The emergence and spread of the SARS-Cov-2 Lambda variant (B.1.621)

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

New study details genomic and progeny characteristics 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 health public.

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

Background

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

From September 2020, substitutions began to be observed across the entire SARS-CoV-2 genome. Emerging variants of concern and variants of interest (COV and VOI, respectively) exhibit mutations in the spike protein. This viral glycoprotein mediates viral binding to the angiotensin-converting enzyme 2 (ACE2) receptor of the host cell. Thus, the spike protein is the main target of neutralizing antibodies.

Line B.1.621

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

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

What did the study show?

While routine surveillance was carried out in Colombia for emerging variants, in January 2021 it was stepped up to recover 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 lineage B.1, in circulation since the pandemic took hold.

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

Phylogenetic analyzes of this line suggested the progeny of the B.1 line quite recently, and several codons of the Spike protein were signals of positive selection. No recombination event was observed.

Fig. 2. Phylogeny and distribution of the SARS-CoV-2 b.1.621 variant in Colombia 2a) Phylogenetic tree of the new line of SARS-CoV-2 derived from the B.1.621 line. The tree was reconstructed by maximum likelihood with the estimated model of nucleotide substitution GTR + F + I + G4 for the dataset of 434 genomes. The interactive tree is accessible via the following link: https://microreact.org/project/5CAiK3qCMaEgE4vYkKVpZW/b7113efc 2b) Lineage distribution map across the country.

What are the implications?

Social weariness with pandemic guidelines and the genetic characteristics of the B.1.621 strain itself have led to changes in the transmissibility of this VOI. Whose fight was aided by increased genomic surveillance for SARS-CoV-2 during the third wave of COVID-19 in the country.

Genomic sequencing should cover one percent of all cases, allowing a better picture of the true frequency of this lineage in Colombia and whether its dominance is increasing or decreasing.

The convergent substitutions observed in SARS-CoV-2 lines worldwide are probably due to the high rate of genetic variability within the very high number of unexposed individuals worldwide, coupled with the use of therapeutic monoclonal antibodies that exert selection pressures on the viral genome.

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

It is important to note that some of the substitutions in B.1.621 affect residues at locations targeted by the reverse transcriptase polymerase chain reaction (RT PCR), which can interfere with test results and increase to incorrectly the number of cases considered to be due to other VOCs.

This line has now been identified in Mexico, Curaçao, the United States, Spain, the Netherlands, Denmark and Germany. Further evaluation of its biological and epidemiological contributions to the pandemic is needed to assess the epidemiology of the lineage.