Lambda lineage of SARS-CoV-2 has potential to become a 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-CoV2 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 Pricila Wink from the Hospital de Clinicas de Porto Alegre in Rio Frande do Sul and colleagues.
• However, C.37 has only been reported occassionally in Brazil despite its global spread, adds the team.
• Now, Wink and colleagues have described the first case of C.37 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.

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 transmissability 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.

What did the researchers do?

• Now, the team has described the first reported case of the SARS-CoV02 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 transfered to the intensive care unit of Hospital de Clinicas 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 a deletion (3675-3677) 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 Southern Africa, and the Gamma (P.1) variant that emerged in Brazil.
• The Lambda variant also contained a novel deletion (246-252) and multiple nonsynonymous mutations (G75V, T761, 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 intial 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.
• The researchers say that it is not yet known whether this variant is more transmissable or more pathogenic than other variants or whether it is able to escape vaccine-induced immunity.