Review Article

Detection of Antibody versus Antigen, Optimal Option of Different Serological Assays Based Tests for COVID-19 Diagnosis: A Meta-Analysis


Background: In this study, the diagnostic efficacy of antigen test and antibody test were assessed. Additionally, the difference of sensitivity, specificity, and diagnostic odds ratio were compared concerning efficacy of antibody test versus antigen test for Corona Virus Disease 2019 (COVID-19) diagnosis.

Methods: Online databases were searched for full-text publications and STATA software was used for data pooling and analysis before Sep 1st, 2022. Forrest plot was used to show the pooled sensitivity, specificity and diagnostic odds ratio. Combined receiver operating characteristic (ROC) curve was used to show the area of under curve of complex data.

Results: Overall, 25 studies were included. The sensitivity (0.68, 95% CI: 0.53-0.80) and specificity (0.99, 95% CI: 0.98-0.99) in antibody or antigen was calculated. The time point of test lead to heterogeneity. The area under curve (AUC) was 0.98 (95% CI: 0.96-0.99), and the diagnostic odds ratio (DOR) was 299.54 (95% CI: 135.61-661.64). Subgroup analysis indicated antibody test with sensitivity (0.59, 95% CI: 0.44-0.73) and specificity (0.98, 95% CI: 0.95-0.99) and antigen test with sensitivity of 0.77 (95% CI: 0.53-0.91) and specificity of 0.99 (95% CI: 0.98-1.00). Higher AUC and DOR were proved in antigen test.

Conclusion: The present study compared the efficacy of antibody test versus antigen test for COVID-19 diagnosis. Better diagnostic efficacy, lower heterogeneity, and less publication bias of rapid antigen testing was suggested in this study. This study would help us to make better strategy about choosing rapid and reliable testing method in diagnosis of the COVID-19 disease.

1. Lisboa Bastos M, Tavaziva G, Abidi SK, et al (2020). Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ, 370:m2516.
2. Yüce M, Filiztekin E, Özkaya KG (2021). COVID-19 diagnosis -A review of current methods. Biosens Bioelectron, 172:112752.
3. Hong KH, Lee SW, Kim TS, et al (2020). Guidelines for Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19) in Korea. Ann Lab Med, 40:351-360.
4. Jin YH, Zhan QY, Peng ZY, et al (2020). Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version). Mil Med Res, 7:41.
5. Arevalo-Rodriguez I, Seron P, Buitrago-García D, et al (2021). Recommendations for SARS-CoV-2/COVID-19 testing: a scoping review of current guidance. BMJ Open, 11:e043004.
6. Dinnes J, Deeks JJ, Adriano A, et al (2020). Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. Cochrane Database Syst Rev, 8:Cd013705.
7. Carpenter CR, Mudd PA, West CP, Wilber E, Wilber ST (2020). Diagnosing COVID-19 in the Emergency Department: A Scoping Review of Clinical Examinations, Laboratory Tests, Imaging Accuracy, and Biases. Acad Emerg Med, 27:653-670.
8. Dramé M, Tabue Teguo M, Proye E, Hequet F, Hentzien M, Kanagaratnam L, Godaert L (2020). Should RT-PCR be considered a gold standard in the diagnosis of COVID-19? J Med Virol, 92:2312-2313.
9. Kanji JN, Zelyas N, MacDonald C, et al (2021). False negative rate of COVID-19 PCR testing: a discordant testing analysis. Virol J, 18:13.
10. Wölfel R, Corman VM, Guggemos W, et al (2020). Virological assessment of hospitalized patients with COVID-2019. Nature, 581:465-469.
11. Azkur AK, Akdis M, Azkur D, et al (2020). Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy, 75:1564-1581.
12. Yongchen Z, Shen H, Wang X, et al (2020). Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients. Emerg Microbes Infect, 9:833-836.
13. Miller TE, Garcia Beltran WF, Bard AZ, et al (2020). Clinical sensitivity and interpretation of PCR and serological COVID-19 diagnostics for patients presenting to the hospital. Faseb J, 34:13877-13884.
14. Waller JV, Kaur P, Tucker A, et al (2020). Diagnostic Tools for Coronavirus Disease (COVID-19): Comparing CT and RT-PCR Viral Nucleic Acid Testing. AJR Am J Roentgenol, 215:834-838.
15. Long C, Xu H, Shen Q, et l (2020). Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? Eur J Radiol, 126:108961.
16. Rai P, Kumar BK, Deekshit VK, Karunasagar I, Karunasagar I (2021). Detection technologies and recent developments in the diagnosis of COVID-19 infection. Appl Microbiol Biotechnol, 105:441-455.
17. Lai CKC, Lam W (2021). Laboratory testing for the diagnosis of COVID-19. Biochem Biophys Res Commun, 538:226-230.
18. Xie J, Ding C, Li J, et al (2020). Characteristics of patients with coronavirus disease (COVID-19) confirmed using an IgM-IgG antibody test. J Med Virol, 92:2004-2010.
19. Ejazi SA, Ghosh S, Ali N (2021). Antibody detection assays for COVID-19 diagnosis: an early overview. Immunol Cell Biol, 99:21-33.
20. Sidiq Z, Hanif M, Dwivedi KK, Chopra KK (2020). Benefits and limitations of serological assays in COVID-19 infection. Indian J Tuberc, 67:S163-s166.
21. Jiang JC, Zhang Y (2020). Serological antibody testing in the COVID-19 pandemic: their molecular basis and applications. Biochem Soc Trans, 48:2851-2863.
22. Nagura-Ikeda M, Imai K, Tabata S, et al (2020). Clinical Evaluation of Self-Collected Saliva by Quantitative Reverse Transcription-PCR (RT-qPCR), Direct RT-qPCR, Reverse Transcription-Loop-Mediated Isothermal Amplification, and a Rapid Antigen Test To Diagnose COVID-19. J Clin Microbiol, 58.
23. Albert E, Torres I, Bueno F, et al (2021). Field evaluation of a rapid antigen test (Panbio™ COVID-19 Ag Rapid Test Device) for COVID-19 diagnosis in primary healthcare centres. Clin Microbiol Infect, 27:472.e7-472.e10.
24. Scohy A, Anantharajah A, Bodéus M, Kabamba-Mukadi B, Verroken A, Rodriguez-Villalobos H (2020). Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis. J Clin Virol, 129:104455.
25. Li Z, Yi Y, Luo X, et al (2020). Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J Med Virol, 92:1518-1524.
26. Spicuzza L, Montineri A, Manuele R, et al (2020). Reliability and usefulness of a rapid IgM-IgG antibody test for the diagnosis of SARS-CoV-2 infection: A preliminary report. J Infect, 81:e53-e54.
27. Shen B, Zheng Y, Zhang X, et al (2020). Clinical evaluation of a rapid colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG. Am J Transl Res, 12:1348-1354.
28. Xiang F, Wang X, He X, et al (2020). Antibody Detection and Dynamic Characteristics in Patients With Coronavirus Disease 2019. Clin Infect Dis, 71:1930-1934.
29. Porte L, Legarraga P, Vollrath V, et al (2020). Evaluation of a novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples. Int J Infect Dis, 99:328-333.
30. Liotti FM, Menchinelli G, Lalle E, et al B (2021). Performance of a novel diagnostic assay for rapid SARS-CoV-2 antigen detection in nasopharynx samples. Clin Microbiol Infect, 27:487-488.
31. Cerutti F, Burdino E, Milia MG, Allice T, Gregori G, Bruzzone B, Ghisetti V (2020). Urgent need of rapid tests for SARS CoV-2 antigen detection: Evaluation of the SD-Biosensor antigen test for SARS-CoV-2. J Clin Virol, 132:104654-104654.
32. Linares M, Pérez-Tanoira R, Carrero A, et al (2020). Panbio antigen rapid test is reliable to diagnose SARS-CoV-2 infection in the first 7 days after the onset of symptoms. J Clin Virol, 133:104659-104659.
33. Agulló V, Fernández-González M, Ortiz de la Tabla V, Gonzalo-Jiménez N, García JA, Masiá M, Gutiérrez F (2021). Evaluation of the rapid antigen test Panbio COVID-19 in saliva and nasal swabs in a population-based point-of-care study. J Infect, 82:186-230.
34. Turcato G, Zaboli A, Pfeifer N, Ciccariello L, Sibilio S, Tezza G, Ausserhofer D (2021). Clinical application of a rapid antigen test for the detection of SARS-CoV-2 infection in symptomatic and asymptomatic patients evaluated in the emergency department: A preliminary report. J Infect, 82:e14-e16.
35. Canetti D, Dell'Acqua R, Riccardi N, et al (2020). SARS-CoV-2 IgG/IgM Rapid Test as a Diagnostic Tool in Hospitalized Patients and Healthcare Workers, at a large Teaching Hospital in northern Italy, during the 2020 COVID-19 Pandemic. New Microbiol, 43:161-165.
36. Fauziah N, Koesoemadinata RC, Andriyoko B, et al (2021). The performance of point-of-care antibody test for COVID-19 diagnosis in a tertiary hospital in Bandung, Indonesia. J Infect Dev Ctries, 15:237-241.
37. Hoffman T, Nissen K, Krambrich J, et al (2020). Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2. Infect Ecol Epidemiol, 10:1754538.
38. Döhla M, Boesecke C, Schulte B, et al (2020). Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity. Public Health, 182:170-172.
39. Alemany A, Baró B, Ouchi D, et al (2021). Analytical and clinical performance of the panbio COVID-19 antigen-detecting rapid diagnostic test. J Infect, 82:186-230.
40. Gupta A, Khurana S, Das R, et al (2021). Rapid chromatographic immunoassay-based evaluation of COVID-19: A cross-sectional, diagnostic test accuracy study & its implications for COVID-19 management in India. Indian J Med Res, 153:126-131.
41. Nalumansi A, Lutalo T, Kayiwa J, et al (2021). Field evaluation of the performance of a SARS-CoV-2 antigen rapid diagnostic test in Uganda using nasopharyngeal samples. Int J Infect Dis, 104:282-286.
42. Toptan T, Eckermann L, Pfeiffer AE, et al (2021). Evaluation of a SARS-CoV-2 rapid antigen test: Potential to help reduce community spread? J Clin Virol, 135:104713.
43. Gremmels H, Winkel BMF, Schuurman R, et al (2021). Real-life validation of the Panbio™ COVID-19 antigen rapid test (Abbott) in community-dwelling subjects with symptoms of potential SARS-CoV-2 infection. EClinicalMedicine, 31:100677.
44. Jin Y, Wang M, Zuo Z, et al (2020). Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019. Int J Infect Dis, 94:49-52.
45. Cassaniti I, Novazzi F, Giardina F, et al (2020). Performance of VivaDiag COVID-19 IgM/IgG Rapid Test is inadequate for diagnosis of COVID-19 in acute patients referring to emergency room department. J Med Virol, 92:1724-1727.
46. Chaimayo C, Kaewnaphan B, Tanlieng N, et al (2020). Rapid SARS-CoV-2 antigen detection assay in comparison with real-time RT-PCR assay for laboratory diagnosis of COVID-19 in Thailand. Virol J, 17:177.
47. Akashi Y, Horie M, Takeuchi Y, et al (2022). A prospective clinical evaluation of the diagnostic accuracy of the SARS-CoV-2 rapid antigen test using anterior nasal samples. J Infect Chemother, 28:780-785.
48. Roda A, Cavalera S, Di Nardo F, et al (2021). Dual lateral flow optical/chemiluminescence immunosensors for the rapid detection of salivary and serum IgA in patients with COVID-19 disease. Biosens Bioelectron, 172:112765.
49. Torres I, Poujois S, Albert E, Colomina J, Navarro D (2021). Evaluation of a rapid antigen test (Panbio™ COVID-19 Ag rapid test device) for SARS-CoV-2 detection in asymptomatic close contacts of COVID-19 patients. Clin Microbiol Infect, 27:636.e1-636.e4.
50. Andrey DO, Cohen P, Meyer B, et al (2020). Diagnostic accuracy of Augurix COVID-19 IgG serology rapid test. Eur J Clin Invest, 50:e13357.
IssueVol 52 No 1 (2023) QRcode
SectionReview Article(s)
SARS-CoV-2 COVID-19 Antibody test Antigen test Meta-analysis

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Fu H, Sun L, Zhu J. Detection of Antibody versus Antigen, Optimal Option of Different Serological Assays Based Tests for COVID-19 Diagnosis: A Meta-Analysis. Iran J Public Health. 2023;52(1):23-36.