Document Type : Original Research


1 Department of Pathology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Infectious Diseases and Tropical Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 Radiation Oncology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Cardiology, Tehran University of Medical Sciences, Tehran, Iran


Background & Objective: COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) has been a reference test for diagnosing a disease since the very beginning of the pandemic. COVID-19 serology tests have also been developed and used to estimate the prevalence of individuals who have already been infected. We aimed to evaluate the performance of serology tests for the diagnosis of patients who had been referred to medical centers with acute symptoms.
Methods: In this cross-sectional study, 80 individuals suspected of COVID-19 who had been referred to Imam Khomeini Hospital Complex, Tehran, Iran, were examined. Upper respiratory tract specimens for RT-PCR and blood samples for COVID-19 IgM and IgG antibody level tests were collected and the results were compared.  
Results: The overall proportion in agreement, the agreement between positive results, and the agreement between negative results when comparing RT-PCR and IgM serology test were 40% (kappa = -0.006, P = 0.9), 32%, and 66.6%, respectively, and when comparing RT-PCR and IgG serology test were 46% (kappa = -0.006, P = 0.94), 43.5%, and 55.5%, respectively.
Conclusion: The absence of a gold standard method for the diagnosis of COVID-19 makes it very challenging to determine the true sensitivity and specificity of different methods. The study results revealed no agreement between the two methods; so the RT-PCR test for upper respiratory tract specimen cannot be replaced with COVID-19 serology test for the diagnosis of patients with acute symptoms.


Main Subjects

1. Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol. 2020;92(4):441-7. [DOI:10.1002/jmv.25689] [PMID] [PMCID]
2. Tang YW, Schmitz JE, Persing DH, Stratton CW. Laboratory Diagnosis of COVID-19: Current Issues and Challenges. J Clin Microbiol. 2020;58(6):e00512-20. [DOI:10.1128/JCM.00512-20]
3. Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clin Infect Dis. 2020:ciaa270. [DOI:10.1093/cid/ciaa270] [PMID] [PMCID]
4. Beeching NJ, Fletcher TE, Beadsworth MBJ. Covid-19: testing times. BMJ. 2020;369:m1403. [DOI:10.1136/bmj.m1403] [PMID]
5. Watson J, Whiting PF, Brush JE. Interpreting a covid-19 test result. BMJ. 2020;369:m1808. [DOI:10.1136/bmj.m1808] [PMID]
6. Wang X, Tan L, Wang X, Liu W, Lu Y, Cheng L, et al. Comparison of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 detection in 353 patients received tests with both specimens simultaneously. Int J Infect Dis. 2020;94:107-9. [DOI:10.1016/j.ijid.2020.04.023] [PMID] [PMCID]
7. Woloshin S, Patel N, Kesselheim AS. False Negative Tests for SARS-CoV-2 Infection - Challenges and Implications. N Engl J Med. 2020;383(6):e38. [DOI:10.1056/NEJMp2015897] [PMID]
8. Drame M, Tabue Teguo M, Proye E, Hequet F, Hentzien M, Kanagaratnam L, et al. Should RT-PCR be considered a gold standard in the diagnosis of COVID-19? J Med Virol. 2020;92(11):2312-3. [DOI:10.1002/jmv.25996] [PMID] [PMCID]
9. U.S. Food and Drug Administration. Guidance for industry and FDA staff. Statistical guidance on reporting results from studies evaluating diagnostic tests. March 13, 2007 [Available from:
10. Guideline for the diagnosis and treatment of COVID-19 in outpatients and inpatients. Health and Treatment Deputy of the Ministry of Health and Medical Education. 2020 [Available from:
11. Spicuzza L, Montineri A, Manuele R, Crimi C, Pistorio MP, Campisi R, et al. Reliability and usefulness of a rapid IgM-IgG antibody test for the diagnosis of SARS-CoV-2 infection: A preliminary report. J Infect. 2020;81(2):e53-e4. [DOI:10.1016/j.jinf.2020.04.022] [PMID] [PMCID]
12. To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020;20(5):565-74. [DOI:10.1016/S1473-3099(20)30196-1]
13. Pfluger LS, Bannasch JH, Brehm TT, Pfefferle S, Hoffmann A, Norz D, et al. Clinical evaluation of five different automated SARS-CoV-2 serology assays in a cohort of hospitalized COVID-19 patients. J Clin Virol. 2020;130:104549. [DOI:10.1016/j.jcv.2020.104549] [PMID] [PMCID]
14. Oliveira BA, Oliveira LC, Sabino EC, Okay TS. SARS-CoV-2 and the COVID-19 disease: a mini review on diagnostic methods. Rev Inst Med Trop Sao Paulo. 2020;62:e44. [DOI:10.1590/s1678-9946202062044] [PMID] [PMCID]
15. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody Responses to SARS-CoV-2 in Patients With Novel Coronavirus Disease 2019. Clin Infect Dis. 2020;71(16):2027-34. [DOI:10.1093/cid/ciaa344] [PMID] [PMCID]
16. Tre-Hardy M, Blairon L, Wilmet A, Beukinga I, Malonne H, Dogne JM, et al. The role of serology for COVID-19 control: Population, kinetics and test performance do matter. J Infect. 2020;81(2):e91-e2. [DOI:10.1016/j.jinf.2020.05.019] [PMID] [PMCID]
17. Mallett S, Allen AJ, Graziadio S, Taylor SA, Sakai NS, Green K, et al. At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data. BMC Med. 2020;18(1):346. [DOI:10.1186/s12916-020-01810-8] [PMID] [PMCID]
18. Lerner AM, Eisinger RW, Lowy DR, Petersen LR, Humes R, Hepburn M, et al. The COVID-19 Serology Studies Workshop: Recommendations and Challenges. Immunity. 2020;53(1):1-5. [DOI:10.1016/j.immuni.2020.06.012] [PMID] [PMCID]
19. Lisboa Bastos M, Tavaziva G, Abidi SK, Campbell JR, Haraoui LP, Johnston JC, et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ. 2020;370:m2516. [DOI:10.1136/bmj.m2516] [PMID] [PMCID]
20. Miller TE, Garcia Beltran WF, Bard AZ, Gogakos T, Anahtar MN, Astudillo MG, et al. Clinical sensitivity and interpretation of PCR and serological COVID-19 diagnostics for patients presenting to the hospital. FASEB J. 2020;34(10):13877-84. [DOI:10.1096/fj.202001700RR] [PMID] [PMCID]