Mutation hotspots, geographical and temporal distribution of SARS-CoV-2 lineages in Brazil, February 2020-2021: insights and limitations from uneven sequencing efforts

Abstract

The COVID-19 pandemic has already reached approximately 110 million people and it is associated with 2.5 million deaths worldwide. Brazil is the third worst-hit country, with approximately 10.2 million cases and 250 thousand deaths. Unprecedented international efforts have been established in order to share information about epidemiology, viral evolution and transmission dynamics. However, sequencing facilities and research investments are very heterogeneous across different regions and countries across the globe. The understanding of the SARS-CoV-2 biology is a vital part for the development of effective strategies for public health care and disease management. This work aims to analyze the available genomes sequenced in Brazil between February 2020 and February 2021, in order to identify mutation hotspots, geographical and temporal distribution of SARS-CoV-2 lineages in the Brazilian territory by using phylogenetics and phylodynamics analyses from high-quality genomes. We describe heterogeneous and episodic sequencing efforts, the progression of the different lineages along time, evaluating mutational spectra and frequency oscillations derived from the prevalence of novel and specific lineages across different Brazilian regions. We found at least seven major (1-7) and two minor clades (4.2 and 5.3) related to the six most prevalent Brazilian lineages and described its distribution across the Brazilian territory. The emergence and recent frequency shift of lineages (P.1 and P.2) containing mutations of concern in the spike protein (e. g., E484K, N501Y) draws attention due to their association with immune evasion and enhanced receptor binding affinity. Improvements in genomic surveillance are of paramount importance and should be extended in Brazil to better inform policy makers and enable precise evidence-based decisions to fight the COVID-19 pandemic.

Emergence of the novel SARS-CoV-2 lineage VUI-NP13L and massive spread of P.2 in South Brazil

“…Of the five main circulating lineages, B.1.1.33 and B.1.1.28 were the most predominant, mainly in the initial period of the study. Our findings are supported by other Brazilian sequencing studies, which showed that B.1.1.33 and B.1.1.28 are the most prevalent lineages of the country, including South Brazil [ 16 ].…”

“…The geographic distribution of lineages was evaluated in four RS-sampled regions since the first detection of VUI-NP13L in our sampling (Fig. 4 Southeast Brazil, on 9 March 2020 and then disseminated across the country 16,24,37,38 . This lineage was also associated with outbreaks in Argentina and Uruguay, countries bordering RS 38,39 .…”

“…Regardless of the volume of COVID-19 cases in Brazil, a task force created by the scientific community was able to sequence only approximately 0.03% of all positive SARS-CoV-2 cases through the pandemic’s first year [ 16 , 17 ]. Most of the Brazilian sequences from March and April 2020 belonged to two major clades of the B lineage (B.1.1), which were later named B.1.1.28 and B.1.1.33, and phylodynamic analysis indicated that they might have been seeded in the country by multiple events [ 18 ].…”

Emergence of the novel SARS-CoV-2 lineage P.4.1 and massive spread of P.2 in South Brazil

“…Sequences evaluated in our study are restricted to 2020; therefore, we cannot rule out if the lineages are still active across southern Brazil. 16,18,20,23 . This lineage was also associated with secondary outbreaks in Argentina and Uruguay, countries bordering RS 18,24 .…”

“…According to an independent phylodynamic reconstruction, P.4.1 rapidly arrived in the southeastern and northeastern regions of Brazil and seems to have been exported to Japan, the Netherlands and England 23 . The success of the spread of P.4.1, beyond having important mutations in the spike protein (V1176F, D614G), also shared by P.2 and P.1 lineages, could be justified by the unique amino acid changes in ORF1a 16,26,27 . This gene is known to encode a polyprotein involved in the replication complex 28 .…”