Considerations in Real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) for the Detection of SARS-CoV-2 from Nasopharyngeal Swabs
Journal of Pharmaceutical Research International,
Page 68-78
DOI:
10.9734/jpri/2021/v33i1731309
Abstract
Coronavirus Disease 2019 (COVID-19) was first reported in December 2019, in the City of Wuhan, China. Within the span of a few weeks, the disease had spread to other regions of China and eventually to different parts of the world. COVID 19 has affected 221 countries and territories around the world, with a total of 121,290,697 positive cases and 2,682,554 deaths as on March 17, 2021. Accurate disease diagnosis (for the SARS-Cov-2 virus and variants), coupled to patient isolation are currently critical strategies in restricting disease spread. Due to lack of time during this pandemic the diagnostics assays were not adequately validated. Infected individuals at times could potentially be missed by real-time reverse transcription polymerase chain reaction (rRT-PCR) for SARS-CoV-2 tests due to incorrect/inefficient sampling procedure, low limit of detection and epidemiology of the virus. rRT-PCR test results should be interpreted in conjunction with clinical examination and Computed Tomography (CT), particularly in suspected symptomatic individuals or those with epidemiological history of contact with known COVID-19 cases. Considering the above-mentioned constraints, the current scenario demands rapid and point-of-care tests for detection of SARS-CoV-2 in remote locations. To date, there is no reliable commercially available antigen detection kit. The infected subjects reveal low levels of antibodies against SARS-CoV-2 through the early period of infection. In addition, techniques such as, Digital RT-PCR technology and isothermal RNA amplification with electrochemical biosensors are some of the new technologies currently being developed to provide sensitive and specific SARS-Cov-2 antigen detection. The newly reported variant, SARS-CoV-2 VUI 202012/01 may not influence diagnostic outcomes as worldwide most PCR assays use two or more (including RdRp/ E/ N) reliable gene targets, besides S gene.
Keywords:
- COVID-19
- SARS-CoV-2
- real-time RT PCR
- techniques
- validation
- results
How to Cite
Sekar, P., Menezes, G. A., Shivappa, P., George, B. T. and Hossain, A. (2021) “Considerations in Real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) for the Detection of SARS-CoV-2 from Nasopharyngeal Swabs”, Journal of Pharmaceutical Research International, 33(17), pp. 68-78. doi: 10.9734/jpri/2021/v33i1731309.
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Published: 2020 Nov 10.
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DOI: 10.7883/yoken.JJID.2020.108.
Epub: 2020 Apr 30.
PMID: 32350226.
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DOI: 10.1128/JCM.00310-20.
PMID: 32132196;
PMCID: PMC7180250.
Corman VM, Landt O, Kaiser M, Molen kamp R, Meijer A, Chu DK, et al. Detection of 2019 novel corona virus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3):2000045.
DOI: 10.2807/1560-7917. ES.2020. 25.3.2000045.
Erratum in: Euro Surveill. 2020 Apr;25(14): Euro Surveill. 2020 Jul;25(30)
PMID: 31992387;
PMCID: PMC6988269.
Wu Y, Xu W, Zhu Z, Xia X. Laboratory verification of an RT-PCR assay for SARS-CoV-2. J Clin Lab Anal. 2020;34:e23507.
DOI: https://doi.org/10.1002/jcla.23507
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Chang MC, Hur J, Park D. Interpreting the COVID-19 test results: A guide for physiatrists. Am J Phys Med Rehabil. 2020;99(7):583–585.
DOI:https://doi.org/10.1097/PHM.0000000000001471.
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Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020;9:221–236.
DOI: 10.1080/22221751.2020.1719902.
Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. Middle East respiratory syndrome corona virus: Another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev. 2015;28:465–522.
DOI: 10.1128/CMR.00102-14.
WHO. All technical guidance on COVID-19 - select topic from drop down menu; 2020.
Available:https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance-publications.
Accessed: 27 Dec. 2020.
Chu DKW, Pan Y, Cheng SMS, Hui KPY, Krishnan P, Liu Y, Ng DYM, et al. Molecular diagnosis of a novel corona virus (2019-nCoV) causing an outbreak of pneumonia. Clin Chem. 2020;66(4):549-555.
DOI: 10.1093/clinchem/hvaa029.
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DOI: 10.1016/j.medj.2020.08.001
Peñarrubia L, Ruiz M, Porco R, Rao SN, Juanola-Falgarona M, Manissero D, ET AL. Multiple assays in a real-time RT-PCR SARS-CoV-2 panel can mitigate the risk of loss of sensitivity by new genomic variants during the COVID-19 outbreak. Int J Infect Dis. 2020;97:225-229.
DOI: 10.1016/j.ijid.2020.06.027.
Epub: 2020 Jun 12.
PMID: 32535302;
PMCID: PMC7289722.
Rao SN, Manissero D, Steele VR, Pareja J. Correction to: A systematic review of the clinical utility of cycle threshold values in the context of COVID-19. Infectious Diseases and Therapy. 2020;9(3):587.
DOI: 10.1007/s40121-020-00328-z.
Alonso F de OM, Sabino BD, Guimarães MAAM, Varella RB. Recurrence of SARS-CoV-2 infection with a more severe case after mild COVID-19, reversion of RT-qPCR for positive and late antibody response: Case report. J Med Virol 2020; 14;10.1002/jmv.26432.
DOI: 10.1002/jmv.26432.
Zou L, Ruan F, Huang M, Liang L, Huang H, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020;19;382(12):1177-1179.
DOI: 10.1056/NEJMc2001737.
Epub: 2020 Feb 19.
PMID: 32074444;
PMCID: PMC7121626.
Li Y, Yao L, Li J, Chen L, Song Y, Cai Z. Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19. J Med Virol. 2020;92(7):903-908.
DOI: 10.1002/jmv.25786.
Microchip RT-PCR COVID-19 (SARS-CoV-2) detection system. Lumex Instrum - Lab Anal Equip Manuf; 2020.
Available:https://www.lumexinstruments.com/applications/covid-19_detection_ system.php
Accessed: June 13, 2020).
Ji T, Liu Z, Wang G, Guo X, Akbar Khan S, Lai C, et al. Detection of COVID-19: A review of the current literature and future perspectives. Biosens Bioelectron. 2020; 166:112455.
DOI: 10.1016/j.bios.2020.112455.
Epub: 2020 Jul 21.
PMID: 32739797;
PMCID: PMC7371595.
Li C, Ren L. Recent progress on the diagnosis of 2019 Novel Corona virus. Transbound Emerg Dis. 2020;67(4):1485-1491.
DOI: 10.1111/tbed.13620.
Epub: 2020 May 31.
PMID: 32395897;
PMCID: PMC7272792.
WHO. SARS-CoV-2 variant – United Kingdom of Great Britain and Northern Ireland. Disease Outbreak News; 2020.
Available:https://www.who.int/csr/don/21-december-2020-sars-cov2-variant-united-kingdom/en/
Accessed: 27 Dec 2020.
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