In the early days of the pandemic and this ‘novel’ coronavirus there were plenty of questions being asked about the threat of mutations. It is generally accepted that coronaviruses are more stable than HIV or influenza viruses. SARS-CoV-2, the virus that causes COVID-19, is a much larger virus and has a molecular ‘proofreading’ system that prevents damaging genetic errors during replication.
However, this turned out to be one of the many misconceptions of the pandemic. The coronavirus has been acquiring minor random mutations ever since it made the significant jump from animals to humans, the ‘spillover’ event that changed the world. These mutations can take the form of single-letter ‘typos’ in the viral genetic code which usually either inactivate the virus or have no effect on its behaviour.
We now know that as soon as the virus came under the transmission restraints of natural immunity in previously infected people, or reduced spread through non-pharmaceutical interventions such as distancing and masking, there was more pressure on the virus to mutate. We started to notice a change in the behaviour of these ‘escape mutants’, with increased transmissibility or increased virulence or decreased susceptibility to antibodies. The last few months have seen a number of worrying ‘variants’ that have alerted the landscape in terms of the way out of this pandemic.
What is a variant?
When a virus is widely circulating in a population and causing many infections, the likelihood of the virus mutating increases and that can cause a new variant or strain. The more opportunities a virus has to spread, the more it replicates – and the more opportunities it has to undergo changes or ‘mutations’.
A ‘mutation’ is an error in the basic replication of a virus affecting one of the genes that instructs the protein building blocks that make up the virus. Viruses mutate all the time but most mutations are irrelevant and disappear.
A ‘variant’ emerges when a combination of mutations are selected through repeated replications.
A ‘strain’ describes a variant that produces a virus that has mutated in such a way as to produce distinctly different characteristics, such as in transmissibility or virulence.
Around the world, scientists are closely observing mutations identified in the virus that causes COVID-19 and variants and strains that result.
Do new variants of COVID cause more serious illness?
Most viral mutations have little to no impact on the virus’s ability to cause infections and disease. But depending on where the changes are located in the virus’s genetic material, they may affect a virus’s properties, such as increased transmission or severity of disease. Infections with the new variant B.1.1.7, first discovered in the UK, were associated with an estimated increased risk of death of around 64%.
Several new variants of the novel coronavirus are causing concern
Several new variants of the novel coronavirus are causing concern, partly due to mutations in part of the virus known as the spike protein. Mutations to the spike protein may affect how easily spread the virus is. The spike protein is also the basis of current COVID-19 vaccines, which seek to generate an immune response against it. Even more worryingly, as we plot a path out of this pandemic, is the ability of certain variants to partially evade neutralising antibodies, thus making vaccines less effective in suppressing the disease.
How many COVID variants are there?
New variants are detected every week but there are currently five prominent variants of the SARS-CoV-2 creating concern. These new variants seem to be highly transmissible and are causing more infections with the COVID-19 virus. B.1.1.7 strain first detected in the UK, B.1.351 strain first detected in South Africa and P.1 strain first detected in Brazil.
B.1.1.7 / Alpha variant
First identified in October 2020
Genomic sequencing analysis in the UK detected an emerging variant, later termed B.1.1.7. It contains 17 mutations, including several in the spike protein. Epidemiological studies indicate that the B.1.1.7 strain is 30% to 80% more transmissible than the original virus, meaning it appears to spread more easily. However, it does not increase disease severity or risk of death, according to an observational study of patients in London hospitals published in The Lancet Infectious Diseases.
B.1.351 / Beta variant
First identified in October 2020
B.1.351 shares some mutations with B.1.1.7 but has 9 other mutations on the spike protein. Scientists are concerned about a specific mutation called E484K that appears in the South African variant that may help the virus evade the immune system and vaccines. It is also thought to have a high potential for transmission. There are no data yet to suggest an increased risk of death due to this variant. Importantly, B.1.351 strains are less effectively neutralised by convalescent plasma from patients with COVID-19 and by sera from those vaccinated with several vaccines in development. The worry remains that current vaccines are less effective against this strain.
P.1 / Gamma variant
First identified in January 2021
The P.1 variant was discovered at the same time as the similar P.2 variant. The P.1 variant has more mutations and has attracted more interest, though both variants have the E484K mutation. This variant has been implicated in the surge of infections that struck Manaus, in the Brazilian Amazon, leaving the health-care system on the brink of collapse in early 2021. The level of genomic sequencing and epidemiological surveys are not as strong in Brazil, where the health authorities continue to battle a sustained and deadly surge in COVID-19, but studies have shown the P1 variant to be as much as 2.5x more contagious than the original coronavirus and more resistant to antibodies.
B.1.617 / Delta variant
First identified in October 2020
The WHO has designated the B.1.617 variant, first detected in India, a variant of global concern. The variant has three lineages, of which B.1.617.2 is the fastest growing. While B.1.617.2 does not have the E484Q mutation seen in the other two Indian variants that might help it to escape the body’s immune response, it has other mutations, including a novel one called T478K. Data from PHE showed evidence of higher transmissibility than the B.1.1.7 variant and reduced neutralisation. However, vaccine effectiveness against symptomatic disease from the B.1.617.2 variant was found to be only slightly lower after 2 doses compared to the B.1.1.7 variant – Pfizer reduced the risk of serious disease and hospitalisation by 94%, while AstraZeneca reduced this by 92%. It should be noted that vaccines were only 33% effective against symptomatic disease from B.1.617.2, 3 weeks after the first dose, compared to around 50% effectiveness against the B.1.1.7 variant.
B.1.1.529 / Omicron variant
First identified in November 2021
This newly discovered variant was recently found in samples from early November 2021 in Southern Africa. This is a highly divergent variant compared to the initial SARS-CoV-2 variant from Wuhan, China, with over 30 separate mutations in the spike protein. This is the highest number of mutations seen yet in a variant. There are concerns that the mutations present may confer ability to transmit more easily than the current dominant Delta variant and worries that it may be able to evade efficient detection from the immune system. At present, we are awaiting further data to confirm this variant’s transmissibility and immune response.
COVID variants and vaccines
The COVID-19 vaccines that are currently in development or have been approved are expected to provide at least some protection against new virus variants because these vaccines elicit a broad immune response including antibodies and a T-cell response. Therefore, changes or mutations in the virus should not make vaccines completely ineffective. In the event that any of these vaccines prove to be less effective against one or more variants, scientists are already developing vaccine ‘boosters’ to enhance the protection against these variants.
Stopping the spread at the source remains crucial to prevent future new variants
Stopping the spread at the source remains crucial to prevent future new variants emerging and becoming established. Current measures to reduce transmission – including frequent hand washing, wearing a mask, physical distancing, good ventilation and avoiding crowded places or closed settings – continue to work against new variants by reducing the amount of viral transmission and therefore also reducing opportunities for the virus to replicate and mutate.
Scaling up vaccine manufacturing and rolling out vaccines as quickly and widely as possible will also be critical ways of protecting people before they are exposed to the virus and the risk of new variants. Priority should be given to vaccinating high-risk groups everywhere to maximise global protection against new variants and minimise the risk of transmission. As Dr Tedros Adhanom Ghebreyesus continues to stress to the world, “no-one is safe until everyone is safe” and as long as transmission continues there is the potential for variants to arise that are more transmissible, more deadly or less susceptible to natural immunity or vaccine-induced immunity.