SARS-CoV-2 Genomic Surveillance in Costa Rica: Evidence of a Divergent Population and an Increased Detection of a Spike T1117I Mutation

Abstract

Genome sequencing is a key strategy in the surveillance of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Latin America is the hardest hit region of the world, accumulating almost 20% of COVID-19 cases worldwide. Costa Rica was first exemplary for the region in its pandemic control, declaring a swift state of emergency on March 16th that led to a low quantity of cases, until measures were lifted in early May. From the first detected case in March 6th to December 31st almost 170 000 cases have been reported in Costa Rica, 99.5% of them from May onwards. We analyzed the genomic variability during the SARS-CoV-2 pandemic in Costa Rica using 185 sequences, 52 from the first months of the pandemic, and 133 from the current wave.Three GISAID clades (G, GH, and GR) and three PANGOLIN lineages (B.1, B.1.1, and B.1.291) are predominant, with phylogenetic relationships that are in line with the results of other Latin American countries, suggesting introduction and multiple re-introductions from other regions of the world. The whole-genome variant calling analysis identified a total of 283 distinct nucleotide variants. These correspond mostly to non-synonymous mutations (51.6%, 146) but 45.6% (129) corresponded to synonymous mutations. The 283 variants showed an expected power-law distribution: 190 single nucleotide mutations were identified in single sequences, only 16 single nucleotide mutations were found in >5% sequences, and only two mutations in >50% genomes. These mutations were distributed through the whole genome. However, 63.6% were present in ORF1ab, 11.7% in Spike gene and 10.6% in the Nucleocapsid gene. Additionally, the prevalence of worldwide-found variant D614G in the Spike (98.9% in Costa Rica), ORF8 L84S (1.1%) is similar to what is found elsewhere. Interestingly, the frequency of mutation T1117I in the Spike has increased during the current pandemic wave beginning in May 2020 in Costa Rica, reaching 29.2% detection in the full genome analyses in November 2020. This variant has been observed in less than 1% of the GISAID reported sequences worldwide in all the 2020. Structural modeling of the Spike protein with the T1117I mutation suggest a potential effect on the viral oligomerization needed for cell infection, but no differences with other genomes on transmissibility, severity nor vaccine effectiveness are predicted. Nevertheless, in-vitro experiments are required to support these in-silico findings. In conclusion, genome analyses of the SARS-CoV-2 sequences over the course of COVID-19 pandemic in Costa Rica suggest introduction of lineages from other countries as travel bans and measures were lifted, similar to results found in other studies, as well as an increase in the Spike-T1117I variant that needs to be monitored and studied in further analyses as part of the surveillance program during the pandemic.

Detection of SARS-CoV-2 spike protein D614G mutation by qPCR-HRM analysis

“…Surveillance for the D614G mutation is important because the variant that contains this mutation, or the G614 variant, is more transmissible and has become the dominant variant of SARS-CoV-2 that has been circulated around the world, including Indonesia 5 , 6 . Compare with other countries like Costa Rika, which was dominated by the G614 variant by 98.9%, the prevalence of the G614 variant detected in Indonesia was only 65% in September 2020 5 , 29 . In addition, all variants of concerns (VOCs) of SARS-CoV-2, which are considered to be more transmissible, pathogenic, and immune-resistant, were generated from the G614 variant lineage 30 , 31 , 32 , 33 .…”

Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein

“…The A.2.5 lineage likely spread very early also in the neighboring countries, with evidence of multiple introductions. While early investigations failed to identify A.2.5 in Costa Rica in August 2020 (Molina-Mora et al, 2020), the prevalence of this lineage may have reached 30% between March and June 2021, with evidence of multiple introductions and the establishment of large clusters of community transmission, such as the one characterizing the A.2.5.1 sublineage ( Figure 4 ).…”

“…Interestingly, A.2.5 has been linked with clinically documented reinfections in individuals previously infected by the A.2.4 lineage, which is consistent with the presence of the constellation of non-synonymous spike mutations reported in the previous section, some of which may have immune escape properties (Díaz et al, 2021). The A.2.5 lineage likely spread very early also in the neighboring countries: while investigations carried out in August 2020 failed to identify A.2.5 in Costa Rica (Molina-Mora et al, 2021), the prevalence of this lineage in the country reached 30% between March and June 2021, with the establishment of large clusters of community transmission ( Figure 4 ). A.2.5 may have undergone a similar spread in other countries in central America, including Belize, Honduras, El Salvador, Guatemala and Mexico, where multiple cases have been detected, starting from the spring of 2021 ( Figure 4 ).…”

Overview of the SARS-CoV-2 genotypes circulating in Latin America during 2021

“…The World Health Organization (WHO) has classified five divergent genotypes as variants of concern (VOC: Alpha, Beta, Gamma, Delta, Omicron), as well as some lineages into variants of interest (VOI: Lambda, Mu, Epsilon, Zeta, Theta, Iota, Eta, Kappa, and others) and variants under monitoring (VUM: B.1.640 and XD) (World Health Organization, 2022). All the reported variants and other lineages have been identified in Latin America (Pan American Health Organization, 2021), including genotypes that were first reported regionally, such as Gamma in Brazil, Mu in Colombia, and Lambda in Peru (World Health Organization, 2022), as well as unique lineages in Costa Rica and Central America (Molina-Mora, 2022; Molina-Mora et al, 2021). Those descriptions of locally enriched genotypes exemplify the opportunities that SARS-CoV-2 has found in Latin America for spreading and evolving.…”