgM line. IgG, immunoglobulin G; IgM, immunoglobulin M; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2
Figure 2
Figure 2
Representative photo for different patient blood testing results. (#13) Both IgM and IgG positive, (#14) IgM weak positive, (#15) Both IgM and IgG negative, (#16) IgG weak positive, (#17) IgG positive, and (#18) IgM positive. IgG, immunoglobulin G; IgM, immunoglobulin M

References

    1. WHO . Novel coronavirus—China. . Accessed January 12, 2020.
    1. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727‐733.
    1. Ksiazek TG, Erdman D, Goldsmith CS, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1953‐1966.
    1. Kuiken T, Fouchier RA, Schutten M, et al. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet. 2003;362(9380):263‐270.
    1. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19):1814‐1820.
    1. Centers for Disease Control and Prevention CfDCaP . Confirmed COVID‐19 Cases Globally. . Accessed February 15, 2020.
    1. Prevention CCfDCa . Distribution of pneumonic outbreaks of COVID‐19 infection. . Accessed February 19, 2020.
    1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497‐506.
    1. Wang C, Yu H, Horby PW, et al. Comparison of patients hospitalized with influenza A subtypes H7N9, H5N1, and 2009 pandemic H1N1. Clin Infect Dis. 2014;58(8):1095‐1103.
    1. Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (COVID‐19) infected pneumonia (standard version). Mil Med Res. 2020;7(1):4.
    1. Gallagher J. Are coronavirus tests flawed? BBC News . . Accessed 13 February, 2020.
    1. Racine R, Winslow GM. IgM in microbial infections: taken for granted? Immunol Lett. 2009;125(2):79‐85.
    1. Lee HK, Lee BH, Seok SH, et al. Production of specific antibodies against SARS‐coronavirus nucleocapsid protein without cross reactivity with human coronaviruses 229E and OC43. J Vet Sci. 2010;11(2):165‐167.
    1. Wan ZY, Zhang X, Yan XG. IFA in testing specific antibody of SARS coronavirus. South China J Prev Med. 2003;29(3):36‐37.
    1. Prevention CCfDCa . The guideline of diagnosis and treatment of COVID‐19. . Accessed February 9, 2020.
    1. Singer AJ, Williams J, Taylor M, Le Blanc D, Thode HC Jr. Comprehensive bedside point of care testing in critical ED patients: a before and after study. Am J Emerg Med. 2015;33(6):776‐780.
    1. Rothe C, Schunk M, Sothmann P, et al. Transmission of COVID‐19 Infection from an asymptomatic contact in Germany. N Engl J Med. 2020;382(10):970‐971.
    1. Zou L, Ruan F, Huang M, et al. SARS‐CoV‐2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020:NEJMc2001737.
    1. Turner LH, Kinder JM, Wilburn A, et al. Preconceptual Zika virus asymptomatic infection protects against secondary prenatal infection. PLOS Pathog. 2017;13(11):e1006684.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera