Can new Omicron subvariants evade vaccine immunity?

Many parts of Western Europe and the United States are seeing a rise in COVID-19 cases thought to be driven by new subvariants of Omicron. These rises come alongside the easing of safety measures that were previously put in place to curb the spread of the SARS-CoV-2 virus, testing being scaled back, and COVID booster vaccine take-up at lower-than-expected levels.

The latest data shows cases are on the rise in Germany, France, the United Kingdom, Italy, Spain, Greece and Denmark. Portugal, a popular holiday destination for many people each summer, is experiencing the biggest surge. Hospital admissions have risen in several countries including France and England, according to data analysed by the Financial Times.

In the UK, data from the Office for National Statistics (ONS), released on June 17, shows that COVID infections are up 43 percent week on week.

Remarking on the ONS data while speaking at an Independent SAGE (a group of scientists who advise the UK government) meeting on June 17, Kit Yates, a senior lecturer in the department of mathematics at the University of Bath, said, “It is pretty much official from the latest ONS data that the UK has entered the next wave of COVID. It is most concerning to see that there has been an increase in COVID infections in older age groups and in the 50-59 age group who have not been offered another booster yet.”

What is driving the new COVID-19 waves?

The uptick in new COVID cases and hospital admissions is thought to be driven largely by new subvariants of the Omicron variant of SARS-CoV-2, known as BA.4 and BA.5. The BA.5 subvariant of Omicron is now the dominant variant in Portugal. In Germany, where admissions have been rising for over a week, the share of COVID infections ascribed to BA.5 doubled at the end of last month. And according to the US Centers for Disease Control and Prevention (CDC), BA.4 and BA.5 are now most likely the dominant variants in the country, accounting for about 52 percent of new cases in the US, numbers that experts say could rise in the weeks to come.

BA.4 and BA.5 are two newly designated Omicron lineages, meaning they are Omicron viruses with a new combination of mutations. Both were first detected in South Africa – BA.4 in January and BA.5 in February 2022 – and are now the dominant variants there. South Africa performs genetic sequencing on more SARS-CoV-2 samples than many other countries, so it is possible that these variants emerged somewhere else and South African scientists were simply the first to spot them.

New mutations are expected in a virus as widespread as SARS-CoV-2; they occur as the virus divides inside hosts and random errors in the copying of genetic material occur. The more the virus spreads and the more people it infects, the more likely mutations are to arise. Mutations matter only if they enhance the severity of the disease the virus causes, significantly enhance its ability to overcome the immunity provided by vaccines or previous infection, or render diagnostic tests less effective, making it harder to control the spread of the disease.

The fact that BA.4 and BA.5 have quickly become dominant over previous subvariants of Omicron would indicate that they harbour mutations that make them more transmissible, either due to these mutations or due to waning protection from vaccines and previous infections. It is likely a combination of both, although it is too early to say for sure.

The two subvariants are often discussed together because the mutations in their spike protein gene are identical, even though they differ in mutations found elsewhere. The spike protein is key, as this is what the virus uses to infect and enter human cells, and changes here that make the process easier and quicker will make the virus more transmissible. The spike protein is also the part of the virus that is targeted by the majority of COVID-19 vaccines.

The European Centre for Disease Prevention and Control (ECDC) – which regularly assesses new evidence on variants detected through epidemic intelligence, rules-based genomic variant screening, or other scientific sources – has designated the BA.4 and BA.5 subvariants as “variants of concern”, indicating a significant effect on transmissibility, severity and/or immunity that is likely to have an impact on the epidemiological situation in Europe.

Both new variants carry an L452R mutation, which was also previously detected in the Delta variant, and is thought to make the virus more contagious by enhancing the virus’s ability to attach to human cells; it may also help it to partially evade destruction by immune cells. They also possess a genetic change, called an F486V mutation, near where their spike protein binds to human cells. This may also help them partially evade our immune response. They also contain a change in their genetic sequence known as an S-gene dropout, which means they will not show up on certain PCR tests that look for the S-gene to give a positive result.

So far, there is no indication that BA.4 or BA.5 are associated with new symptoms or more severe disease. This is to be expected, given that the majority of mutations are similar to those found in other Omicron lineages, although it is something that will continue to be closely monitored by the World Health Organization (WHO).

Research is still ongoing as to whether the new subvariants can evade protection given by vaccines and/or previous infections from other variants.

One small study showed that antibodies against the BA.2 Omicron were less effective at neutralising the BA.4 and BA.5 subvariants. It also found that antibodies elicited by the COVID-19 vaccines were more effective against these new subvariants than those garnered by the previous infection. Another, yet to be peer-reviewed study found people who were not vaccinated and had been previously infected with the BA.1 subvariant of Omicron were more likely to get reinfected with BA.4 and BA.5 compared with those who had been vaccinated.

What can we do?

Most experts agree that we are likely to see more cases of COVID as a result of the combination of the new subvariants, waning protection, and easing of safety measures.

To prevent healthcare systems from becoming overwhelmed with patients suffering from severe symptoms as a result of infections from these subvariants, it is wise to take precautionary measures.

Many countries are offering a second booster, or fourth dose, to older or at-risk groups of people to top up their protection and protect against severe symptoms. Drug companies are also working on making Omicron-specific vaccines, though these may now need to be tweaked to protect against these new subvariants.

It is good to remember that this virus, regardless of its variants, is airborne. Maintaining airflow and good ventilation indoors, in order to keep air moving, is a good way to reduce your chances of getting infected.

Although many countries have dropped mask mandates, wearing a mask such as an N95 or FFP2 mask in indoor crowded spaces or on public transport is a good way to reduce your risk of getting the virus.

Testing is a key part of monitoring new variants; some countries have scaled back free testing or only made it available to certain groups of people such as health and social care professionals, but in order to keep an accurate track of numbers and variants, we need to consider making testing more readily available.