SARS-CoV-2 variant Delta rapidly displaced variant Alpha in the United States and led to higher viral loads

Bolze, Alexandre; Luo, Shishi; White, Simon; Cirulli, Elizabeth T.; Wyman, Dana; Rossi, Andrew Dei; Machado, Henrique; Cassens, Tyler; Jacobs, Sharoni; Barrett, Kelly; Tanudjaja, Francisco; Tsan, Kevin; Nguyen, Jason; Ramirez, Jimmy M.; Sandoval, Efren; Wang, Xueqing; Wong, David; Becker, David G.; Laurent, Marc; Lu, James T.; Isaksson, Magnus; Washington, Nicole; Lee, William

doi:10.1016/j.xcrm.2022.100564

Cited by 75 publications

(66 citation statements)

References 22 publications

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“…Recently, studies comparing the entry rate of PVs packaged with various SARS-CoV-2 spike variants into target cells showed that PVs bearing the Delta spike (Delta PVs) drove markedly faster initial infection, and greater infection overall, than other variants [ 35 , 43 ]. This phenotype is similar to real-world reports of faster initial infection by Delta SARS-CoV-2 [ 37 ].…”

Section: Introductionsupporting

confidence: 88%

“…The Alpha variant prevailed until it was outcompeted by the VOC Delta (lineage B.1.617.2), a member of the B.1.617 lineage, that arose in India and became globally dominant in mid-2021 [ 33 ]. The Delta variant was considerably more transmissible than Alpha [ 34 ], infected individuals faster, produced earlier detection by PCR test with higher viral load [ 35 , 36 , 37 ], and was more pathogenic [ 38 ]. The Delta variant’s spike displayed a different combination of mutations compared to Alpha, that were predicted to reduce sensitivity to neutralizing antibodies [ 39 , 40 , 41 ] and increase ACE2 receptor binding, spike stability, viral infectivity, fusogenicity, and pathogenicity [ 42 , 43 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

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Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein

Petersen

Lü

Fitzgerald

et al. 2022

Viruses

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Individuals infected with the SARS-CoV-2 Delta variant, lineage B.1.617.2, exhibit faster initial infection with a higher viral load than prior variants, and pseudotyped viral particles bearing the SARS-CoV-2 Delta variant spike protein induce a faster initial infection rate of target cells compared to those bearing other SARS-CoV-2 variant spikes. Here, we show that pseudotyped viral particles bearing the Delta variant spike form unique aggregates, as evidenced by negative stain and cryogenic electron microscopy (EM), flow cytometry, and nanoparticle tracking analysis. Viral particles pseudotyped with other SARS-CoV-2 spike variants do not show aggregation by any of these criteria. The contribution to infection kinetics of the Delta spike’s unique property to aggregate is discussed with respect to recent evidence for collective infection by other viruses. Irrespective of this intriguing possibility, spike-dependent aggregation is a new functional parameter of spike-expressing viral particles to evaluate in future spike protein variants.

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Section: Introductionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein

Petersen

Lü

Fitzgerald

et al. 2022

Viruses

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“…Although travel restrictions, quarantine and vaccination measures were implemented worldwide, Delta rapidly established itself as the dominant variant in countries like India, the UK, the Netherlands and Australia, (Campbell et al, 2021; Wintersdorff et al, 2021) and displaced Alpha in the US by July 2021 (Bolze et al, 2021). Alpha was the dominant VOC detected in our samples from March to June (Figs.…”

Section: Resultsmentioning

confidence: 99%

“…To date, there have been numerous studies assessing the spread of SARS-CoV-2 and the emergence of new variants internationally, such as in the US and the UK (Bolze et al, 2021; Martin et al, 2021; Volz et al, 2021a, 2021b), but few studies from Japan have examined the recent domestic rapid evolution and variant predominance in detail. We performed next-generation sequencing (NGS) of positive cases of SARS-CoV-2 detected by RT-PCR at the Genesis Institute of Genetic Research, and carried out lineage assessment to detect trends in variant predominance and their correlation with RT-PCR results.…”

Section: Introductionmentioning

confidence: 99%

Rapid displacement of SARS-CoV-2 variants within Japan correlates with cycle threshold values on routine RT-PCR testing

Wright

Chan

Chaochaisit

et al. 2022

Preprint

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Background: The rapid spread of SARS-CoV-2 worldwide has led to the emergence of new variants due to the presence of mutations that alter viral characteristics, but there have been few studies on trends in viral lineages in Japan, an island country. We hypothesized that changes in cycle threshold (Ct) values on reverse transcription polymerase chain reaction (RT-PCR) reflect the prevalent variants during a given period. Methods: We performed next-generation sequencing of positive samples to identify the viral lineages in Japan in 2021 and compared variant prevalence with the average Ct values on routine RT-PCR using 4 primer sets. Results: Based on 3 sequencing runs, the highly transmissible Alpha variant, which prevailed over other lineages, such as R.1, from April 2021, was dominated by the even stronger Delta variant between July and August 2021 in Japan. The decrease in our routine RT-PCR Ct values with 4 primer sets correlated with these fluctuations in lineage prevalence over time. Conclusions: We confirmed that our RT-PCR protocol reflects the trends in SARS-CoV-2 variant prevalence over time regardless of sequence mutation. This may aid in the tracking of new variants in the population.

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“…In particular, mutations in RBD that retain its structural integrity and function (ACE2-binding) may escape neutralizing antibodies by altering the binding surface either in composition or in conformation, or both (Weisblum et al, 2020 ; Harvey et al, 2021 ; Liu et al, 2021 ; Starr et al, 2021 ). In the past months, strains, such as the lineage B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.1.529, referred to as the Alpha, Beta, Gamma, Delta, and Omicron variant by the World Health Organization, have caused outbreaks and concerns about how these variants, the Omicron in particular (Viana et al, 2022 ), could change the course of the pandemic due to their high virulence and their general resistance against antibodies and vaccines that were developed using previous strains (Hoffmann et al, 2021 ; Planas et al, 2021 ; Wang et al, 2021 ; Bolze et al, 2022 ). Given the large number of active cases, it is reasonable to assume that more escape mutants are almost certain to emerge.…”

Section: Introductionmentioning

confidence: 99%

Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants

Zhou

Luo

et al. 2022

Front. Microbiol.

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SARS-CoV-2 and its variants, such as the Omicron continue to threaten public health. The virus recognizes the host cell by attaching its Spike (S) receptor-binding domain (RBD) to the host receptor, ACE2. Therefore, RBD is a primary target for neutralizing antibodies and vaccines. Here, we report the isolation and biological and structural characterization of a single-chain antibody (nanobody) from RBD-immunized alpaca. The nanobody, named DL28, binds to RBD tightly with a KD of 1.56 nM and neutralizes the original SARS-CoV-2 strain with an IC50 of 0.41 μg mL−1. Neutralization assays with a panel of variants of concern (VOCs) reveal its wide-spectrum activity with IC50 values ranging from 0.35 to 1.66 μg mL−1 for the Alpha/Beta/Gamma/Delta and an IC50 of 0.66 μg mL−1 for the currently prevalent Omicron. Competition binding assays show that DL28 blocks ACE2-binding. However, structural characterizations and mutagenesis suggest that unlike most antibodies, the blockage by DL28 does not involve direct competition or steric hindrance. Rather, DL28 may use a “conformation competition” mechanism where it excludes ACE2 by keeping an RBD loop in a conformation incompatible with ACE2-binding.

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SARS-CoV-2 variant Delta rapidly displaced variant Alpha in the United States and led to higher viral loads

Cited by 75 publications

References 22 publications

Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein

Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein

Rapid displacement of SARS-CoV-2 variants within Japan correlates with cycle threshold values on routine RT-PCR testing

Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants

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