The appearance and spread of the SARS-CoV-2 Lambda variant (B.1.621)

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The global death toll from the 2019 coronavirus disease pandemic (COVID-19) is 4.43 million. Therefore, the need to maintain constant viral surveillance for the detection of emerging, possibly more pathogenic, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is paramount.

A new study details the genomic characteristics and decline of a variant of interest called B.1.621, which shows multiple amino acid substitutions within the Spike protein while discussing the impact of these variants on public health.

Study: Characterization of SARS-CoV-2 emerging interest variant B.1.621. Image credit: Cristian Moga / Shutterstock

Study: Characterization of the emerging interest variant B.1.621 of SARS-CoV-2. Image credit: Cristian Moga / Shutterstock

Background

Genetic diversification of SARS-CoV-2 may increase virus transmissibility and allow it to escape neutralization by antibodies generated in response to a natural infection or vaccination. During the first year of the pandemic, the clock-like molecular evolution pattern was observed in SARS-CoV-2.

From September 2020, substitutions began to be observed throughout the SARS-CoV-2 genome. Emerging variants of concern and those of interest (VOC and VOI, respectively) show mutations in the ear protein. This viral glycoprotein mediates viral adhesion to the angiotensin converting enzyme 2 (ACE2) receptor of the host cell. Therefore, ear protein is the primary target for neutralizing antibodies.

The B.1.621 lineage

The current study published in the journal Science reports on variant of interest B.1.621 on its polyclonal antibody neutralization efficiency, transmissibility, and binding affinity for ACE2.

The B.1 lineage appeared in Colombia between March and April 2021, marking a change in the lineage with multiple accumulated mutations. B.1.621, a member of this lineage, has the 146N insert, along with several substitutions such as I95I, 144T, and Y145S, all in the N-terminal domain; R346K, E484K, N501Y (all three in the receiver binding domain, RBD); and P681H (the latter at the S1 / S2 interface).

What did the study show?

Although routine monitoring of emerging variants was carried out in Colombia, in January 2021 it was strengthened to collect imported VOCs. By the end of the first week of May, more than 900 sequences had been uploaded to the GISAID database, the most common of which was the B.1 lineage, as they had been in circulation since the pandemic began.

B.1.621 showed an increase in frequency from January 2021 to fifth place in frequency. The current study included all genomes of this sequenced lineage until the end of April 2021.

Phylogenetic analyzes of this lineage suggested the descent of the B.1 lineage quite recently, and several codons of the Spike protein were positive selection signals. No recombination events were observed.

FIG. 2. Phylogeny and distribution of the SARS-CoV-2 variant b.1.621 in Colombia 2a) Phylogenetic tree of the new SARS-CoV-2 lineage leaving the B.1.621 lineage. The tree was most likely reconstructed with the estimated GTR + F + I + G4 nucleotide substitution model for the 434 genome dataset. The interactive tree can be accessed at the following link: https://microreact.org/project/5CAiK3qCMaEgE4vYkKVpZW/b7113efc 2b) Map of lineage distribution across the country.

FIG. 2. Phylogeny and distribution of the SARS-CoV-2 variant b.1.621 in Colombia 2a) Phylogenetic tree of the new SARS-CoV-2 lineage arising from the B.1.621 lineage. The tree was most likely reconstructed with the estimated GTR + F + I + G4 nucleotide substitution model for the 434 genome dataset. The interactive tree can be accessed at the following link: https://microreact.org/project/5CAiK3qCMaEgE4vYkKVpZW/b7113efc 2b) Map of lineage distribution across the country.

What are the implications?

The social fatigue of the pandemic patterns and the genetic characteristics of the B.1.621 strain itself caused changes in the transmissibility of this VOI. Its combat was aided by increased genomic surveillance of SARS-CoV-2 during the third wave of COVID-19 in the country.

Genomic sequencing is expected to cover 1% of all cases, allowing a better picture of the actual frequency of this lineage in Colombia and whether its domain increases or decreases.

The convergent substitutions seen in SARS-CoV-2 lineages worldwide are probably due to the high rate of genetic variability within the very high number of people not exposed worldwide, along with the use of antibodies. therapeutic monoclonal drugs that exert selection pressures on the viral genome.

Some of these common mutations are associated with relevant changes in function. E484K confers resistance to neutralization by convalescent plasma antibodies, in the presence of N501Y and suppression at 69/70 (del69 / 70). In contrast, 145N insertion is a new mutation, and its implications are unknown.

It is important to note that some of the substitutions of B.1.621 affect residues at locations targeted by the reverse transcriptase polymerase (RT PCR) chain reaction, possibly causing interference with test results and falsely increasing the number of cases that they are believed to be due to other VOCs.

This lineage has now been identified in Mexico, Curacao, the USA, Spain, the Netherlands, Denmark and Germany. An additional assessment of their biological and epidemiological contributions to the pandemic is required to assess the epidemiology of the lineage.

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