ABSTRACT
Uruguay was able to control the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein we analyzed the country-wide genetic diversity of SARS-CoV-2 between November, 2020 and April, 2021. Our findings identified that the most prevalent viral variant during late 2020 was a B.1.1.28 sublineage carrying mutations Q675H+Q677H in the viral Spike, now designated as lineage P.6. This new lineage P.6 probably arose around November 2020, in Montevideo, Uruguays capital department and rapidly spread to other Uruguayan departments, with evidence of further local transmission clusters, also spread sporadically to the USA and Spain. The Q675H and Q677H mutations are in the proximity of the polybasic cleavage site at the S1/S2 boundary and also arose independently in many SARS-CoV-2 lineages circulating worldwide. Although the lineage P.6 was replaced by the Variant of Concern (VOC) P.1 as the predominant viral strain in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H+Q677H in VOCs should be of worldwide interest.
ABSTRACT
BackgroundUruguay is one of the few countries in the Americas that successfully contained the COVID-19 epidemic during the first half of 2020. Nevertheless, the intensive human mobility across the dry border with Brazil is a major challenge for public health authorities. We aimed to investigate the origin of SARS-CoV-2 strains detected in Uruguayan localities bordering Brazil as well as to measure the viral flux across this [~]1,100 km uninterrupted dry frontier. MethodsUsing complete SARS-CoV-2 genomes from the Uruguayan-Brazilian bordering region and phylogeographic analyses, we inferred the virus dissemination frequency between Brazil and Uruguay and characterized local outbreak dynamics during the first months (May-July) of the pandemic. FindingsPhylogenetic analyses revealed multiple introductions of SARS-CoV-2 Brazilian lineages B.1.1.28 and B.1.1.33 into Uruguayan localities at the bordering region. The most probable sources of viral strains introduced to Uruguay were the Southeast Brazilian region and the state of Rio Grande do Sul. Some of the viral strains introduced in Uruguayan border localities between early May and mid-July were able to locally spread and originated the first outbreaks detected outside the metropolitan region. The viral lineages responsible for Uruguayan suburban outbreaks were defined by a set of between four and 11 mutations (synonymous and non-synonymous) respect to the ancestral B.1.1.28 and B.1.1.33 viruses that arose in Brazil, supporting the notion of a rapid genetic differentiation between SARS-CoV-2 subpopulations spreading in South America. InterpretationAlthough Uruguayan borders have remained essentially closed to non-Uruguayan citizens, the inevitable flow of people across the dry border with Brazil allowed the repeated entry of the virus into Uruguay and the subsequent emergence of local outbreaks in Uruguayan border localities. Implementation of coordinated bi-national surveillance systems are crucial to achieve an efficient control of the SARS-CoV-2 spread across this kind of highly permeable borderland regions around the world. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSince the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent of coronavirus disease 19 (COVID-19), was first detected in South America on February 26, 2020, it has rapidly spread through the region, causing nearly 350,000 deaths by December, 2020. In contrast to most American countries, Uruguay avoided an early exponential growth of SARS-CoV-2 cases and during the first six months of the pandemic it registered the lowest incidence of SARS-CoV-2 cases and deaths among South American countries. The intensive cross-border human mobility through the [~]1,100 km uninterrupted dry frontier between Uruguay and Brazil, might poses a major challenge for long-term control of the epidemic in Uruguay. Previous genomic studies conducted in Uruguay have analyzed sequences mostly sampled at the capital city, Montevideo, and detected prevalent SARS-CoV-2 lineages different from those described in Brazil, thus finding no evidence of frequent viral exchanges between these countries. Added value of this studyHere we present the first genomic study of SARS-CoV-2 strains detected in different Uruguayan and Brazilian localities along the bordering region. The samples analyzed include 30% (n = 59) of all laboratory confirmed SARS-CoV-2 cases from Uruguayan departments at the Brazilian border between March and July, 2020, as well as 68 SARS-CoV-2 sequences from individuals diagnosed in the southernmost Brazilian state of Rio Grande do Sul between March and August, 2020. We demonstrate that SARS-CoV-2 viral lineages that widely spread in the Southeastern Brazilian region (B.1.1.28 and B.1.1.33) were also responsible for most viral infections in Rio Grande do Sul and neighboring Uruguayan localities. We further uncover that major outbreaks detected in Uruguayan localities bordering Brazil in May and June, 2020, were originated from two independent introduction events of the Brazilian SARS-CoV-2 lineage B.1.1.33, unlike previous outbreaks in the Uruguayan metropolitan region that were seeded by European SARS-CoV-2 lineages. Implications of all the available evidenceOur findings confirm that although Uruguayan borders have remained essentially closed to non-Uruguayan citizens, dissemination of SARS-CoV-2 across the Uruguayan-Brazilian frontier was not fully suppressed and had the potential to ignite local transmission chains in Uruguay. These findings also highlight the relevance of implementing bi-national public health cooperation workforces combining epidemiologic and genomic data to monitor the viral spread throughout this kind of highly permeable dry frontiers around the world.