As the world continues to struggle from the onslaught of COVID-19, the SARS-CoV-2 virus appears to give mankind no quarter. Now, the novel coronavirus has added another weapon to its arsenal: a new variant. On Wednesday, South African authorities announced that a variant, B.1.1.529, carrying "an unusual constellation of mutations" has been detected in the country.
According to South Africa's National Institute for Communicable Diseases (NICD), the B.1.1.529 lineage was detected in the Gauteng province of South Africa at a relatively high frequency. Along with sharing "a high number of mutations" with variants of concern (VOC) and variants of interest (VOI), the B.1.1.529 lineage also possesses mutations that are novel. However, there is uncertainty surrounding the site of its initial emergence.
"It is not surprising that a new variant has been detected in South Africa. Although the data are limited, our experts are working overtime with all the established surveillance systems to understand the new variant and what the potential implications could be. Developments are occurring at a rapid pace and the public has our assurance that we will keep them up to date," said, Dr. Adrian Puren, Acting Executive Director of NICD, in a statement.
Finding a New Variant
Viruses such as the SARS-CoV-2 often evolve as they make their way into different populations. Most of the mutations in the newer variants such as VOCs are located on the 'S- protein' or 'spike' of the SARS-CoV-2 virus. The spike is a hook-like structure present on the surface of the pathogen that it uses to invade cells.
While South Africa announced the identification of B.1.1.529, the mutant was spotted by scientists in the genome-sequencing data from the neighboring nation of Botswana. However, a sharp spike in the number of cases in the Gauteng province in November prompted researchers to collect samples from the region (between 14-23 November 2021). Alarmingly, all the analyzed specimens from the area—77–were infected with B.1.1.529.
Sharing Mutation With VOCs, VOIs
The B.1.1.529 lineage contains around 50 mutations. 30 of these variations are found on its spike protein; many of which it shares with VOCs such as Beta (B.1.351- South Africa), Delta (B.1.617.2- India), and also C.1.2 (a variant detected in South Africa on 1 September 2021). These alterations are associated with increased infectivity and immuno-evasion.
For example, the mutation P681H in B.1.1.529 has also been found in VOCs such as Alpha (B.1.1.7- UK) and Gamma, and variants of interest (VOIs) such as Mu. It enhances transmissibility. B.1.1.529 also carries a transmissibility-affecting mutation, N679K. Another mutation known as N501Y, which has been seen in other VOCs, is also present in the variant and is associated with increased viral transmission.
"It is a combination we see only exceptionally rarely. I suspect it is generally not 'stable', but it might be so, in combination with other mutations/deletions. I would definitely expect it to be poorly recognized by neutralizing antibodies relative to Alpha or Delta," explained Dr. Francois Balloux, from UCL Genetics Institute, in a comment shared by UK's Science Media Centre.
Dr. Penny Moore, from the University of Witwatersrand (WITS), told Nature. "Many mutations we know are problematic, but many more look like they are likely contributing to further evasion." Scientists from WITS were part of the large collaborative team that examined the samples Gauteng and are currently investigating the ability of the B.1.1.529 variant to potentially evade immunity acquired through prior infection, vaccination, or both.
Novel Mutations of Its Own
Despite sharing mutations with the Alpha and Beta variants, the B.1.1.529 contains variations that are novel. The NICD stated that the variant is "relatively distinct" from its fellow mutants and has a "different evolutionary pathway". For example, the B.1.1.529 lineage contains a deletion (△69-70) within the S gene. This is said to have enabled the quick identification of the new variant.
According to Dr. Tulio de Oliveira, director of the KwaZulu-Natal Research and Innovation Sequencing Platform, this very alteration can enable the quick detection and monitoring of the variant. "Because this variant (B.1.1.529) can be detected by a normal qPCR due to deletion at Spike position 69-70 (like Alpha), it will make it easy for the world to track it," he highlighted in a tweet.
Additionally, there are also ten mutations on the receptor-binding domain (RBD) of B.1.1.529's spike—the area where binding between the virus and the cell takes place—unlike only two found in the RBD of the globally dominant VOC, Delta. Another speculation surrounding the emergence of the B.1.1.529 variant is that it may have risen in immuno-compromised individuals with HIV/AIDS.
"Given the large number of mutations it has accumulated apparently in a single burst, it likely evolved during a chronic infection of an immunocompromised person, possibly in an untreated HIV/AIDS patient," suggested Dr. Balloux.
Giving Rise to Global Concern
In a press briefing organized by South Africa's health department on 25 November, Dr. Richard Lessells, from the University of KwaZulu-Natal (one of the collaborating institutions) averred, "The mutation profile gives us concern, but now we need to do the work to understand the significance of this variant and what it means for the response to the pandemic."
Dr. Sharon Peacock, from the University of Cambridge, pointed out that there had been a sudden increase in the number of COVID-19 cases in South Africa over the past ten days. While only 273 cases were recorded on 16 November, over 1,200 cases were logged on 25 November. Over 80 percent of these cases came from the Gauteng province.
In a remark shared by Science Media Centre, Dr. Peacock noted, "The epidemiological picture suggests that this variant may be more transmissible, and several mutations are consistent with enhanced transmissibility." The WHO is set to meet on Friday to assess the situation and decide on the designation of the B.1.1.529 variant. It is likely to be named 'Nu'.
The new variant has raised alarm across the world with several countries such as the UK which has imposed travel restrictions on six African nations (including South Africa) and added them to its 'red list'. Unfortunately, infections caused by the B.1.1.529 lineage have already been reported in other parts of the world such as Hong Kong and Israel.
