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Clinical validation of optimised RT-LAMP for the diagnosis of SARS-CoV-2 infection

Abstract:
We have optimised a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of SARS-CoV-2 from extracted RNA for clinical application. We improved the stability and reliability of the RT-LAMP assay by the addition of a temperature-dependent switch oligonucleotide to reduce self- or off-target amplification. We then developed freeze-dried master mix for single step RT-LAMP reaction, simplifying the operation for end users and improving long-term storage and transportation. The assay can detect as low as 13 copies of SARS-CoV2 RNA per reaction (25-μL). Cross reactivity with other human coronaviruses was not observed. We have applied the new RT-LAMP assay for testing clinical extracted RNA samples extracted from swabs of 72 patients in the UK and 126 samples from Greece and demonstrated the overall sensitivity of 90.2% (95% CI 83.8–94.7%) and specificity of 92.4% (95% CI 83.2–97.5%). Among 115 positive samples which Ct values were less than 34, the RT-LAMP assay was able to detect 110 of them with 95.6% sensitivity. The specificity was 100% when RNA elution used RNase-free water. The outcome of RT-LAMP can be reported by both colorimetric detection and quantifiable fluorescent reading. Objective measures with a digitized reading data flow would allow for the sharing of results for local or national surveillance.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41598-021-95607-1

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Role:
Author
ORCID:
0000-0001-6513-194X
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Role:
Author
ORCID:
0000-0001-6522-138X
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Role:
Author
ORCID:
0000-0002-6607-6353


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Funding agency for:
Andersson, M
Cui, Z
Huang, W
Programme:
COVID-19 Research Response Fund


Publisher:
Springer Nature
Journal:
Scientific Reports More from this journal
Volume:
11
Issue:
1
Article number:
16193
Publication date:
2021-08-10
Acceptance date:
2021-07-21
DOI:
EISSN:
2045-2322


Language:
English
Keywords:
Pubs id:
1178371
Local pid:
pubs:1178371
Deposit date:
2021-05-25

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