Comparative Genomics and Characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern From Amazonas, Brazil

Abstract

BackgroundP.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality, and immune evasion, leading to reinfections and potentially reduced efficacy of vaccines and neutralizing antibodies.MethodsThe samples of 276 patients from the State of Amazonas were sent to a central referral laboratory for sequencing by gold standard techniques, through Illumina MiSeq platform. Both global and regional phylogenetic analyses of the successfully sequenced genomes were conducted through maximum likelihood method. Multiple alignments were obtained including previously obtained unique human SARS-CoV-2 sequences. The evolutionary histories of spike and non-structural proteins from ORF1a of northern genomes were described and their molecular evolution was analyzed for detection of positive (FUBAR, FEL, and MEME) and negative (FEL and SLAC) selective pressures. To further evaluate the possible pathways of evolution leading to the emergence of P.1, we performed specific analysis for copy-choice recombination events. A global phylogenomic analysis with subsampled P.1 and B.1.1.28 genomes was applied to evaluate the relationship among samples.ResultsForty-four samples from the State of Amazonas were successfully sequenced and confirmed as P.1 (Gamma) lineage. In addition to previously described P.1 characteristic mutations, we find evidence of continuous diversification of SARS-CoV-2, as rare and previously unseen P.1 mutations were detected in spike and non-structural protein from ORF1a. No evidence of recombination was found. Several sites were demonstrated to be under positive and negative selection, with various mutations identified mostly in P.1 lineage. According to the Pango assignment, phylogenomic analyses indicate all samples as belonging to the P.1 lineage.ConclusionP.1 has shown continuous evolution after its emergence. The lack of clear evidence for recombination and the positive selection demonstrated for several sites suggest that this lineage emergence resulted mainly from strong evolutionary forces and progressive accumulation of a favorable signature set of mutations.

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

“… 42 , 43 One month later, the Gamma variant (P.1) was reported in Brazil, and the travelers arriving in Japan from Brazil. 44 , 45 Delta variant (B.1.617.2) was first detected in India in May 2021 and rapidly became the dominant variant worldwide by late 2021, while some sub-clade of Delta variant displayed a unique penchant in epidemic areas, such as Clade 20I (Delta) in some parts of Asia. 41 , 46 , 47 Delta-dominant epidemic lasted quite long in the world until Omicron (B.1.1.529) in November 2021, which was first reported in South Africa, 48 , 49 and soon in Chinese Hong Kong.…”

“…Such as mutation P314L at Nsp12 was reported to decrease the protein stability. 27 , 45 , 61 , 134 , 158 – 163

Fig. 4 Heatmap of the mutation site and the mutational impact of SARS-CoV-2 variants on the non-structural proteins.

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Impact of COVID-19 vaccination: a global perspective

“…Subsequently, several variants of concerns (VOC) were identified such as B.1.1.7 (Alpha) in the UK (September 2020) ( 3 ), B.1.351 (Beta) in South Africa (December 2020) ( 4 ), P.1 (Gamma) in Brazil (January 2021) ( 5 ), and the B.1.617 (Delta) variant in India (January 2021) ( 6 ). It is notably evident that the mortality rate due to the COVID-19 disease surged in the countries where the newer variants were discovered ( 7–10 ). The B.1.1.7 (Alpha) variant has been linked with an increased risk of transmissibility, hospitalization, and death ( 8 , 11–14 ).…”

COVID-19 mortality in Brazil, 2020-21: consequences of the pandemic inadequate management

“…Lineage B.1.1.7 was associated with a higher lethality rate in the United Kingdom. The Manaus variant (P.1) was 1.7 to 2.4 times more transmissible than the other lineages of the virus [4][5][6]. The "Omicron" lineage became the predominant SARS-CoV-2 VOC in several countries from November 2021 and on, becoming the dominant variant circulating globally in 2022 [7].…”