High-Throughput Adaptable SARS-CoV-2 Screening for Rapid Identification of Dominant and Emerging Regional Variants.

Zita Hubler, Xiao Song, Cameron Norris, Mehul Jani, David Alouani, Maureen Atchley, Lisa Stempak, Sarah Cherian, Christine Schmotzer, Navid Sadri
Author Information
  1. Zita Hubler: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  2. Xiao Song: Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  3. Cameron Norris: Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  4. Mehul Jani: Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  5. David Alouani: Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  6. Maureen Atchley: Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  7. Lisa Stempak: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  8. Sarah Cherian: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  9. Christine Schmotzer: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  10. Navid Sadri: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. ORCID

Abstract

OBJECTIVES: Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains can be associated with increased transmissibility, more severe disease, and reduced effectiveness of treatments. To improve the availability of regional variant surveillance, we describe a variant genotyping system that is rapid, accurate, adaptable, and able to detect new low-level variants built with existing hospital infrastructure.
METHODS: We used a tiered high-throughput SARS-CoV-2 screening program to characterize variants in a supraregional health system over 76 days. Combining targeted reverse transcription-polymerase chain reaction (RT-PCR) and selective sequencing, we screened SARS-CoV-2 reactive samples from all hospitals within our health care system for genotyping dominant and emerging variants.
RESULTS: The median turnaround for genotyping was 2 days using the high-throughput RT-PCR-based screen, allowing us to rapidly characterize the emerging Delta variant. In our population, the Delta variant is associated with a lower cycle threshold value, lower age at infection, and increased vaccine-breakthrough cases. Detection of low-level and potentially emerging variants highlights the utility of a tiered approach.
CONCLUSIONS: These findings underscore the need for fast, low-cost, high-throughput monitoring of regional viral sequences as the pandemic unfolds and the emergence of SARS-CoV-2 variants increases. Combining RT-PCR-based screening with selective sequencing allows for rapid genotyping of variants and dynamic system improvement.

Keywords

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Grants

  1. F30 MH116581/NIMH NIH HHS
  2. T32 GM007250/NIGMS NIH HHS
  3. TL1 TR002549/NCATS NIH HHS

MeSH Term

COVID-19
High-Throughput Screening Assays
Humans
Pandemics
SARS-CoV-2

Word Cloud

Created with Highcharts 10.0.0SARS-CoV-2variantvariantsgenotypingsystemhigh-throughputscreeningemergingDeltaVariantEmergingsevere2associatedincreasedregionalrapidlow-leveltieredcharacterizehealthdaysCombiningselectivesequencingRT-PCR-basedlowerOBJECTIVES:acuterespiratorysyndromecoronavirusstrainscantransmissibilitydiseasereducedeffectivenesstreatmentsimproveavailabilitysurveillancedescribeaccurateadaptableabledetectnewbuiltexistinghospitalinfrastructureMETHODS:usedprogramsupraregional76targetedreversetranscription-polymerasechainreactionRT-PCRscreenedreactivesampleshospitalswithincaredominantRESULTS:medianturnaroundusingscreenallowingusrapidlypopulationcyclethresholdvalueageinfectionvaccine-breakthroughcasesDetectionpotentiallyhighlightsutilityapproachCONCLUSIONS:findingsunderscoreneedfastlow-costmonitoringviralsequencespandemicunfoldsemergenceincreasesallowsdynamicimprovementHigh-ThroughputAdaptableScreeningRapidIdentificationDominantRegionalVariantsE484KTargetedtestingidentificationconcern

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