COVID-19: Two New Delta Sublineages Threats – AY.43.1 And AY.43.2 Are Busy Gaining Ground

While the world has been over preoccupied with the Omicron variant, two new sub-lineages from a Delta Subvariant AY.43 have emerged in Brazil with worrying mutations that that indicate possible enhanced transmissibility and immune evasiveness coupled with drastic changes in viral functions.

The two new novel Brazilian sub-lineages AY.43.1 and AY.43.2 belonging to the Delta AY.43 subvariant lineage. Both the novel sublineages were defined by the following characteristic nonsynonymous mutations: ORF1ab:A4133V and ORF3a:T14I for AY.43.1 and ORF1ab:G1155C for AY.43.2.

According to local physicians and medical experts, the two new variants could be behind the new small cluster surges in Brazil originating in Sao Paulo with many who were fully vaccinated before or had previous infections getting re-infected and displaying moderate to severe symptoms.

Local health authorities are saying that it is still too early to make any inferences and more studies are needed to assess the situation.

A team of researchers from Sao Paulo University and the Butantan Institute in Brazil have already published a preprint paper on the discovery of this new Delta sub-lineages.

https://www.medrxiv.org/content/10.1101/2021.11.29.21266819v1

Currently in Brazil have been applied more than 157 million doses of anti-SARS-CoV-2 vaccine and the individuals who have been fully vaccinated are approximately 124 million, which makes Brazil one of the most vaccinated nations in the world. In Brazil, on the background of this solid process of vaccination, the first cases of Delta VOC introductions were reported (1).

Although now there is a full substitution of the dominant Brazilian gamma VOC by the Delta sublineages. Despite the full substitution of the pre-existing gamma VOC in Brazil with the delta VOC, no exponential growth of the new cases has been observed, most probably due to the ongoing vaccination.

Delta VOC is highly diversified, and more than 120 sublineages have been classified within the Pango lineages (https://cov-lineages.org/) with the frequent description of novel lineages and sublineages.

We assume that the presence of massive vaccination in Brazil may also help for the selection of novel SARS-CoV-2 lineages and sublineages due to the accumulation of viral mutations leading to viral fitness. The molecular surveillance of the SARS-CoV-2 variants is of crucial importance for tracking the genomic profile of this virus and the accumulation of mutations which on one hand can alter the viral functions in terms of infectivity and transmissibility and on the other to be important for the emergence of novel variants, lineages, and sublineages which can exert significant pressure on the healthcare system of a given country (2).

In this study, we identified two novel Brazilian sublineages belonging to the AY.43 lineage, which were named AY.43.1 and AY.43.2, suggested due to their specific clade clustering within the main AY.43 lineage.

Most of these sequences originated from the city of São Paulo and the genome monitoring was performed by the Network for Pandemic Alert of SARS-CoV-2 Variants of the São Paulo State.

Discussion

In this study, we provide a preliminary report of the characterization of two novel AY.43 sublineages with probable Brazilian origin, due to the observed specific clustering and specific mutation profile observed in the phylogenetic tree generated by Nextstrain. Additionally, depending on the type of mutation (localization in ORF1a or ORF3a) we hypothesized the subdivision of the AY.43 strain into two sublineages designated as AY.43.1 and AY.43.2.

The obtained data shows the importance of the SARS-CoV-2 genomic surveillance for the identification of emerging lineages. This is particularly important because SARS-CoV-2 emerging lineages can exert an enormous impact on the public health systems due to increased infectivity and transmission (2).

In the newly characterized sublineages, we defined the mutations A4133V and G1155C in the ORF1a and the T14I mutation in the ORF3a, which were non-synonymous. To our knowledge, the impact of these mutations is unknown, except for the T14I, which shows deleterious effects on the viral proteins (11).

A nonsynonymous mutation in ORF3a, which is a conserved protein involved in viral replication and release (12), may affect viral functions in addition to the mutational constellation defined for the Delta VOC. Based on the performed analysis the newly classified AY.43.1 and AY.43.2 sublineages probably have Brazilian origin as were composed of sequences obtained from Brazil.

Further studies are necessary to investigate the dissemination in these two sublineages in Brazil, but preliminary results show that the majority of AY.43.1 and AY.43.2 sequences originated from the city of São Paulo.

In conclusion, we show that SARS-CoV-2 genome monitoring is crucial for the prompt characterization of SARS-CoV-2 novel lineages and sublineages. By this approach, we can timely detect the presence of novel SARS-CoV-2 variants and implement strategies for preventing their dissemination which can have further implications on the ongoing SARS-CoV-2 vaccination and public health policies.