Emergence of the E484K Mutation in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Lineage B.1.1.345 in Upstate New York
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Abstract
A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.345 variant carrying the E484K mutation was detected in 4 patients with no apparent epidemiological association from a hospital network in upstate New York. Subsequent analysis identified an additional 11 B.1.1.345 variants from this region between December 2020 and February 2021.
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Our take
This study, available as a preprint and thus not yet peer-reviewed, described the identification of a new SARS-Cov-2 variant (B.1.220 with the E484K mutation) in Upstate New York in early 2021. The E484K mutation has been identified in other variants of concern, including 501Y.V2/B.1.351 identified first in South Africa, and P.1. identified first in Brazil. Some studies suggest that this mutation may lead to reduced vaccine efficacy as well as antibody-based treatment and prevention of COVID-19; recent clinical data indicate that the Pfizer, Moderna, and J&J vaccines are still protective against other variants with the E484K mutation. The independent emergence of E484K in different SARS-CoV-2 variant backgrounds is concerning, as it implies that this mutation provides a fitness advantage to the virus, even in the …
Our take
This study, available as a preprint and thus not yet peer-reviewed, described the identification of a new SARS-Cov-2 variant (B.1.220 with the E484K mutation) in Upstate New York in early 2021. The E484K mutation has been identified in other variants of concern, including 501Y.V2/B.1.351 identified first in South Africa, and P.1. identified first in Brazil. Some studies suggest that this mutation may lead to reduced vaccine efficacy as well as antibody-based treatment and prevention of COVID-19; recent clinical data indicate that the Pfizer, Moderna, and J&J vaccines are still protective against other variants with the E484K mutation. The independent emergence of E484K in different SARS-CoV-2 variant backgrounds is concerning, as it implies that this mutation provides a fitness advantage to the virus, even in the context of increasing vaccine coverage. This study illustrates the key role of genomic surveillance in the early identification of new SARS-CoV-2 variants, which is important for limiting their spread.
Study design
retrospective-cohort
Study population and setting
This study described the identification of a SARS-CoV-2 B.1.220 variant carrying the E484K mutation in the Finger Lakes region of New York. The E484K mutation in the spike protein, which is present in other variants of concern (501Y.V2/B.1.351, P.1, and B.1.526), may lead to immune escape due to reduced antibody neutralization activity. Since June 2020, SARS-CoV-2-positive samples from the Rochester Regional Health System have been sent to the Multidrug-Resistant Organism Repository and Surveillance Network (MRSN) for whole genome sequencing as part of a joint surveillance effort. This study included sequences collected at five hospitals in Upstate New York between January 27, and February 7, 2021 (n=20); additional sequences of interest were identified using the Microreact and GISAID databases (n=12). B.1.220 variant sequences with the E484K mutation (n=17) were used for phylogenetic analysis and single nucleotide polymorphism-based comparisons.
Summary of main findings
The E484K mutation was identified in five sequences from four unique patients (one male, three females; mean age of 85 years; all recovered) with no evidence of epidemiologic linkage. All five sequences were assigned to the B.1.220 lineage and had additional lineage-defining mutations (R203K, G204R, P314L and D614G). The samples collected from the same patient were genetically identical. The Microreact and GISAID databases contained 12 additional B.1.220 variant sequences with the E484K mutation collected from six different New York counties between December 2020 and February 2021. Phylogenetic analysis suggested that the E484K mutation arose in at least two independent events within this sample set. At the time of submission, no B.1.1.220 variants with the E484K mutation had been identified outside of New York.
Study strengths
Routine genomic surveillance with whole genome sequencing was used to identify a new SARS-CoV-2 variant with a mutation of known concern for immune escape.
Limitations
The sample size in this study was quite small (n=20); phylogenetic analysis was based on only 16 unique variant sequences, 12 of which were identified using database searches. Additional sequences are needed to better assess the emergence and transmission dynamics of this potential variant of concern. No experiments were presented assessing the functional impact of the E484K mutation (in the context of the B.1.220 genetic background) on the efficacy of vaccines or antibody-based treatments.
Value added
This study describes the emergence of a new SARS-CoV-2 B.1.220 variant with the E484K mutation, identified by whole genome sequencing as part of an ongoing genetic surveillance project. When present in other variants of concern, this mutation has been implicated in immune escape.
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SciScore for 10.1101/2021.03.11.21253231: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Bioinformatic Analysis of SARS-CoV-2 genomes: Miseq read data was trimmed for adapters and low quality sequence using BBduk v38.79 (https://sourceforge.net/projects/bbmap/). Miseqsuggested: (A5-miseq, RRID:SCR_012148)Nucleotide alignments were performed with Muscle23 followed by trimming of ambiguous/under-represented sequence at the 5’/3’ ends of the alignment in Geneious. Geneioussuggested: (Geneious, RRID:SCR_010519)Results from OddPub: Thank you for sharing your code.
Results …SciScore for 10.1101/2021.03.11.21253231: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Bioinformatic Analysis of SARS-CoV-2 genomes: Miseq read data was trimmed for adapters and low quality sequence using BBduk v38.79 (https://sourceforge.net/projects/bbmap/). Miseqsuggested: (A5-miseq, RRID:SCR_012148)Nucleotide alignments were performed with Muscle23 followed by trimming of ambiguous/under-represented sequence at the 5’/3’ ends of the alignment in Geneious. Geneioussuggested: (Geneious, RRID:SCR_010519)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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