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. 2022 Jun;10(6):e634.
doi: 10.1002/iid3.634.

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

Rafael Guerrero-Preston  1 , Vanessa Rivera-Amill  2 , Karem Caraballo  1 , Sebastian Rodríguez-Torres  3 , Ana Purcell-Wiltz  1   4 , Andrea A García  2 , Raphael S Torres  2 , Fernando T Zamuner  5 , Claudio Zanettini  6 , Matthew J MacKay  7 , Rachel Baits  7 , Daisy Salgado  7 , Gaurav Khullar  7 , Jessica Metti  7 , Timothy Baker  7 , Joel Dudley  7 , Keilyn Vale  1 , Gabriela Pérez  8 , Lorena De Jesús  1 , Yaima Miranda  1 , Denise Ortiz  1 , Amanda García-Negrón  1 , Liliana Viera  9 , Alberto Ortiz  10 , Jorge A Canabal  10 , Josefina Romaguera  11 , Ivonne Jiménez-Velázquez  10 , Luigi Marchionni  5 , José F Rodríguez-Orengo  12 , Adriana Baez  13 , Christopher E Mason  7 , David Sidransky  5
Affiliations

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

Rafael Guerrero-Preston et al. Immun Inflamm Dis. 2022 Jun.

Abstract

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic revealed a worldwide lack of effective molecular surveillance networks at local, state, and national levels, which are essential to identify, monitor, and limit viral community spread. SARS-CoV-2 variants of concern (VOCs) such as Alpha and Omicron, which show increased transmissibility and immune evasion, rapidly became dominant VOCs worldwide. Our objective was to develop an evidenced-based genomic surveillance algorithm, combining reverse transcription polymerase chain reaction (RT-PCR) and sequencing technologies to quickly identify highly contagious VOCs, before cases accumulate exponentially.

Methods: Deidentified data were obtained from 508,969 patients tested for coronavirus disease 2019 (COVID-19) with the TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) in four CLIA-certified clinical laboratories in Puerto Rico (n = 86,639) and in three CLIA-certified clinical laboratories in the United States (n = 422,330).

Results: TaqPath data revealed a frequency of S Gene Target Failure (SGTF) > 47% for the last week of March 2021 in both, Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in March 2021. The weekly SGTF rate in US samples was high (>8%) from late December to early January and then also increased exponentially through April (48%). The exponential increase in SGFT prevalence in Puerto Rico was concurrent with a sharp increase in VOCs among all SARS-CoV-2 sequences from Puerto Rico uploaded to Global Influenza Surveillance and Response System (GISAID) (n = 461). Alpha variant frequency increased from <1% in the last week of January 2021 to 51.5% of viral sequences from Puerto Rico collected in the last week of March 2021.

Conclusions: According to the proposed evidence-based algorithm, approximately 50% of all SGTF patients should be managed with VOCs self-quarantine and contact tracing protocols, while WGS confirms their lineage in genomic surveillance laboratories. Our results suggest this workflow is useful for tracking VOCs with SGTF.

Keywords: SARS-CoV-2; algorithms; genomics; population surveillance; precision medicine; public health.

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Conflict of interest statement

Matthew J. MacKay, Rachel Baits, Daisy Salgado, Gaurav Khullar, Jessica Metti, Timothy Baker, Joel Dudley, and Christopher E. Mason, work for Tempus Labs. Rafael Guerrero‐Preston works for LifeGene‐Biomarks. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Frequency of S gene target failure (SGTF) in samples from Connecticut, Illinois, New Jersey, New York, and Puerto Rico from December 2020 through March 2021.
Figure 2
Figure 2
Frequency of SARS‐CoV‐2 variants in samples from Puerto Rico in GISAID, as of April 18, 2021 (n = 461), by lineage. GISAID, Global Influenza Surveillance and Response System; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.
Figure 3
Figure 3
Mean daily lag time between sample collection and sequencing date from February 2020 through March 31, 2021, in Connecticut, Illinois, New Jersey, New York, and Puerto Rico.
Figure 4
Figure 4
Variant of Concern Identification Algorithm diagram.
See this image and copyright information in PMC

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Supplementary concepts