Clinical Performance Characteristics of the Swift Normalase Amplicon Panel for Sensitive Recovery of Severe Acute Respiratory Syndrome Coronavirus 2 Genomes

Shrestha, Lasata; Lin, Michelle J.; Xie, Hong; Mills, Margaret G.; Bakhash, Shah A Mohamed; Gaur, Vinod P.; Livingston, Robert; Castor, Jared; Bruce, Emily A.; Botten, Jason; Huang, Meei‐Li; Jerome, Keith R.; Greninger, Alexander L.; Roychoudhury, Pavitra

doi:10.1016/j.jmoldx.2022.05.007

Cited by 9 publications

(7 citation statements)

References 54 publications

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“…Viral genomic sequencing was performed on respiratory samples from the cases to identify the SARS-CoV-2 variant, as previously described. 16,17 Efficacy endpoints…”

Section: Interventions and Assessmentsmentioning

confidence: 99%

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine

Dayan

Rouphael

Walsh

et al. 2022

Preprint

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Background COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. Methods We conducted a global Phase 3, multi-stage efficacy study (NCT04904549) among adults aged ≥18 years. Participants were randomized 1:1 to receive two intramuscular injections 21 days apart of a bivalent SARS-CoV-2 recombinant protein vaccine with AS03-adjuvant (5 μg of ancestral (D614) and 5 μg of B.1.351 [beta] variant spike protein) or placebo. Symptomatic COVID-19 was defined as laboratory-confirmed COVID-19 with COVID-19-like illness (CLI) symptoms. The primary efficacy endpoint was the prevention of symptomatic COVID-19 ≥14 days after the second injection. Results Between 19 Oct 2021 and 15 Feb 2022, 12,924 participants received ≥1 study injection. 75% of participants were SARS-CoV-2 non-naïve. 11,416 participants received both study injections (efficacy-evaluable population [vaccine, n=5,736; placebo, n=5,680]). Up to 15 March 2022, 121 symptomatic COVID-19 cases were reported (32 in the vaccine group and 89 in the placebo group) ≥14 days after the second injection with a vaccine efficacy (VE) of 64.7% (95% confidence interval [CI] 46.6; 77.2%). VE was 75.1% (95% CI 56.3; 86.6%) in non-naïve and 30.9% (95% CI -39.3; 66.7%) in naïve participants. Viral genome sequencing identified the infecting strain in 68 cases (Omicron [BA.1 and BA.2 subvariants]: 63; Delta: 4; Omicron and Delta: 1). The vaccine was well-tolerated and had an acceptable safety profile. Conclusions A bivalent vaccine conferred heterologous protection against symptomatic infection with newly emergent Omicron (BA.1 and BA.2) in non-naïve adults 18-59 years of age. ClinicalTrials.gov:NCT04904549

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“…Viral genomic sequencing was performed on respiratory samples from the cases to identify the SARS-CoV-2 variant, as previously described. 16,17 Efficacy endpoints…”

Section: Interventions and Assessmentsmentioning

confidence: 99%

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine

Dayan

Rouphael

Walsh

et al. 2022

Preprint

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“…Sequencing of remnant clinical specimens at UW Virology Lab was approved by the University of Washington Institutional Review Board with a waiver of informed consent (protocol STUDY00000408). Nasopharyngeal, nasal, or oropharyngeal swabs with PCR cycle threshold <31 were randomly selected and sequenced as described previously 73 . Briefly, after RNA extraction, library preparation was performed using the Illumina COVIDseq protocol with ARTIC v4.1 primers (Integrated DNA Technologies).…”

Section: Methodsmentioning

confidence: 99%

Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution

Wagner,

Kistler,

Perchetti

et al. 2024

Nat Commun

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Knockout of the ORF8 protein has repeatedly spread through the global viral population during SARS-CoV-2 evolution. Here we use both regional and global pathogen sequencing to explore the selection pressures underlying its loss. In Washington State, we identified transmission clusters with ORF8 knockout throughout SARS-CoV-2 evolution, not just on novel, high fitness viral backbones. Indeed, ORF8 is truncated more frequently and knockouts circulate for longer than for any other gene. Using a global phylogeny, we find evidence of positive selection to explain this phenomenon: nonsense mutations resulting in shortened protein products occur more frequently and are associated with faster clade growth rates than synonymous mutations in ORF8. Loss of ORF8 is also associated with reduced clinical severity, highlighting the diverse clinical impacts of SARS-CoV-2 evolution.

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“…SARS-CoV-2 sequencing was limited to samples with >40 copies/polymerase chain reaction, which corresponds to the lower limit of detection for the sequencing assay (approximately 600 copies/mL). The whole genome of SARS-CoV-2 was amplified using the Swift Bioscience SARS-CoV-2 assay, and the nucleotide sequence was determined by Illumina NextSeq 500 or NextSeq 2000 (Illumina, Inc) at the University of Washington Virology Laboratory (Seattle, WA) [ 24 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1)

Hedskog

Rodriguez

Roychoudhury

et al. 2023

The Journal of Infectious Diseases

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Background Remdesivir is approved for the treatment of COVID-19 in non-hospitalized and hospitalized adult and pediatric patients. Here we present SARS-CoV-2 resistance analyses from the Phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19. Methods Swab samples were collected at baseline and longitudinally through Day 29. SARS-CoV-2 genomes were sequenced using next-generation sequencing. Phenotypic analysis was conducted directly on participant virus isolates and/or using SARS-CoV-2 subgenomic replicons expressing mutations identified in the Nsp12 target gene. Results Among participants with both baseline and post-baseline sequencing data, emergent Nsp12 substitutions were observed in 12/31 (38.7%) and 12/30 (40.0%) participants in the remdesivir and placebo arms, respectively. No emergent Nsp12 substitutions in the remdesivir arm were observed in more than one participant. Phenotyping showed low to no change in susceptibility to remdesivir relative to wild-type Nsp12 reference for the substitutions tested: A16V (0.8-fold change in EC50), P323L+V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N+V792I (3.4-fold). Conclusions The similar rate of emerging Nsp12 substitutions in remdesivir and placebo arms and the minimal change in remdesivir susceptibility among tested substitutions support a high barrier to remdesivir resistance development in COVID-19 patients.

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Clinical Performance Characteristics of the Swift Normalase Amplicon Panel for Sensitive Recovery of Severe Acute Respiratory Syndrome Coronavirus 2 Genomes

Cited by 9 publications

References 54 publications

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine

Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution

Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1)

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