New SARS-CoV-2 lineage has spread across many Brazilian states

By Sally Robertson, B.Sc.Mar 15 2021

Researchers in Brazil have identified the emergence of a new lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Brazil that has spread across multiple states in the country.

The SARS-CoV-2 virus is the agent responsible for the coronavirus disease 2019 (COVID-19) that continues to pose a threat to global public health and the worldwide economy.

Marilda Siqueira from the Oswaldo Cruz Institute (Fiocruz) in Rio de Janeiro and colleagues say this new variant of interest (VOI) probably emerged in August 2020 and is already widely distributed in Brazil.

Designated as N.9, the variant emerged in the B.1.1.33 lineage and comprised 35% of all B.1.1.33 sequences detected between November 2020 and February 2021.

The VOI N.9 harbors the E484K mutation in a surface structure called the spike protein, which the virus uses to bind to and infect host cells.

The E484K mutation in spike (S: E484K) is considered one of the most critical mutations since it may contribute to immune evasion. Studies have shown that it confers resistance to some monoclonal antibodies and reduces the neutralization potency of sera from convalescent and vaccinated individuals.

The researchers predict that the COVID-19 epidemic in Brazil during 2021 will be dominated by a complex array of 484K variants that will completely replace the parental 484E lineages that drove the epidemic during 2020.

The team advises that efficient mitigation measures will be crucial to reducing community transmission across Brazil and preventing the recurrence of more transmissible variants that could further exacerbate the epidemic.

A pre-print version of the research paper is available on the bioRxiv* server while the article undergoes peer review.

Study: A potential SARS-CoV-2 variant of interest (VOI) harboring mutation E484K in the Spike protein was identified within lineage B.1.1.33 circulating in Brazil. Image Credit: Pong Ch / Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

More about the epidemic in Brazil

The SARS-CoV-2 epidemic in Brazil was mainly driven by the B.1.1.28 and B.1.1.33 lineages that likely emerged in February 2020 before becoming the dominant variants in most regions by October 2020.

Since then, genomic studies revealed the emergence of two rapidly spreading variants (P.1 and P.2) within the B.1.1.28 lineage that harbor mutations in the receptor-binding domain of the spike protein.

Lineage P.1, which was first described in January 2020, is considered a variant of concern (VOC), as it harbors an unusually high number of spike mutations (including K417T, E484K, N501Y) and was associated with a second epidemic wave in the state of Amazonas.

The P.2 lineage, which was first described in October 2020, only harbors E484K in the spike and four mutations that lie outside of the spike. This lineage, which is considered a variant of interest (VOI) was the most prevalent variant detected in several states during late 2020 and early 2021.

Several variants also emerged in the B.1.1.33 lineage, including the N.1 lineage detected in the U.S., N.2 detected in Suriname and France, N.3 circulating in Argentina, and lineages N.4 and B.1.1.314 circulating in Chile. However, none of the mutations identified in these new lineages harbored mutations of concern in the spike protein.

a) Maximum likelihood (ML) phylogenetic tree of the B.1.1.33 whole-genome sequences from Brazil. The B.1.1.33 sequences with mutation S:E484K are represented by pink (VOI N.9) and green [B.1.1.33(E484K)] circles. VOI N.9 clade is highlighted in pink. The aLRT support values are indicated in key nodes and branch lengths are drawn to scale with the left bar indicating nucleotide substitutions per site. b) Geographic distribution of the VOI N.9 identified in Brazil. Brazilian states’ names follow the ISO 3166-2 standard. c) Correlation between the sampling date of B.1.1.33 sequences and their genetic distance from the root of the ML phylogenetic tree. Colors indicate the B.1.1.33 clade as indicated in a). d) Bayesian phylogeographic analysis of N.9 lineage. Tips and branches colors indicate the sampling state and the most probable inferred location of their descendent nodes, respectively, as indicated in the legend. Branch posterior probabilities are indicated in key nodes. Boxes highlight two N.9 subclades carrying additional mutations (indicated in each box). The tree was automatically rooted under the assumption of a strict molecular clock, and all horizontal branch lengths are time-scaled.

What did the current study involve?

Siqueira and colleagues conducted a genomic survey of SARS-CoV-2-positive samples sequenced by the Fiocruz COVID-19 Genomic Surveillance Network between 12^th March 2020 and 27^th January 2021.

They identified 422 sequences within the B.1.1.33 lineage that were then combined with B.1.1.33 Brazilian genomes that were available in the GISAID database EpiCoV by 1^st March 2021.

Mutational profiling revealed that the S:E484K mutation was present in 34 of the B.1.1.33-derived sequences.

Phylogenetic analysis of the sequences identified a potential new VOI designated as lineage N.9 that contained the S:E484K mutation and was detected in different states across Brazil between November 2020 and February 2021.

The VOI N.9 was detected in ten Brazilian states, suggesting that this lineage is already widely distributed across the country.

The variant was first detected in Sao Paulo on the 11^th November, 2020, and then identified later in the South (Santa Catarina), North (Amazonas and Para) and Northeast (Bahia, Maranhao, Paraiba, Pernambuco, Piaui, and Sergipe) regions.

“A major global shift in the SARS-CoV-2 fitness landscape”

Further analysis suggested that the N.9 lineage probably emerged in Sao Paulo, Bahia or Maranhao around the 15^th of August 2020.

“The onset date of the VOI N.9 here estimated around mid-August roughly coincides with the estimated timing of emergence of the VOI P.2 in late-July and shortly precedes the detection of a major global shift in the SARS-CoV-2 fitness landscape after October 2020,” write the researchers.

The team says the VOI N.9 is already widely distributed in the country and made up 35% of the B.1.1.33 sequences detected between November 2020 and February 2021.

Siqueira and colleagues say the S:E484K mutation has emerged independently in various different VOCs and VOIs that are spreading rapidly around the world.

“It is probably an example of convergent evolution and ongoing adaptation of the virus to the human host,” they write.

Efficient mitigation measures will be “crucial”

The researchers say they expect that the epidemic in Brazil during 2021 will be dominated by a complex array of B.1.1.28(484K) and B.1.1.33(484K) variants that will completely replace the parental 484E lineages that drove the epidemic in 2020.

“Implementation of efficient mitigation measures in Brazil is crucial to reduce community transmission and prevent the recurrent emergence of more transmissible variants that could further exacerbate the epidemic in the country,” concludes the team.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources