key: cord-0291004-vplxp3sa authors: Romero, P. E.; Davila-Barclay, A.; Salvatierra, G.; Gonzalez, L.; Cuicapuza, D.; Solis, L.; Marcos-Carbajal, P.; Huancachoque, J.; Maturrano, L.; Tsukayama, P. title: The Emergence of SARS-CoV-2 Variant Lambda (C.37) in South America date: 2021-07-03 journal: nan DOI: 10.1101/2021.06.26.21259487 sha: 10d2fa9e21f989457d12be529a691bf8dbfa54b2 doc_id: 291004 cord_uid: vplxp3sa We report the emergence of a novel lineage of SARS-CoV-2 in South America, termed C.37. It presents a deletion in the ORF1a gene ({Delta}3675-3677), also found in variants of concern (VOCs) Alpha, Beta, and Gamma, and seven non-synonymous mutations in the Spike gene ({Delta}247-253, G75V, T76I, L452Q, F490S, T859N). Initially reported in Lima, Peru, in late December 2020, it now accounts for almost 100% of Peruvian genomes in April 2021. It is expanding in Chile and Argentina, and there is evidence of onward transmission in Colombia, Mexico, the USA, Germany, and Israel. On June 15, 2021, the World Health Organization designated C.37 as Variant of Interest (VOI) Lambda. Peru has been severely hit by the COVID-19 pandemic: As of May 31, 2021, it had the highest rate of COVID-19 deaths globally relative to its population (180764 out of 33.38 million: ~0.54% of the country's population) (2) . By June 2021, 1424 genome sequences from Peru were available on GISAID, comprising 64 circulating PANGO lineages (3) . Routine genomic surveillance in early 2021 revealed a deep-branching sublineage of B.1.1.1, now classified as C.37 ( Figure 1) . It was first reported in Lima in December 2020 (1 of 192 genomes, 0.5%), expanding to 20.5%, 36.4%, 79.2%, and 96.6% in January, February, March, and April 2021, respectively ( Figure 2 ). In contrast, Variants of Concern were detected less frequently over these four months in Peru: Alpha, n=7, 0.5%; Gamma, n=17, 1.2% ( Figure 1 ). C.37 contains a novel deletion (S:Δ247-253, located at the N-terminal domain) and six nonsynonymous mutations in the Spike gene (G75V, T76I, D614G, L452Q, F490S, T859N) ( and is associated with increased affinity for the ACE2 receptor (4). F490S has been associated with reduced in vitro susceptibility to antibody neutralization (5,6). C.37 also displays the ORF1a:Δ3675-3677 deletion, found in VOCs Alpha, Beta, and Gamma (7). The earliest record of C.37 on GISAID is from Argentina in November 2020. By June 19, 2021, there were 1771 C.37 sequences from 25 countries, including Chile (n=670), USA (n=510), Peru (n=222), Argentina (n=86), Germany (n=79), Mexico (n=55), Spain (n=40), and Ecuador (n=39). Beyond Peru, C.37 has expanded rapidly in Chile and Argentina, reaching 33% and 12% of all sequenced genomes on GISAID by April 2021, respectively ( Figure 2 ). The emergence of this lineage in Peru and its export to other countries is a current hypothesis, given its earlier detection and rise to nearly 100% of public sequences by April. We are sequencing additional Peruvian samples from October to December 2020 to confirm and date the origin of C.37. Expansion of C.37 has occurred in South America in the presence of hundreds of circulating lineages and VOCs Alpha and Gamma ( Figure 1B) , suggesting increased transmissibility of this lineage. However, additional epidemiological data and analyses are needed to assess its transmission, virulence, and immune escape properties. On June 15, 2021, the World Health Organization designated C.37 as VOI Lambda (8). All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 3, 2021. ; https://doi.org/10.1101/2021.06.26.21259487 doi: medRxiv preprint Peruvian genomes were generated at Universidad Peruana Cayetano Heredia and Instituto Nacional de Salud using the Illumina COVIDseq or the Qiagen SARS-Cov-2 panel and QIAseq FX DNA library kits. Libraries were sequenced on Illumina MiSeq and NextSeq 550 instruments. Reads were processed and assembled with the Illumina DRAGEN COVID pipeline or a custom pipeline based on MEGAHIT v1.2.9. Assemblies with an average base coverage higher than 1000x were submitted to GISAID. We downloaded SARS-CoV-2 genome assemblies from Argentina (n=2229), Chile (n=2564), and Peru (n=1424), available in GISAID by June 2021. Sequences were processed using the Nextstrain augur pipeline (9) . Genomes were aligned against the Wuhan reference genome (NC_045512.2) using MAFFT v7.48. We then built a maximum likelihood phylogeny using IQTREE v.2.1.4. The tree was calibrated under a general time-reversible (GTR) model of nucleotide substitution, assuming a clock rate of 8×10 −4 . Two genomes from China (EPI_ISL_402123, EPI_ISL_406798) were used as the outgroup. All analyzed sequences were publicly available in GISAID at the time of manuscript submission. Raw Illumina reads from 350 Peruvian genomes sequenced at UPCH are available at NCBI BioProject PRJNA667090. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Gene Amino acid N P13L, R203K, G204R, G214C, T366I ORF1a T1246I, P2287S, F2387V, L3201P, T3255I, G3278S, (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 3, 2021. ; https://doi.org/10.1101/2021.06.26.21259487 doi: medRxiv preprint Public health actions to control new SARS-CoV-2 variants Criterios técnicos para actualizar la cifra de fallecidos por COVID-19 en Perú Genomic epidemiology of SARS-CoV-2 in Peru Mutations Strengthened SARS-CoV-2 Infectivity Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization COVID-19 Weekly Epidemiological Update Augur: a bioinformatics toolkit for phylogenetic analyses of human pathogens The Institutional Review Board of Universidad Peruana Cayetano Heredia approved the project in June 2020 (E051-12-20).. We are funded by Fondo Nacional de Ciencia y Tecnología (FONDECYT) grants #046-2020, #022-2021, and Universidad Nacional Mayor de San Marcos grant #A2008007M. PER is supported by FONDECYT grant #034-2019. We thank our collaborators at Instituto Nacional de Salud for providing clinical specimens for sequencing. We acknowledge colleagues in the laboratories that generated and shared genetic sequence data via the GISAID Initiative, on which this study is based.