THE key point which is the most important factor determining whether COVID-19 is here to stay or whether we can eradicate this “virus”, is a mutation, says Dr Vinod Balasubramaniam from Jeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia.
“The virus continues to evolve through mutation, evading the immunity built by existing vaccines,” says Vinod.
Mutation: The gameplay
Viruses mutate because they’re constantly making copies of themselves in enormous numbers and each time it is transmitted from one person to another, the chances of making errors (mutation) are high, especially in RNA viruses like SARS-CoV-2.
Vinod says that mutations are an essential evolutionary process particularly pertinent in the ever-changing nature of RNA viruses in adapting to their host. The mutation increases the genetic diversity of the virus, creating the different variants and subvariants over time.
Vinod explains mutation using this analogy. “Think of it this way. If you were writing a draft of something millions of times on a computer, extremely quickly, you would probably make some typos. This is what is happening across the globe where a large population is involved. The longer the pandemic rages on, the more chances the virus has to evolve, especially in unvaccinated individuals.”
This was the case for the current rapidly spreading BA lineage (sometimes known as B.1.1.529) which the World Health Organization labelled Omicron. Omicron has spread rapidly, representing almost all current cases with genomes sequenced globally.
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Because Omicron has spread swiftly and has had many opportunities to mutate, it has also acquired specific mutations of its own. These have given rise to several sub-lineages, or sub-variants or what I call a variant’s variant.
The first two were labelled BA.1 and BA.2. The current list now also includes BA.1.1, BA.3, BA.4 and BA.5. and the recent BA.2.75.
How are these sub-variants different?
“Currently, the BA.4 and BA.5 seem to dominate all the other subvariants worldwide. The two subvariants are more similar to BA.2 than to the BA.1 strain that kicked off Omicron waves late last year. But BA.4 and BA.5 carry their own unique mutations, including changes called L452R and F486V in the viral spike protein that might tweak its ability to latch onto host cells and evade immune responses,” Vinod explains.
This explains why people who had previous COVID-19 infection and those who have been fully vaccinated and boosted are still contracting Covid-19 caused by these subvariants.
Here is more science given by the microbiologist. He says recent data shows three-fold reductions of neutralising antibody titres induced by vaccination and infection against BA.4 and BA.5 compared with BA.1 and BA.2, which are already substantially lower than the original COVID-19 variants. This antigenic distance is similar to that between the Delta variant and the ancestral virus (Wuhan strain) and thus is likely to lead to more breakthrough infections in the coming months. A key question now is whether BA.4 and BA.5 would out-compete BA.1 and BA.2, which poses less of an antigenic threat.
How transmissible are the new variants?
We measure how contagious a disease is by the basic reproduction number (R0). This is the average number of people an initial case infects in a population with no immunity (from vaccines or previous infection).
New mutations give the virus an advantage if they can increase transmissibility:
- The original Wuhan strain has an R0 of 3.3
- Delta has an R0 of 5.1
- Omicron BA.1 has an R0 of 9.5
- BA.2, which is 1.4 times more transmissible than BA.1, and so has an R0 of about 13.3
- BA.4 and BA.5 has an R0 of 18.6 (similar to measles, the most infectious viral disease)
Severity of the current BA.4. and BA.5.
Vinod cites recent studies to explain the severity.
A recent pre-print publication from a Japanese research group found that in lab-based, cell-culture experiments, BA.4/5 was able to replicate more efficiently in the lungs than BA.2. In hamster experiments, it developed into a more serious illness.
However, data from South Africa and the United Kingdom found that their BA.4/5 wave didn’t see a major increase in severe disease and death.
“This is possible because of the high rates of immunity due to previous infections. Our high rates of vaccine-induced immunity might have a similar protective effect in Malaysia,” says Vinod.
Can the existing vaccines protect us?
To this question, here is what Vinod says.
“We know from the beginning vaccines alone will not end this pandemic, in part because of more transmissible new variants and also because vaccines are primarily designed to protect against severe disease and death. Recent data show that each new subvariant of Omicron has been better able to evade immunity from vaccination than its predecessor.”
Although current vaccines based on the Wuhan strain will still provide some protection against serious illness and death, chances of reinfection are high with the current BA.4. and BA.5. variants and we might experience mild to moderate symptoms, especially for those who are in the vulnerable group (elderly above 60, individuals with comorbidities, children, immunocompromised individuals). It is absolutely pertinent, and this group gets their second booster shot.
While infections are increasing steadily in Malaysia and other parts of the world, the mortality rate is not as high as the time when the Delta variant was at its peak comparatively. While our previous vaccinations still provide us with some form of immunity, if BA.4. and BA.5 continue to surge; the second booster doses are absolutely pertinent to reduce the burden in hospitals (especially with waning immunity for individuals who received their booster doses past 6 months). As of now, the hospitals are still coping and there is no urgent need to there is no need to re-introduce lockdown similar to previous years.
In the pipeline
Announcements from Pfizer and Moderna on their upcoming COVID19 bivalent vaccines represent hope in controlling the current surge of infections and disease by the sub-variants BA.4 and BA.5.
“Current vaccines by themselves are insufficient to stem transmission, and so increases in cases should be expected whenever public health and social measures are lifted, irrespective of vaccination coverage. I believe we should not let our guards down to continue with effective measures as we bring transmission under control. This includes, for example, wearing well-fitting masks in crowded areas, hand hygiene, proper cough etiquette, improving the ventilation of indoor spaces, avoiding crowded spaces and being supported to stay home if unwell. Self-testing also plays an extremely important role in reducing community-driven transmission. This actually has a direct impact on a number of cases and therefore mortality rates, especially in vulnerable groups,” Vinod concludes.
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