Document Type : Review article


1 Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

2 Epidemiologist, Social Determinants of Health Research Center, Urmia University of Medical Sciences, Urmia, Iran

3 School of Nursing, Gerash University of Medical Sciences, Gerash, Iran

4 Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran

5 Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

6 Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

7 Department of Genetics and Immunology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran


Background and aims: In late December 2019, a cluster of progressive pneumonia-like respiratory syndromes broke out in Wuhan, China. As the number of cases continued to rise, the 2019 coronavirus disease (COVID-19) has been declared a global public health emergency. The causative agent, i.e., SARS-CoV-2, is a highly contagious strain, which has resulted in the rapid worldwide outbreak of COVID-19. COVID-19 is an overwhelmingly transmissible disease that requires early and accurate diagnosis for proper and timely treatment of suspected cases.
Materials and Methods: In order to access the scientific documentation and evidence related to the subject published during 2019 to 2021, English keywords including “COVID-19”, “SARS-CoV-2”, “Diagnosis”, “Immunoglobulin G (IgG)”, “Immunoglobulin M (IgM)”, and ‘Polymerase Chain Reaction (PCR)” were searched in Medline, PubMed, and Google Scholar databases and Persian versions of these keywords were also looked for in Jihad-e Daneshgahi’s Scientific Information Database (SID) and Iranian Journals database (Magiran)
Results: With respect to diagnosis, serum antibody assays, nucleic acid sequencing, and radiologic evaluation are among the most reliable methods to rule out the disease in suspicious cases. This review is a synopsis of the pathogenesis of coronavirus, which will mainly focus on the diagnostic methods, as well as laboratory changes in immunoglobulins, polymerase chain reaction results, and computed tomography (CT) findings.
Conclusion: Early diagnosis matters in that it not only contributes to the prevention of further transmission of the virus by asymptomatic carriers but also paves the way for clinicians to accurately choose the best therapeutic approach depending on the status of the patients.


1. Hassan SA, Sheikh FN, Jamal S, Ezeh JK, Akhtar A. Coronavirus (COVID-19): a review of clinical features, diagnosis, and treatment. Cureus. 2020;12(3):e7355. doi: 10.7759/cureus.7355. 
2. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-74. doi: 10.1016/ s0140-6736(20)30251-8. 
3. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez- Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera- Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis. 2020;34:101623. doi: 10.1016/j. tmaid.2020.101623. 
4. Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020;92(4):418-23. doi: 10.1002/jmv.25681. 
5. Sheervalilou R, Shirvaliloo M, Dadashzadeh N, Shirvalilou S, Shahraki O, Pilehvar-Soltanahmadi Y, et al. COVID-19 under spotlight: a close look at the origin, transmission, diagnosis, and treatment of the 2019-nCoV disease. J Cell Physiol. 2020;235(12):8873-924. doi: 10.1002/jcp.29735. 
6. Wang Y, Kang H, Liu X, Tong Z. Combination of RT-qPCR testing and clinical features for diagnosis of COVID-19 facilitates management of SARS-CoV-2 outbreak. J Med Virol. 2020;92(6):538-9. doi: 10.1002/jmv.25721. 
7. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. doi: 10.1016/s0140-6736(20)30211-7. 
8. Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2020. 
9. Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol. 2020;92(6):568-76. doi: 10.1002/jmv.25748. 
10. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. 2020;172(9):577-82. doi: 10.7326/m20-0504. 
11. Jia X, Zhang P, Tian Y, Wang J, Zeng H, Wang J, et al. Clinical significance of an IgM and IgG test for diagnosis of highly suspected COVID-19. Front Med (Lausanne). 2021;8:569266. doi: 10.3389/fmed.2021.569266. 
12. Mawaddah A, Gendeh HS, Lum SG, Marina MB. Upper respiratory tract sampling in COVID-19. Malays J Pathol. 2020;42(1):23-35. 
13. Shoenfeld Y. Corona (COVID-19) time musings: our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning. Autoimmun Rev. 2020;19(6):102538. doi: 10.1016/j.autrev.2020.102538. 
14. Al-Tawfiq JA, Memish ZA. Diagnosis of SARS-CoV-2 infection based on CT scan vs RT-PCR: reflecting on experience from MERS-CoV. J Hosp Infect. 2020;105(2):154- 5. doi: 10.1016/j.jhin.2020.03.001. 
15. Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, et al. Correlation of chest CT and RT-PCR testing for coronavirus disease 2019 
(COVID-19) in China: a report of 1014 cases. Radiology. 2020;296(2):E32-E40. doi: 10.1148/radiol.2020200642. 
16. Jin C, Chen W, Cao Y, Xu Z, Tan Z, Zhang X, et al. Development and evaluation of an artificial intelligence system for COVID-19 diagnosis. Nat Commun. 2020;11(1):5088. doi: 10.1038/s41467-020-18685-1. 
17. Berhe B, Legese H, Degefa H, Adhanom G, Gebrewahd A, Mardu F, et al. Global epidemiology, pathogenesis, immune response, diagnosis, treatment, economic and psychological impact, challenges, and future prevention of COVID-19: a scoping review. medRxiv. 2020. doi: 10.1101/2020.04.02.20051052. 
18. Chu DKW, Pan Y, Cheng SMS, Hui KPY, Krishnan P, Liu Y, et al. Molecular diagnosis of a novel coronavirus (2019- nCoV) causing an outbreak of pneumonia. Clin Chem. 2020;66(4):549-55. doi: 10.1093/clinchem/hvaa029. 
19. Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020;20(4):425-34. doi: 10.1016/s1473- 3099(20)30086-4. 
20. Ma C, Gu J, Hou P, Zhang L, Bai Y, Guo Z, et al. Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis. medRxiv. 2020. doi: 10.1101/2020.03.17.20037572. 
21. Rando HM, Greene CS, Robson MP, Boca SM, Wellhausen N, Lordan R, et al. SARS-CoV-2 and COVID-19: An Evolving Review of Diagnostics and Therapeutics. Manubot; 2020. 
22. Zhang P, Gao Q, Wang T, Ke Y, Mo F, Jia R, et al. Evaluation of recombinant nucleocapsid and spike proteins for serological diagnosis of novel coronavirus disease 2019 (COVID-19). medRxiv. 2020. doi: 10.1101/2020.03.17.20036954. 
23. Lin D, Liu L, Zhang M, Hu Y, Yang Q, Guo J, et al. Evaluations of the serological test in the diagnosis of 2019 novel coronavirus (SARS-CoV-2) infections during the COVID-19 outbreak. Eur J Clin Microbiol Infect Dis. 2020;39(12):2271-7. doi: 10.1007/s10096-020-03978-6. 
24. Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2):102-8. doi: 10.1016/j.jpha.2020.03.001. 
25. Han G, Sinjab A, Treekitkarnmongkol W, Brennan P, Hara K, Chang K, et al. Single-cell analysis of human lung epithelia reveals concomitant expression of the SARS-CoV-2 receptor ACE2 with multiple virus receptors and scavengers in alveolar type II cells. bioRxiv. 2020. doi: 10.1101/2020.04.16.045617. 
26. Jamil S, Mark N, Carlos G, Dela Cruz CS, Gross JE, Pasnick S. Diagnosis and management of COVID-19 disease. Am J Respir Crit Care Med. 2020;201(10):P19-P20. doi: 10.1164/ rccm.2020C1 . 
27. Gao L, Zhang J. Pulmonary high-resolution computed tomography (HRCT) findings of patients with early-stage coronavirus disease 2019 (COVID-19) in Hangzhou, China. Med Sci Monit. 2020;26:e923885. doi: 10.12659/ msm.923885. 
28. Han C, Duan C, Zhang S, Spiegel B, Shi H, Wang W, et al. Digestive symptoms in COVID-19 patients with mild disease severity: clinical presentation, stool viral RNA testing, and outcomes. Am J Gastroenterol. 2020;115(6):916-23. doi: 10.14309/ajg.0000000000000664. 
29. Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72-3. doi: 10.5582/bst.2020.01047. 
30. Ebrahimi M, Saki Malehi A, Rahim F. Laboratory findings, signs and symptoms, clinical outcomes of patients with COVID-19 infection: an updated systematic review and meta-analysis. medRxiv. 2020. doi: 10.1101/2020.03.25.20043703. 
31. Loeffelholz MJ, Tang YW. Laboratory diagnosis of emerging human coronavirus infections - the state of the art. Emerg Microbes Infect. 2020;9(1):747-56. doi: 10.1080/22221751.2020.1745095. 
32. Mungmunpuntipantip R, Wiwanitkit V. Uncertainty in using chest computed tomography in early coronavirus disease (COVID-19). Can J Anaesth. 2020;67(7):897. doi: 10.1007/s12630-020-01639-y. 
33. Pan F, Ye T, Sun P, Gui S, Liang B, Li L, et al. Time course of lung changes at chest CT during recovery from coronavirus disease 2019 (COVID-19). Radiology. 2020;295(3):715-21. doi: 10.1148/radiol.2020200370. 
34. Foroozanfar Z, Zamanian M, Moradzadeh R, Hajiabadi F, Ahmadzadeh J, Hosseinkhani Z. Isolation Compliance and Associated Factors Among COVID-19 Patients in North- West Iran: A Cross-Sectional Study. International Journal of General Medicine. 2020;13:1697. 
35. Tahvildari A, Arbabi M, Farsi Y, Jamshidi P, Hasanzadeh S, Calcagno TM, et al. Clinical features, diagnosis, and treatment of COVID-19 in hospitalized patients: a systematic review of case reports and case series. Front Med (Lausanne). 2020;7:231. doi: 10.3389/fmed.2020.00231 . 
36. Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, et al. T-cell immunity of SARS-CoV: implications for vaccine development against MERS-CoV. Antiviral Res. 2017;137:82-92. doi: 10.1016/j.antiviral.2016.11.006. 
37. Banaei M, Ghasemi V, Saei Ghare Naz M, Kiani Z, Rashidi- Fakari F, Banaei S, et al. Obstetrics and neonatal outcomes in pregnant women with COVID-19: a systematic review. Iran J Public Health. 2020;49(Suppl 1):38-47. doi: 10.18502/ ijph.v49iS1.3668. 
38. Li B, Shen J, Li L, Yu C. Radiographic and clinical features of children with coronavirus disease (COVID-19) pneumonia. Indian Pediatr. 2020;57(5):423-6. doi: 10.1007/s13312-020- 1816-8. 
39. Okba NM, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, et al. Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patients. Emerg Infect Dis. 2020;26(7):1478-88. doi: 10.3201/eid2607.200841 . 
40. Long QX, Deng HJ, Chen J, Hu JL, Liu BZ, Liao P, et al. Antibody responses to SARS-CoV-2 in COVID-19 patients: the perspective application of serological tests in clinical practice. medRxiv. 2020. doi: 10.1101/2020.03.18.20038018. 
41. Aghazadeh-Attari J, Mohebbi I, Mansorian B, Ahmadzadeh J, Mirza-Aghazadeh-Attari M, Mobaraki K, Oshnouei S. Epidemiological factors and worldwide pattern of Middle East respiratory syndrome coronavirus from 2013 to 2016. International journal of general medicine. 2018;11:121. 
42. Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26(6):845-8. doi: 10.1038/ s41591-020-0897-1. 
43. Hoffman T, Nissen K, Krambrich J, Rönnberg B, Akaberi D, Esmaeilzadeh M, et al. 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. 2020;10(1):1754538. doi: 10.1080/20008686.2020.1754538. 
44. Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J Med Virol. 2020;92(9):1518-24. doi: 10.1002/jmv.25727. 
45. Meng Z, Wang M, Song H, Guo S, Zhou Y, Li W, et al. Development and utilization of an intelligent application for aiding COVID-19 diagnosis. medRxiv. 2020. doi: 10.1101/2020.03.18.20035816. 
46. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, et al. Detection of 2019 novel coronavirus (2019- nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3). doi: 10.2807/ 
47. Alfaraj SH, Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus intermittent positive cases: Implications for infection control. Am J Infect Control. 2019;47(3):290-3. doi: 10.1016/j.ajic.2018.08.020. 
48. Wang Y, Kang H, Liu X, Tong Z. Combination of RT-qPCR testing and clinical features for diagnosis of COVID-19 facilitates management of SARS-CoV-2 outbreak. J Med Virol. 2020;92(6):538-9. doi: 10.1002/jmv.25721. 
49. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020;382(12):1177-9. doi: 10.1056/NEJMc2001737. 
50. Wang Y, Kang H, Liu X, Tong Z. Combination of RT-qPCR testing and clinical features for diagnosis of COVID-19 facilitates management of SARS-CoV-2 outbreak. J Med Virol. 2020;92(6):538-9. doi: 10.1002/jmv.25721. 
51. Long C, Xu H, Shen Q, Zhang X, Fan B, Wang C, et al. Diagnosis of the coronavirus disease (COVID-19): rRT-PCR or CT? Eur J Radiol. 2020;126:108961. doi: 10.1016/j. ejrad.2020.108961. 
52. Ai JW, Zhang Y, Zhang HC, Xu T, Zhang WH. Era of molecular diagnosis for pathogen identification of unexplained pneumonia, lessons to be learned. Emerg Microbes Infect. 2020;9(1):597-600. doi: 10.1080/22221751.2020.1738905. 
53. General Office of National Health Committee. Office of State Administration of Traditional Chinese Medicine. Notice on the issuance of strategic guidelines for diagnosis and treatment of novel coronavirus (2019-nCoV) infected pneumonia (draft)(2020-01-28)[EB/OL]. 
54. Shen C, Yu N, Cai S, Zhou J, Sheng J, Liu K, et al. Quantitative computed tomography analysis for stratifying the severity of coronavirus disease 2019. J Pharm Anal. 2020;10(2):123-9. doi: 10.1016/j.jpha.2020.03.004. 
55. Li D, Wang D, Dong J, Wang N, Huang H, Xu H, et al. False-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2: role of deep-learning-based CT diagnosis and insights from two cases. Korean J Radiol. 2020;21(4):505-8. doi: 10.3348/kjr.2020.0146. 
56. Chung M, Bernheim A, Mei X, Zhang N, Huang M, Zeng X, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology. 2020;295(1):202-7. doi: 10.1148/ radiol.2020200230. 
57. Lin X, Gong Z, Xiao Z, Xiong J, Fan B, Liu J. Novel coronavirus pneumonia outbreak in 2019: computed tomographic findings in two cases. Korean J Radiol. 2020;21(3):365-8. doi: 10.3348/kjr.2020.0078. 
58. Aghakhani N, Aliasghari A, Dejbakht M, Mobaraki K, Ahmadzadeh J. COVID-19 and Immunosuppressive Treatment after Renal Transplantation, that is the Question!-. Journal of Biomedical Research & Environmental Sciences. 2020 Sep 15;6(9):015-7.