Precision health diagnostic and surveillance network uses <i>S</i> gene target failure (SGTF) combined with sequencing technologies to track emerging SARS‐CoV‐2 variants

Guerrero‐Preston, Rafael; Rivera‐Amill, Vanessa; Caraballo, Karem; Rodríguez‐Torres, Sebastian; Purcell‐Wiltz, Ana; García, Andrea Arias; Torres, Raphael Sanchez; Zamuner, Fernando T.; Zanettini, Claudio; MacKay, Matthew; Baits, Rachel; Salgado, Daisy; Khullar, Gaurav; Baker, Timothy; Dudley, Joel T.; Vale, Keilyn; Pérez, Gabriela; Jesús, Lorena de; Miranda, Yaima; Ortiz, Denise; García‐Negrón, Amanda; Viera, Liliana; Ortiz, Alberto; Canabal, Jorge Acevedo; Romaguera, Josefina; Jiménez-Velázquez, Ivonne J.; Marchionni, Luigi; Rodríguez‐Orengo, José F.; Báez, Adriana; Mason, Christopher E.; Sidransky, David

doi:10.1002/iid3.634

Cited by 6 publications

(9 citation statements)

References 63 publications

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“…The O-BA.2 lineage does not have the 69-70 deletion [ 32 ], which correlates with the S protein being recognized by PCR tests as was the case with the Delta variant. In previous studies, samples identified as Omicron (with the exception of the BA.2 lineage and sublineages) were associated with S-gene dropout, similar to what was observed with those samples identified to be Alpha (B.1.1.7 VOC 202012/01) [ 18 , 31 ]. Samples collected and sequenced in this study were associated with the S-gene dropout mirroring the progression of Omicron detection within the population ( Figure 1 and Figure 3 ).…”

Section: Discussionsupporting

confidence: 76%

See 1 more Smart Citation

Rapid Shift from SARS-CoV-2 Delta to Omicron Sub-Variants within a Dynamic Southern U.S. Borderplex

Robles-Escajeda

Mohl

Contreras

et al. 2023

Viruses

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COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), remains an ongoing global health challenge. This study analyzed 3,641 SARS-CoV-2 positive samples from the El Paso, Texas, community and hospitalized patients over 48 weeks from Fall 2021 to Summer 2022. The binational community along the U.S. southern border was predominantly SARS-CoV-2 Delta variant (B.1.617.2) positive for a 5-week period from September 2021 to January 2022 and quickly transitioned to the Omicron variant (B.1.1.529), which was first detected at the end of December 2021. Omicron replaced Delta as the predominant detectable variant in the community and was associated with a sharp increase in COVID-19 positivity rate, related hospitalizations, and newly reported cases. In this study, Omicron BA.1, BA.4, and BA.5 variants were overwhelmingly associated with S-gene dropout by qRT-PCR analysis unlike the Delta and Omicron BA.2 variants. The study reveals that a dominant variant, like Delta, can be rapidly replaced by a more transmissible variant, like Omicron, within a dynamic metropolitan border city, necessitating enhanced monitoring, readiness, and response from public health officials and healthcare workers.

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Section: Discussionsupporting

confidence: 76%

“…The failure to detect SARS-CoV-2 S-gene in COVID-19 molecular tests is referred to as S-gene dropout or drop-off [ 18 ]. The S-gene was detected in a vast number of samples during wk 36-2021 to wk 49-2021 ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

Rapid Shift from SARS-CoV-2 Delta to Omicron Sub-Variants within a Dynamic Southern U.S. Borderplex

Robles-Escajeda

Mohl

Contreras

et al. 2023

Viruses

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“…Many publications have evaluated different approaches to determining the accuracy and applicability of the SGTF in variant detection [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. In our study, the sensitivity and specificity values based on WGS VOC determination were in line with previously reported values [ 34 ]; our calculations based on variant-specific PCR, however, were consistently lower than for WGS, indicating a reduced accuracy in lineage classification.…”

Section: Discussionmentioning

confidence: 99%

S-Gene Target Failure as an Effective Tool for Tracking the Emergence of Dominant SARS-CoV-2 Variants in Switzerland and Liechtenstein, Including Alpha, Delta, and Omicron BA.1, BA.2, and BA.4/BA.5

Hilti,

Wehrli,

Berchtold

et al. 2024

Microorganisms

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During the SARS-CoV-2 pandemic, the Dr. Risch medical group employed the multiplex TaqPathTM COVID-19 CE-IVD RT-PCR Kit for large-scale routine diagnostic testing in Switzerland and the principality of Liechtenstein. The TaqPath Kit is a widely used multiplex assay targeting three genes (i.e., ORF1AB, N, S). With emergence of the B.1.1.7 (Alpha) variant, a diagnostic flaw became apparent as the amplification of the S-gene target was absent in these samples due to a deletion (ΔH69/V70) in the Alpha variant genome. This S-gene target failure (SGTF) was the earliest indication of a new variant emerging and was also observed in subsequent variants such as Omicron BA.1 and BA4/BA.5. The Delta variant and Omicron BA.2 did not present with SGTF. From September 2020 to November 2022, we investigated the applicability of the SGTF as a surrogate marker for emerging variants such as B.1.1.7, B.1.617.2 (Delta), and Omicron BA.1, BA.2, and BA.4/BA.5 in samples with cycle threshold (Ct) values < 30. Next to true SGTF-positive and SGTF-negative samples, there were also samples presenting with delayed-type S-gene amplification (higher Ct value for S-gene than ORF1ab gene). Among these, a difference of 3.8 Ct values between the S- and ORF1ab genes was found to best distinguish between “true” SGTF and the cycle threshold variability of the assay. Samples above the cutoff were subsequently termed partial SGTF (pSGTF). Variant confirmation was performed by whole-genome sequencing (Oxford Nanopore Technology, Oxford, UK) or mutation-specific PCR (TIB MOLBIOL). In total, 17,724 (7.4%) samples among 240,896 positives were variant-confirmed, resulting in an overall sensitivity and specificity of 93.2% [92.7%, 93.7%] and 99.3% [99.2%, 99.5%], respectively. Sensitivity was increased to 98.2% [97.9% to 98.4%] and specificity lowered to 98.9% [98.6% to 99.1%] when samples with pSGTF were included. Furthermore, weekly logistic growth rates (α) and sigmoid’s midpoint (t0) were calculated based on SGTF data and did not significantly differ from calculations based on comprehensive data from GISAID. The SGTF therefore allowed for a valid real-time estimate for the introduction of all dominant variants in Switzerland and Liechtenstein.

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“…Whatever the reason may be, this pandemic has made known that due to deficient molecular surveillance, we were unable to identify and monitor the viral pathogen spread among the community [3].…”

Section: Introductionmentioning

confidence: 99%

To Analyze the Sensitivity of RT-PCR Assays Employing S Gene Target Failure with Whole Genome Sequencing Data during Third Wave by SARS-CoV-2 Omicron Variant

Patel,

Mistry,

Patel

et al. 2024

AiM

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Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence; it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618

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Precision health diagnostic and surveillance network uses S gene target failure (SGTF) combined with sequencing technologies to track emerging SARS‐CoV‐2 variants

Cited by 6 publications

References 63 publications

Rapid Shift from SARS-CoV-2 Delta to Omicron Sub-Variants within a Dynamic Southern U.S. Borderplex

Rapid Shift from SARS-CoV-2 Delta to Omicron Sub-Variants within a Dynamic Southern U.S. Borderplex

S-Gene Target Failure as an Effective Tool for Tracking the Emergence of Dominant SARS-CoV-2 Variants in Switzerland and Liechtenstein, Including Alpha, Delta, and Omicron BA.1, BA.2, and BA.4/BA.5

To Analyze the Sensitivity of RT-PCR Assays Employing S Gene Target Failure with Whole Genome Sequencing Data during Third Wave by SARS-CoV-2 Omicron Variant

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