Lambda lineage of SARS-CoV-2 has potential to become variant of concern

Researchers have described the first reported infection with the C.37 (Lambda) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Southern Brazil.

The SARS-CoV-2 virus is the agent responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. The Lambda lineage was classified as a variant of interest (VOI) by the World Health Organization on June 15th, 2021.

The C.37 variant, which lies within the B.1.1.1 lineage, has already been reported as highly prevalent in Peru and has also been identified in many countries across the Americas, Europe and Oceania, says Priscila Wink from the Hospital de Clínicas de Porto Alegre in Rio Grande do Sul and colleagues.

However, C.37 has only been reported occasionally in Brazil despite its global spread, adds the team.

Now, Wink and colleagues have described the first case of C.37 infection in Southern Brazil. The researchers discovered eight defining mutations in the variant, in addition to the 19 mutations that have already been described for other members of this lineage.

“Considering that this VOI has been associated with high rates of transmissibility, the possible spread in the Southern Brazilian community is a matter of concern,” they write.

A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.

Emerging variants threaten the efficacy of COVID-19 control strategies

Since SARS-CoV-2 was first identified in late December 2019, new VOIs and variants of concern (VOCs) have emerged with potentially increased transmissibility and reduced sensitivity to antibody neutralization following infection or vaccination.

The emergence of these lineages may impact the efficacy of strategies to control the COVID-19 pandemic.

The novel Lambda variant was detected in Peru in August 2020 and has been identified in 26 other countries, says Wink and colleagues.

“However, despite global spread of the Lambda variant, in Brazil this lineage was reported only in São Paulo state in February 2021,” they write.

What did the researchers do?

Now, the team has described the first reported case of the SARS-CoV-2 Lambda variant in Southern Brazil.

A young male who had visited Argentina developed respiratory symptoms while returning to his hometown in Rio Grande do Sul, the southernmost Brazilian state.

He was admitted to a local hospital two days later but was then transferred to the intensive care unit of Hospital de Clínicas de Porto Alegre a further two days later due to worsening symptoms.

Infection with SARS-CoV-2 was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) testing of nasopharyngeal swabs and a specimen was submitted for whole-genome sequencing.

What did they find?

Sequencing of the resulting genomic libraries revealed that the C.37 variant is defined by a deletion (Δ3675- 3677) in open reading frame 1a (ORF1a) of SARS-CoV-2. The ORF1a gene codes for a protein that undergoes proteolytic cleavage before it goes on to make nonstructural viral proteins.

The deletion has also been identified in the Alpha (B.1.1.7) variant that emerged in the UK, the Beta (B.1.351) variant that emerged in South African, and the Gamma (P.1) variant that emerged in Brazil.

The Lambda variant also contained a novel deletion (Δ246-252) and multiple nonsynonymous mutations (G75V, T76I, L452Q, F490S, D614G, and T859N) in the gene that encodes the viral spike protein. The spike is the main surface structure the virus uses to bind to and infect host cells.

The mutations L452Q and F490S are present in the spike receptor-binding domain (RBD), which mediates the initial stage of infection by binding to the host cell receptor angiotensin-converting enzyme 2 (ACE2).

The F490S mutation has previously been associated with reduced susceptibility to antibody neutralization, says Wink and colleagues.

The researchers say that in addition to these eight C.37-defining mutations, 19 mutations were also present that have already been described in other members of the lineage.

The team expects that C.37 will become a variant of concern

The team says the high prevalence of this new VOI has already been described in Chile, Peru, Ecuador, and Argentina, where it is associated with substantial rates of community transmission.

“It is believed that the critical health care system situation and the recent report of increased deaths in these countries is associated with the rising prevalence of the Lambda variant,” writes Wink and colleagues.

The researchers say that it is not yet known whether this variant is more transmissible or more pathogenic than other variants or whether it is able to escape vaccine-induced immunity.

“The novel S: Δ246-252 deletion and additional mutations in the spike protein should be taken into account to understand their effects on viral fitness and host interaction,” they say.

“Considering that this VOI has rapidly spread in Peru, Ecuador, Chile, and Argentina, we believe that it has considerable potential to become a variant of concern,” concludes the team.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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