What is the new omicron COVID-19 Sub-Variants BA.4 and BA.5?
The World Health Organization (WHO) has recently identified two novel variants within the Omicron lineage designated as BA.4 and BA.5. Both the BA.4 and the BA.5 variants have been added to the monitoring list of the World Health Organization (WHO) and are currently under investigation regarding mutations that could potentially alter their viral characteristics such as transmissibility, symptom severity, and immune escape. Here’s what we know so far about these new variants.
What is a virus mutation?
Mutation is considered a normal and common behavior for viruses. Mutations are essentially random changes in the genetic code of the virus. These changes occur due to errors that happen during the replication process. Mutations are particularly common for viruses carrying RNA as their genetic material, such as coronaviruses and influenza viruses because they lack a strong error correction mechanism that locates, excises, and repairs the errors while they replicate.
As these mutations are random, their impact for the resulting virus is highly variable. Many times, mutations do not have significant impact on viral behavior, and they can even impair the virus. However, some mutations may occasionally help a virus to escape immunity, invade our cells, and replicate more easily. Due to selection, advantageous genetic errors persist over generations and become part of normal viral genome in time. As these mutations accumulate, novel variants of a virus strain emerge.
Apart from the type of viral genome a virus is containing, the severity of its spread, and its interactions with other viruses or variants can also affect the rate of mutation. In general, in the cases that the rate of transmission is high, and many variants are simultaneously in circulation, mutations are more likely to happen, and variants are more likely to emerge. Experts also point out that new variants are frequently identified because with the advancement of diagnostic and medical technology, it has become easier than ever to track and identify variants.
How do we identify the new variants?
New variants are identified, tracked, and characterized through the analysis of specimen by a process called genome sequencing. In essence, genome sequencing enables the extraction of the genetic material of a pathogen, decoding of the genes, and the comparison of the new sequence data with a reference sequence. Genome sequencing helps scientists to identify a certain variant, understand its characteristics, infer its lineage, estimate its prevalence, and assess the impact of vaccines or treatment against it. Genomic surveillance, referring to the accumulation of genetic sequencing data, also help accelerate and simplify screening for new variants and emerging trends.
Which countries have confirmed BA.4 and BA.5 cases?
According to the report by the UK Health Security Agency dated 8 April 2022, 48 BA.4 samples in total have been reported via GISAID. The majority of these genomes were reported from South Africa (41), while the rest was from Denmark (3), Botswana (2), England (1), and Scotland (1). For the BA.5 variant, all the 27 samples have been reported from South Africa.
What do we know about the BA.4 and BA.5 variants?
The BA.4 and BA.5 variants have been discovered as part of horizon scanning on 4 April 2022. Although studies investigating the exact phylogeny and characteristics of the BA.4 and BA.5 variants are in-progress, here is what the data has demonstrated so far.
The data shows that the BA.4 variant shares all but 8 mutations/ deletions with the BA.2 variant. Significant exceptions include a spike 69/70 deletion that will lead to an S-gene target failure which can be used as a marker to identify the variant and the L452R mutation which is associated with high infectivity and pathogenicity. With sample dates between 25 February and 25 March 2022, the BA.5 variant shares all but 4 of the same mutations/deletions with the BA.4 variant including the spike 69/70 deletion and the L452R mutation.
How concerned should we be about Omicron BA.4 and BA.5 variants?
Many experts agree that there is no need to be alarmed just yet. As of now, there is no evidence to suggest that the BA.4 and BA.5 variants are more infectious or clinically dangerous than the original Omicron mutation. Still, it is noted that this could change as the data grows and more cases are detected.
However, several scientists call attention to the L452R mutation shared both by variants and state that it may give the BA.4 and BA.5 variants a significant advantage in transmission, pathogenicity, and immune escape. Indeed, as the L452 is located very close to the angiotensin converting enzyme 2 (ACE 2) interaction interface, the L452R mutation is closely associated with improved cell attachment and evasion of immunity, which together are much likely to increase transmissibility, infectivity, pathogenicity. In fact, a recent study on mice has shown that the L452R mutation has significantly improved the ability of Omicron to infect lung tissues of humanized ACE2 mice. Moreover, the results of a genome-wide phylogenetic analysis demonstrate that the emergence of both the BA.4 and the BA.5 variants may be specifically triggered by the L452R mutation. Considering how the L452R mutation is present in many variants such as delta, epsilon, lambda, kappa, and iota with separate origins, it may also be suggested that there is a strong positive selection for this mutation.
Do vaccines work against Omicron BA.4 and BA.5 subvariants?
As very few cases of the BA.4 and BA.5 have been reported, there is currently no data available demonstrating the ability of these variants to escape vaccine-elicited immunity. Our current vaccines have so far proven effective against the variants within the Omicron lineage such as the BA.1 and BA.2. Still, as mentioned above, several scientists argue that some of the mutations undergone by the BA.4 and BA.5 variants might have made these variants more immune-evasive than their siblings.
However, experts agree that vaccination remains our most effective protection against death and severe disease regardless of the variant and advise every eligible person to get fully vaccinated, and if possible, receive their booster shots to get the best protection.
What are the precautions against the BA.4 and BA.5 variants?
The World Health Organization (WHO) has added the BA.4 and BA.5 variants to its monitoring list. As such, the precautions against the BA.4 and BA.5 variants remain essentially the same as they are for other variants. However, additional measures may be implemented in the future in accordance with the upcoming data.
Will the COVID-19 Rapid Antigen Test Kits work against the BA.4 and BA.5 variants?
Antigens are proteins or parts of proteins that serve as a target for a specific antibody in a reactive test strip. Spike proteins and nucleocapsid proteins are examples of antigen we use. Most of the mutations in the Omicron BA.4 and BA.5 variants are carried on the spike protein region. This can reduce sensitivity or result in non-functional tests for rapid antigen tests using SARS-CoV-2 spike protein as a target. Those using nucleocapsid protein as a target such as our RapidFor™ SARS-CoV-2 Rapid Antigen Test Kit, on the other hand, are less likely to be influenced by mutations in terms of sensitivity and functionality.