S-Variant SARS-CoV-2 Lineage B1.1.7 Is Associated With Significantly Higher Viral Load in Samples Tested by TaqPath Polymerase Chain Reaction

Kidd, Michael; Richter, Alex; Best, Angus; Cumley, Nicola; Mirza, Jeremy; Percival, Benita; Mayhew, Megan; Megram, Oliver; Ashford, Fiona; White, Thomas; Moles-Garcia, Emma; Crawford, Liam; Bosworth, Andrew; Atabani, Sowsan; Plant, Tim; McNally, Alan

doi:10.1093/infdis/jiab082

Cited by 222 publications

(207 citation statements)

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“…Negligible differences were seen in other ORF sgRNA (Figure S2). Consistent with previous findings ( 6, 15 ), we also found significantly decreased E gene Ct (ECT; in house diagnostic assay ( 16 ); B.1.177 median=25, B.1.1.7 median=23) and significantly greater Relative Light Units (RLU; Hologic Panther platform; B.1.177 median=1121, B.1.1.7 median = 1177) in B.1.1.7 infections compared to B.1.177 infections (Figure 1E&F). Accordingly, total mapped reads and total genomic RNA reads (i.e.…”

Section: Main Textsupporting

confidence: 93%

“…These findings suggest a potential reason for enhanced transmissibility, though they did not account for potential confounders such as days since symptom onset at sampling. Many of these studies also use S gene target failure (SGTF) as a surrogate for the presence of B.1.1.7 ( 6 ) , which might misclassify samples, depending on the prevalence of B.1.1.7 ( 8 ) . Several analyses from community tested cases also suggest increased mortality associated with B.1.1.7 ( 8 ) .…”

Section: Main Textmentioning

confidence: 99%

“…Along with B.1.351, these variants of concern harbour functionally important mutations in the SARS-CoV-2 Spike protein, some of which demonstrate evidence of convergent evolution across all three lineages (Supplementary Table S1). Preliminary data ( 6, 7 ) shows that B.1.1.7 positive diagnostic respiratory samples may have lower cycle threshold (Ct) values, therefore higher viral loads, compared to other lineages. These findings suggest a potential reason for enhanced transmissibility, though they did not account for potential confounders such as days since symptom onset at sampling.…”

Section: Main Textmentioning

confidence: 99%

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Altered Subgenomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections

Parker

Lindsey

Shah

et al. 2021

Preprint

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SARS-CoV-2 lineage B.1.1.7 viruses are more transmissible, may lead to greater clinical severity, and result in modest reductions in antibody neutralization. subgenomic RNA (sgRNA) is produced by discontinuous transcription of the SARS-CoV-2 genome and is a crucial step in the SARS-CoV-2 life cycle. Applying our tool (periscope) to ARTIC Network Oxford Nanopore genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA expression profiles are significantly increased in B.1.1.7 infections (n=879). This increase is seen over the previous dominant circulating lineage in the UK, B.1.177 (n=943), which is independent of genomic reads, E gene cycle threshold and days since symptom onset at sampling. A noncanonical sgRNA which could represent ORF9b is found in 98.4% of B.1.1.7 SARS-CoV-2 infections compared with only 13.8% of other lineages, with a 16-fold increase in median expression. We hypothesise that this is a direct consequence of a triple nucleotide mutation in nucleocapsid (28280:GAT>CAT, D3L) creating a transcription regulatory-like sequence complementary to a region 3’ of the genomic leader. These findings provide a unique insight into the biology of B.1.1.7 and support monitoring of sgRNA profiles in sequence data to evaluate emerging potential variants of concern.One Sentence SummaryThe recently emerged and more transmissible SARS-CoV-2 lineage B.1.1.7 shows greater subgenomic RNA expression in clinical infections and enhanced expression of a noncanonical subgenomic RNA near ORF9b.

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Section: Main Textsupporting

confidence: 93%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

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Altered Subgenomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections

Parker

Lindsey

Shah

et al. 2021

Preprint

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“…As IFNs are critical in controlling early virus infection levels, IFN-resistant SARS-CoV-2 variants may produce higher viral loads that could in turn promote transmission and/or exacerbate pathogenesis. Consistent with this hypothesis, alarming preliminary reports linked B.1.1.7 with increased viral loads 34 and risk of death 35–37 . In addition to Spike, emerging variants exhibited mutations in nucleocapsid, membrane and nonstructural proteins NSP3, NSP6 and NSP12 (Supplementary Table 1).…”

Section: Discussionmentioning

confidence: 70%

Interferon Resistance of Emerging SARS-CoV-2 Variants

Guo

Barrett

Mickens

et al. 2021

Preprint

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The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity may drive the emergence of these novel variants, studies documenting a critical a role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against 5 viral lineages sampled during the course of the global outbreak that included ancestral and emerging variants. Our data revealed increased interferon resistance in emerging SARS-CoV-2 variants, indicating that evasion of innate immunity is a significant driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.

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“…They share the N501Y mutation in RBD besides the D614G mutation around the S1/S2 cleavage site (Table 2, Figure 6). Epidemiological studies suggest that the UK variant correlates with higher viral loads in patients [306], a >40% increased epidemiological growth [307,308], a longer duration of acute infection [309], and increased severity/death rate, particularly in patients of higher age and with comorbidities [310][311][312][313]. The UK variant acquired an enhanced affinity to ACE2 [314] while maintaining sensitivity to nAb responses though with 2-9 times reduced nAb titers in vaccinees and convalescent individuals [314][315][316].…”

Section: Sars-cov-2 Mutates On a Low But Constant Level Yielding Mutant Variants Over Timementioning

confidence: 99%

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

Duerr¹,

Jimenez²,

Dittmann³

2021

Preprint

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SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped, positive-stranded RNA viruses with envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.

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S-Variant SARS-CoV-2 Lineage B1.1.7 Is Associated With Significantly Higher Viral Load in Samples Tested by TaqPath Polymerase Chain Reaction

Cited by 222 publications

References 1 publication

Altered Subgenomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections

Altered Subgenomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections

Interferon Resistance of Emerging SARS-CoV-2 Variants

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

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