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Diagnostic Accuracy of COVID-19 Antibody Tests Authorized by FDA Philippines: A Systematic Review and Meta-Analysis

Carmel Reina R. Chua, Esther Delle E. de los Santos, Karla Veronica H. Escasa, Richmond Louis G. Estolas, Junnealyn Feliciano, Sabrina Audrey E. Ortega, Carlo Ledesma, Jan Ebrian D. Leonin, Sherill D. Tesalona

Abstract


Introduction: Coronavirus Disease (COVID-19) is a highly infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which has infected many people all over the world. One of the best ways to lessen its spread is through early detection and diagnosis. Various serological tests are now being used as a surveillance tool in the detection of antibodies as a response to SARS-CoV-2. The aim of this study is to evaluate the diagnostic accuracy and performance of the available COVID-19 antibody tests authorized by the Food and Drug Administration (FDA) Philippines that make use of Enzyme-Linked Immunosorbent Assay (ELISA), Chemiluminescence Immunoassay (CLIA) and Lateral Flow Immunoassay (LFIA). Method: Complete published journal articles relevant to the diagnostic accuracy of the three antibody tests were collected using trusted medical journal search engines. The quality of journals was assessed using QUADAS-2 to determine the risk of bias and assess the applicability judgments of diagnostic accuracy studies. Forest plots were used to summarize the performance of LFIA, ELISA and CLIA according to their specificity and sensitivity in detecting various antibodies. Pooled sensitivity and specificity were also done using bivariate random-effects models with its log-likelihood, a corresponding chi-square test statistic, and area under the summary Receiver-Operating Characteristic curve to see the potential heterogeneity in the data and to assess the diagnostic accuracy of the COVID-19 antibody tests. Results: Bivariate random-effects model and areas under the sROC curve were used to evaluate the diagnostic accuracy of COVID-19 antibody tests. The pooled sensitivity in detecting IgG based on CLIA, ELISA, and LFIA were 81.7%, 58.7%, and 74.3% respectively, with an overall of 72.0%. For IgM detection, LFIA has a higher pooled sensitivity of 69.6% than CLIA with 61.0%. Overall, the pooled sensitivity is 68.5%. In IgA detection, only ELISA based test was included with a pooled sensitivity of 84.8%. Lastly, pooled sensitivities for combined antibodies based on ELISA and LFIA were 89.0% and 81.6% respectively, with an overall of 82.5%. On the other hand, all tests excluding ELISA-IgA displayed high pooled specificities with a range of 94.0% to 100.0%. Diagnostic accuracies of the test in detecting IgG, IgM, and combined antibodies were found out to be almost perfect based on the computed area under the sROC with values of 0.973, 0.953, and 0.966, respectively. Conclusion: In this systematic review and meta-analysis, existing evidence on the diagnostic accuracy of antibody tests for COVID-19 were found to be characterized by high risks of bias, consistency in the heterogeneity of sensitivities, and consistency in the homogeneity of high specificities except in IgA detection using ELISA. The bivariate random-effects models showed that there are no significant differences in terms of sensitivity among CLIA, ELISA and LFIA in detecting IgG, IgM, and combined antibodies at a 95% confidence interval. Nonetheless, CLIA, ELISA and LFIA were found to have excellent diagnostic accuracies in the detection of IgG, IgM and combined antibodies as reflected by their AUC values.

 

Doi: 10.28991/SciMedJ-2021-0304-1

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Keywords


COVID-19; Antibody Test; Enzyme-linked Immunosorbent Assay (ELISA); Chemiluminescence Immunoassay (CLIA); Lateral Flow Immunoassay (LFIA).

References


Worldometers website, Philippines COVID: 101,400,862 cases and 2,182,193 Deaths-Worldometer. (2020). Worldometers.info. Available online: https://www.worldometers.info/coronavirus/country/philippines/ (accessed on May 2021).

Feng, W., Newbigging, A. M., Le, C., Pang, B., Peng, H., Cao, Y., Wu, J., Abbas, G., Song, J., Wang, D. B., Cui, M., Tao, J., Tyrrell, D. L., Zhang, X. E., Zhang, H., & Le, X. C. (2020). Molecular Diagnosis of COVID-19: Challenges and Research Needs. Analytical chemistry, 92(15), 10196–10209. doi:10.1021/acs.analchem.0c02060.

Udugama, B., Kadhiresan, P., Kozlowski, H. N., Malekjahani, A., Osborne, M., Li, V., Chen, H., Mubareka, S., Gubbay, J. B., & Chan, W. (2020). Diagnosing COVID-19: The Disease and Tools for Detection. ACS nano, 14(4), 3822–3835. doi:10.1021/acsnano.0c02624.

Batra, R., Olivieri, L. G., Rubin, D., Vallari, A., Pearce, S., Olivo, A., Prostko, J., Nebbia, G., Douthwaite, S., Rodgers, M., & Cloherty, G. (2020). A comparative evaluation between the Abbott PanbioTM COVID-19 IgG/IgM rapid test device and Abbott ArchitectTM SARS CoV-2 IgG assay. Journal of Clinical Virology, 132, 104645. doi:10.1016/j.jcv.2020.104645.

Catry, E., Jacqmin, H., Dodemont, M., Saad Albichr, I., Lardinois, B., de fays, B., Delaere, B., Closset, M., Laurent, T., Denis, O., Galanti, L., Mullier, F., & Huang, T. D. (2021). Analytical and clinical evaluation of four commercial SARS-CoV-2 serological immunoassays in hospitalized patients and ambulatory individuals. Journal of Virological Methods, 289(August 2020), 114060. doi:10.1016/j.jviromet.2020.114060.

Charlton, C. L., Kanji, J. N., Johal, K., Bailey, A., Plitt, S. S., MacDonald, C., Kunst, A., Buss, E., Burnes, L. E., Fonseca, K., Berenger, B. M., Schnabl, K., Hu, J., Stokes, W., Zelyas, N., & Tipples, G. (2020). Evaluation of six commercial mid- To high-volume antibody and six point-of-care lateral flow assays for detection of SARS-CoV-2 antibodies. Journal of Clinical Microbiology, 58(10), 1–12. doi:10.1128/JCM.01361-20.

Choe, J. Y., Kim, J. W., Kwon, H. H., Hong, H. L., Jung, C. Y., Jeon, C. H., Park, E. J., & Kim, S. K. (2020). Diagnostic performance of immunochromatography assay for rapid detection of IgM and IgG in coronavirus disease 2019. Journal of Medical Virology, 92(11), 2567–2572. doi:10.1002/jmv.26060.

Gutiérrez-Cobos, A., Gómez de Frutos, S., Domingo García, D., Navarro Lara, E., Yarci Carrión, A., Fontán García-Rodrigo, L., Fraile Torres, A. M., & Cardeñoso Domingo, L. (2020). Evaluation of diagnostic accuracy of 10 serological assays for detection of SARS-CoV-2 antibodies. European Journal of Clinical Microbiology and Infectious Diseases. doi:10.1007/s10096-020-04092-3.

Cota, G., Freire, M. L., de Souza, C. S., Pedras, M. J., Saliba, J. W., Faria, V., Alves, L. L., Rabello, A., & Avelar, D. M. (2020). Diagnostic performance of commercially available COVID-19 serology tests in Brazil. International Journal of Infectious Diseases, 101, 382–390. doi:10.1016/j.ijid.2020.10.008.

Daoud, Z., McLeod, J., & Stockman, D. L. (2020). Higher Sensitivity Provided by the Combination of Two Lateral Flow Immunoassay Tests for the Detection of COVID-19 Immunoglobulins. Frontiers in Cellular and Infection Microbiology, 10(October), 1–14. doi:10.3389/fcimb.2020.00479.

Dortet, L., Ronat, J. B., Vauloup-Fellous, C., Langendorf, C., Mendels, D. A., Emeraud, C., … Naas, T. (2021). Evaluating 10 commercially available SARS-CoV-2 rapid serological tests by use of the STARD (standards for reporting of diagnostic accuracy studies) method. Journal of Clinical Microbiology, 59(2), 1–12. doi:10.1128/JCM.02342-20.

Dou, X., Wang, E., Hu, J., Zong, Z., Jiang, R., Wang, M., Kan, L., & Zhang, X. (2021). Comparison of three automatic chemiluminescent immunoassays for monitoring dynamic profile of SARS-CoV-2 IgG and IgM. Journal of Clinical Laboratory Analysis, 35(1), 1–10. doi:10.1002/jcla.23681.

Hackner, K., Errhalt, P., Willheim, M., Schragel, F., Grasl, M.-A., Lagumdzija, J., … Assadian, O. (2020). Diagnostic accuracy of two commercially available rapid assays for detection of IgG and IgM antibodies to SARS-CoV-2 compared to ELISA in a low-prevalence population. GMS Hygiene and Infection Control, 15, Doc28. doi:10.3205/dgkh000363.

Kittel, M., Muth, M. C., Zahn, I., Roth, H. J., Thiaucourt, M., Gerhards, C., Haselmann, V., Neumaier, M., & Findeisen, P. (2021). Clinical evaluation of commercial automated SARS-CoV-2 immunoassays. International Journal of Infectious Diseases, 103, 590–596. doi:10.1016/j.ijid.2020.12.003.

McAulay, K., Bryan, A., Greninger, A. L., Grill, F., Lake, D., Kaleta, E. J., & Grys, T. E. (2020). Retrospective clinical evaluation of 4 lateral flow assays for the detection of SARS-CoV-2 IgG. Diagnostic Microbiology and Infectious Disease, 98(3), 115161. doi:10.1016/j.diagmicrobio.2020.115161.

Montesinos, I., Gruson, D., Kabamba, B., Dahma, H., Van den Wijngaert, S., Reza, S., Carbone, V., Vandenberg, O., Gulbis, B., Wolff, F., & Rodriguez-Villalobos, H. (2020). Evaluation of two automated and three rapid lateral flow immunoassays for the detection of anti-SARS-CoV-2 antibodies. Journal of Clinical Virology, 128(April), 104413. doi:10.1016/j.jcv.2020.104413.

Nilsson, A. C., Holm, D. K., Justesen, U. S., Gorm-Jensen, T., Andersen, N. S., Øvrehus, A., … Lillevang, S. T. (2021). Comparison of six commercially available SARS-CoV-2 antibody assays—Choice of assay depends on intended use. International Journal of Infectious Diseases, 103, 381–388. doi:10.1016/j.ijid.2020.12.017.

Pallett, S. J. C., Rayment, M., Patel, A., Fitzgerald-smith, S. A. M., Denny, S. J., Charani, E., Mai, A. L., Gilmour, K. C., Hatcher, J., Scott, C., Randell, P., Mughal, N., Jones, R., Moore, L. S. P., & Davies, G. W. (2020). Articles Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK : a prospective multicentre cohort study. The Lancet Respiratory, 2600(20), 1–10. doi:10.1016/S2213-2600(20)30315-5.

Tan, S. S., Saw, S., Chew, K. L., Huak, C. Y., Khoo, C., Pajarillaga, A., … Sethi, S. K. (2020). Head-to-head evaluation on diagnostic accuracies of six SARS-CoV-2 serological assays. Pathology, 52(7), 770–777. doi:10.1016/j.pathol.2020.09.007.

Li, T., Wang, L., Wang, H., Li, X., Zhang, S., Xu, Y., & Wei, W. (2020). Serum SARS-COV-2 Nucleocapsid Protein: A Sensitivity and Specificity Early Diagnostic Marker for SARS-COV-2 Infection. Frontiers in Cellular and Infection Microbiology, 10(September), 1–8. doi:10.3389/fcimb.2020.00470.

Wakita, M., Idei, M., Saito, K., Horiuchi, Y., Yamatani, K., Ishikawa, S., … Tabe, Y. (2021). Comparison of the clinical performance and usefulness of five SARS-CoV-2 antibody tests. PLoS ONE, 16(2 February), 1–10. doi:10.1371/journal.pone.0246536.

Xie, X., Nielsen, M. C., Muruato, A. E., Fontes-Garfias, C. R., & Ren, P. (2021). Evaluation of a SARS-CoV-2 lateral flow assay using the plaque reduction neutralization test. Diagnostic Microbiology and Infectious Disease, 99(2). doi:10.1016/j.diagmicrobio.2020.115248.

Mandrekar, J. N. (2010). Receiver operating characteristic curve in diagnostic test assessment. Journal of Thoracic Oncology, 5(9), 1315–1316. doi:10.1097/JTO.0b013e3181ec173d.

Kim, K. W., Lee, J., Choi, S. H., Huh, J., & Park, S. H. (2015). Systematic Review and Meta-Analysis of Studies Evaluating Diagnostic Test Accuracy: A Practical Review for Clinical Researchers-Part I. General Guidance and Tips. Korean Journal of Radiology, 16(6), 1175. doi:10.3348/kjr.2015.16.6.1175.


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DOI: 10.28991/SciMedJ-2021-0304-1

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Copyright (c) 2021 Carmel Reina Ruano Chua, Esther Delle Esguerra de los Santos, Karla Veronica Hernando Escasa, Richmond Louis Gulapa Estolas, Junnealyn Feliciano, Sabrina Audrey Esteban Ortega, Sherill Delos Reyes Tesalona, Carlo Ledesma