Brazil’s COVID-19 response has faced challenges due to the continuous emergence of variants of concern (VOCs), emphasizing the need for ongoing genomic surveillance and retrospective analyses of past epidemic waves. Rio Grande do Sul (RS), Brazil’s southernmost state, has crucial international borders and trades with Argentina and Uruguay, along with significant domestic connections. The source and sink of transmission with both national and international hubs raises questions about the RS role in the transmission of the virus, which has not been fully explored. Nasopharyngeal samples from various municipalities in RS were collected between June 2020 and July 2022. SARS-CoV-2 whole genome amplification and sequencing were performed using high-throughput Illumina sequencing. Bioinformatics analysis encompassed the development of scripts and tools to take into account epidemiological information to reduce sequencing disparities bias among the regions/countries, genome assembly, and large-scale phylogenetic reconstruction. Here, we sequenced 1,480 SARS-CoV-2 genomes from RS, covering all major regions. Sequences predominantly represented Gamma (April-June 2021) and Omicron (January-July 2022) variants. Phylogenetic analysis revealed a regional pattern for transmission dynamics, particularly with Southeast Brazil for Gamma, and a range of inter-regional connections for Delta and Omicron within the country. On the other hand, international and cross-border transmission with Argentina and Uruguay was rather limited. We evaluated the three VOCs circulation over two years in RS using a new subsampling strategy based on the number of cases in each state during the circulation of each VOC. In summary, the retrospective analysis of genomic surveillance data demonstrated that virus transmission was less intense between country borders than within the country. These findings suggest that while non-pharmacological interventions were effective to mitigate transmission across international land borders in RS, they were unsuficient to contain transmission at the domestic level.

The authors have declared no competing interest.

Yes

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical clearance for this study was granted by CEP UFSM under the authorization number 52939821.5.0000.5346 and 47588621.7.1001.5346 and by CEP from Escola de Saúde Pública/SES-RS under the authorization number CAAE: 67181123.1.0000.5312.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes