A novel ORF1a-based SARS-CoV-2 RT-PCR assay to resolve inconclusive samples.


Journal

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
ISSN: 1878-3511
Titre abrégé: Int J Infect Dis
Pays: Canada
ID NLM: 9610933

Informations de publication

Date de publication:
May 2021
Historique:
received: 04 02 2021
revised: 31 03 2021
accepted: 04 04 2021
pubmed: 15 4 2021
medline: 28 5 2021
entrez: 14 4 2021
Statut: ppublish

Résumé

India bears the second largest burden of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. A multitude of reverse transcription polymerase chain reaction (RT-PCR) detection assays with disparate gene targets, including automated high-throughput platforms, are available. Varying concordance and interpretation of diagnostic results in this setting can result in significant reporting delays, leading to suboptimal disease management. This article reports the development of a novel ORF1a-based SARS-CoV-2 RT-PCR assay - Viroselect - that shows high concordance with conventional assays and the ability to resolve inconclusive results generated during the peak of the epidemic in Mumbai, India. A unique target region within SARS-CoV-2 ORF1a - the non-structural protein 3 (nsp3) region - was used to design and develop the assay. This hypervariable region (1923-3956) between SARS-CoV-2, SARS-CoV-1 and Middle East respiratory syndrome coronavirus was utilized to design the primers and probes for the RT-PCR assay. The concordance of this assay with commonly used emergency use authorization (US Food and Drug Administration) manual kits and an automated high-throughput testing platform was evaluated. Further, a retrospective analysis was carried out using Viroselect on samples reported as 'inconclusive' between April and October 2020. In total, 701 samples were tested. Concordance analysis of 477 samples demonstrated high overall agreement of Viroselect with both manual (87.6%) and automated (84.7%) assays. Also, in the retrospective analysis of 224 additional samples reported as 'inconclusive', Viroselect was able to resolve 100% (19/19) and 93.7% (192/205) of samples which had inconclusive results on manual and automated high-throughput platforms, respectively. Viroselect had high concordance with conventional assays, both manual and automated, and has potential to resolve inconclusive samples.

Sections du résumé

BACKGROUND BACKGROUND
India bears the second largest burden of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. A multitude of reverse transcription polymerase chain reaction (RT-PCR) detection assays with disparate gene targets, including automated high-throughput platforms, are available. Varying concordance and interpretation of diagnostic results in this setting can result in significant reporting delays, leading to suboptimal disease management. This article reports the development of a novel ORF1a-based SARS-CoV-2 RT-PCR assay - Viroselect - that shows high concordance with conventional assays and the ability to resolve inconclusive results generated during the peak of the epidemic in Mumbai, India.
METHODS METHODS
A unique target region within SARS-CoV-2 ORF1a - the non-structural protein 3 (nsp3) region - was used to design and develop the assay. This hypervariable region (1923-3956) between SARS-CoV-2, SARS-CoV-1 and Middle East respiratory syndrome coronavirus was utilized to design the primers and probes for the RT-PCR assay. The concordance of this assay with commonly used emergency use authorization (US Food and Drug Administration) manual kits and an automated high-throughput testing platform was evaluated. Further, a retrospective analysis was carried out using Viroselect on samples reported as 'inconclusive' between April and October 2020.
RESULTS RESULTS
In total, 701 samples were tested. Concordance analysis of 477 samples demonstrated high overall agreement of Viroselect with both manual (87.6%) and automated (84.7%) assays. Also, in the retrospective analysis of 224 additional samples reported as 'inconclusive', Viroselect was able to resolve 100% (19/19) and 93.7% (192/205) of samples which had inconclusive results on manual and automated high-throughput platforms, respectively.
CONCLUSION CONCLUSIONS
Viroselect had high concordance with conventional assays, both manual and automated, and has potential to resolve inconclusive samples.

Identifiants

pubmed: 33852938
pii: S1201-9712(21)00317-9
doi: 10.1016/j.ijid.2021.04.006
pmc: PMC8036167
pii:
doi:

Substances chimiques

ORF1ab polyprotein, SARS-CoV-2 0
Polyproteins 0
Viral Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

395-400

Informations de copyright

Copyright © 2021. Published by Elsevier Ltd.

Auteurs

Ketki Jawade (K)

Department of Biochemistry and Virology, ICMR-NRRH, Mumbai, India.

Akhauri Yash Sinha (AY)

Bencos Research Solutions Pvt. Ltd., Mumbai, India.

Sharad Bhagat (S)

Department of Biochemistry and Virology, ICMR-NRRH, Mumbai, India.

Shilpa Bhowmick (S)

Department of Biochemistry and Virology, ICMR-NRRH, Mumbai, India.

Bhagyashree Chauhan (B)

Bencos Research Solutions Pvt. Ltd., Mumbai, India.

Snehal Kaginkar (S)

Department of Biochemistry and Virology, ICMR-NRRH, Mumbai, India.

Harsha Palav (H)

Department of Biochemistry and Virology, ICMR-NRRH, Mumbai, India.

Nandini Kasarpalkar (N)

Department of Molecular Immunology and Microbiology, ICMR-NIRRH, Mumbai, India.

Pratik Devadiga (P)

Department of Molecular Immunology and Microbiology, ICMR-NIRRH, Mumbai, India.

Kalyani Karandikar (K)

Department of Molecular Immunology and Microbiology, ICMR-NIRRH, Mumbai, India.

Sachee Agrawal (S)

Molecular Laboratory, Kasturba Hospital for Infectious Diseases, Mumbai, India; Department of Microbiology, BYL Nair Hospital, Mumbai, India.

Jayanthi Shastri (J)

Molecular Laboratory, Kasturba Hospital for Infectious Diseases, Mumbai, India; Department of Microbiology, BYL Nair Hospital, Mumbai, India.

Kiran Munne (K)

Department of Clinical Research, ICMR-NIRRH, Mumbai, India.

Vikrant M Bhor (VM)

Department of Molecular Immunology and Microbiology, ICMR-NIRRH, Mumbai, India.

Smita D Mahale (SD)

Department of Structural Biology Division, ICMR-NIRRH, Mumbai, India.

Subhanjan Bhowmik (S)

Bencos Research Solutions Pvt. Ltd., Mumbai, India.

Dhanashree Jagtap (D)

Department of Structural Biology Division, ICMR-NIRRH, Mumbai, India. Electronic address: jagtapd@nirrh.res.in.

Vainav Patel (V)

Department of Biochemistry and Virology, ICMR-NRRH, Mumbai, India. Electronic address: patelv@nirrh.res.in.

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