SARS-CoV-2 genome diversity at the binding sites of oligonucleotides used for COVID-19 diagnosis
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Le résumé fourni par la source
Abstract Importance SARS-CoV-2 genomic variants impacts the overall sensitivity of COVID-19 diagnosis, leading to false-negative diagnosis and the continued spread of the virus. Objective To evaluate how nucleotide variability in target primer binding sites of the SARS-CoV-2 genomes may impact diagnosis using different recommended primer/probe sets, as well as to suggest the best primer/probes for diagnosis. Design We downloaded 105,118 public SARS-CoV-2 genomes from GISAID (Sept, 25th, 2020), removed genomes of apparent worst quality (genome length <29kb and/or >5% ambiguous bases) and missing metadata, and performed an analysis of complementarity for the 13 most used diagnostic primers/probe sets for RT-PCR detection. We calculated the N rate and % of genome recovery, with all primer/probe-sets considering viral origin and clade. Results: Our findings indicate that currently, the Paris_nCoV-IP2, -IP4 and WHO|E_Sarbeco primer/probe sets for COVID-19, to perform the best diagnostically worldwide, recovering >99.5% of the good quality SARS-CoV-2 genomes from GISAID, with no mismatches. The Chinese_CDC|2019-nCoV-NP primer/probe set, among the first to be designed during the pandemic, was the most susceptible to currently most abundant SARS-CoV-2 variants. Mismatches encompassing the binding sites for this set are more frequent in Clade-GR and are highly prevalent in over 30 countries globally, including Brazil and India, two of the hardest hit countries. Conclusions: Detection of SARS-CoV-2 in patients may be hampered by significant variability in parts of the viral genome that are targeted by some widely used primer sets. The geographic distribution of different viral clades indicates that continuous assessment of primer sets via sequencing-based surveillance and viral evolutionary analysis is critical to accurate diagnostics. This study highlights sequence variance in target regions that may reduce the efficiency of primer:target hybridization that in turn may lead to the undetected spread of the virus. As such, due to this variance, the Chinese_CDC|2019-nCoV-NP-set should be used with caution, or avoided, especially in countries with high prevalence of the GR clade. Key Points Question How variable are the binding-sites of primers/probes used for COVID-19 diagnosis? Findings We investigated nucleotide variations in primer-binding sites used for COVID-19 diagnosis, in 93,143 SARS-CoV-2 genomes, and found primer sets targeting regions of increasingly nucleotide variance over time, such as the Chinese_CDC|2019-nCoV-NP. The frequency of these variations is higher in Clade-GR whose frequency is increasing worldwide. Paris_nCoV-IP2, IP4 and WHO|E_Sarbeco performed best. Meaning We suggest the use of some sets to be halted and reinforce the importance of a continuous surveillance of SARS-CoV-2 variations to prompt the use of the best primers.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- SARS-CoV-2 genome diversity at the binding sites of oligonucleotides used for COVID-19 diagnosis
- Date Crossref
- 11/12/2020
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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AC Camargo Hospital pays non établi dans la noticeÉtablissement de santé
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Jagiellonian University Małopolska Centre of Biotechnology pays non établi dans la noticeUniversité ou école supérieure
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National Academy of Sciences of Ukraine pays non établi dans la noticeOrganisme public
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Institute of Molecular Biology and Genetics pays non établi dans la noticeOrganisme public
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Cornell University pays non établi dans la noticeUniversité ou école supérieure
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Weill Cornell Medicine pays non établi dans la noticeUniversité ou école supérieure
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Jet Propulsion Laboratory pays non établi dans la noticeStructure de recherche
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City University of New York Dept. of Biology pays non établi dans la noticeUniversité ou école supérieure
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Swedish University of Agricultural Sciences pays non établi dans la noticeUniversité ou école supérieure
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MIND Research Institute pays non établi dans la noticeOrganisation à but non lucratif
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Universidade de São Paulo Faculdade de Medicina pays non établi dans la noticeUniversité ou école supérieure
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Lab. of Computational Biology and Bioinformatics pays non établi dans la noticeInstitution
AC Camargo Hospital, Małopolska Centre of Biotechnology — Jagiellonian University et National Academy of Sciences of Ukraine, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.