The localized rise of a B.1.526 SARS-CoV-2 variant containing an E484K mutation in New York State

Lasek‐Nesselquist, Erica; Lapierre, Pascal; Schneider, Erasmus; Ks, George; Pata, Janice D.

doi:10.1101/2021.02.26.21251868

Cited by 35 publications

(44 citation statements)

References 25 publications

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“…The recently identified B.1.526 variant SARS-CoV-2 appears to be increasing in prevalence in New York City raising concerns about reinfection and immunoevasion [14][15][16]. We report here that both S477N and E484K versions of B.1.526 were neutralized well by convalescent and vaccine-elicited antibodies.…”

Section: Discussionmentioning

confidence: 64%

“…Recent reports have identified a novel variant in New York City termed B.1.526 that was rapidly spreading [14][15][16]. The variant was identified in November, 2020; by January, 2021 the variant accounted for 5% of genomes sequenced from individuals in New York and by mid-February was detected with a frequency of 12.3% [14][15][16]. The variant contains several mutations in the spike protein, some of which have not been found in previous variants.…”

Section: Introductionmentioning

confidence: 99%

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B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

Zhou

Dcosta

Samanovic

et al. 2021

Preprint

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DNA sequence analysis recently identified the novel SARS-CoV-2 variant B.1.526 that is spreading at an alarming rate in the New York City area. Two versions of the variant were identified, both with the prevalent D614G mutation in the spike protein together with four novel point mutations and with an E484K or S477N mutation in the receptor binding domain, raising concerns of possible resistance to vaccine-elicited and therapeutic antibodies. We report that convalescent sera and vaccine-elicited antibodies retain full neutralizing titer against the S477N B.1.526 variant and neutralize the E484K version with a modest 3.5-fold decrease in titer as compared to D614G. The E484K version was neutralized with a 12-fold decrease in titer by the REGN10933 monoclonal antibody but the combination cocktail with REGN10987 was fully active. The findings suggest that current vaccines and therapeutic monoclonal antibodies will remain protective against the B.1.526 variants. The findings further support the value of wide-spread vaccination.

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Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

Zhou

Dcosta

Samanovic

et al. 2021

Preprint

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“…Of the samples with spike target failure, 87.2% (41/47) were B.1.375 and 12.8% (6/47) were other lineages. Thus, if we used ORF1a target failure (with or without spike target failure) to identify high priority samples for sequencing, we would have confirmed 100% of the B.1.1.7 samples and detected two new variants of interest (B.1.525 and B.1.526, both containing the E484K mutation) 18 while triaging 74% (207/305) of the samples.…”

Section: Mainmentioning

confidence: 98%

“…Moreover, we detected other virus lineages with double target failure (notably B.1.525) and ORF1a target failure (notably B.1.526), which are not currently variants of concern. B.1.525 and B.1.526, however, are of interest as they do contain the E484K and other key spike mutations that require further evaluation of their implications for transmissibility and immune escape 18 . These examples demonstrate that continuous monitoring of the lineages that contain the ORF1a Δ3675-3677 and spike Δ69-70 deletions will be necessary to ensure the local effectiveness of our assay.…”

Section: Mainmentioning

confidence: 99%

PCR assay to enhance global surveillance for SARS-CoV-2 variants of concern

Vogels

Breban

Alpert

et al. 2021

Preprint

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With the emergence of SARS-CoV-2 variants that may increase transmissibility and/or cause escape from immune responses1–3, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant first detected in the UK4,5 could be serendipitously detected by the ThermoFisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69-70, would cause a “spike gene target failure” (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern that lack spike Δ69-70, such as B.1.351 (also 501Y.V2) detected in South Africa6 and P.1 (also 501Y.V3) recently detected in Brazil7. We identified a deletion in the ORF1a gene (ORF1a Δ3675-3677) in all three variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675-3677 as the primary target and spike Δ69-70 to differentiate, we designed and validated an open source PCR assay to detect SARS-CoV-2 variants of concern8. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence spread of B.1.1.7, B.1.351, and P.1.

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“…The most recent report found that the E484K has been successfully incorporated into some isolates of the B.1.1.7 variant [8]. Moreover, the new variant of interest discovered in New York (B.1.526) also carries the E484K mutation, and alarmingly, fast-spreading over the past two months [9, 10]. Another key spike mutation, N501Y, present in all three VOCs is considered to enhance the binding between spike and the ACE2 receptor in human cells, thus contributing to increased transmissibility and possibly virulence as well [11, 12, 13].…”

mentioning

confidence: 99%

A Novel Diagnostic Test to Screen SARS-CoV-2 Variants Containing E484K and N501Y Mutations

Zhao

Lee

Composto

et al. 2021

Preprint

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Spike protein mutations E484K and N501Y carried by SARS-CoV-2 variants have been associated with concerning changes of the virus, including resistance to neutralizing antibodies and increased transmissibility. While the concerning variants are fast spreading in various geographical areas, identification and monitoring of these variants is lagging far behind, due in large part to the slow speed and insufficient capacity of viral sequencing. In response to the unmet need for a fast and efficient screening tool, we developed a single-tube duplex molecular assay for rapid and simultaneous identification of E484K and N501Y mutations from nasopharyngeal swab (NS) samples within 2.5 h from sample preparation to report. Using this tool, we screened a total of 435 clinical NS samples collected from COVID patients at 8 hospitals within the Hackensack Meridian Health network in New Jersey. While B.1.351 and P.1 variants were absent from the current study, our data revealed a dramatic increase in the frequency of E484K over time, underscoring the need for continuous epidemiological monitoring.

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The localized rise of a B.1.526 SARS-CoV-2 variant containing an E484K mutation in New York State

Cited by 35 publications

References 25 publications

B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

PCR assay to enhance global surveillance for SARS-CoV-2 variants of concern

A Novel Diagnostic Test to Screen SARS-CoV-2 Variants Containing E484K and N501Y Mutations

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