The omicron sub-variant known as BA.5 was first discovered in South Africa in February 2022 and spread rapidly throughout the world. As of the second week of July 2022, BA.5 was compiled nearly 80% of COVID-19 variants in the United States.
Soon after, researchers in South Africa reported on original version omicron variant (B.1.1.529) on Nov 24, 2021 many scientists – myself included – have speculated that if omicron’s multiple mutations make it either more portable or better at evading immunity than the previous delta variant, omicron may become the dominant variant worldwide.
The omicron variant really did dominant in early 2022, and since then several omicron sublines or subvariants have appeared: BA.1, BA.2, BA.4, and BA.5, among others. With the continued emergence of such highly transmissible variants, it is apparent that SARS-CoV-2, the virus that causes COVID-19, is effectively using classic techniques that viruses use to escape the immune system. These escape strategies range from changing the shape of key proteins recognized by your immune system’s protective antibodies to camouflages its genetic material to trick human cells into thinking of it as part of themselves instead of an invader to attack.
I am virologist which studies emerging viruses and viruses that have jumped from animals to humans, such as SARS-CoV-2. My research group is tracking the transmission and evolution of SARS-CoV-2, assessing changes in how well omicron subvariants evade the immune system and the severity of disease they cause after infection.
How is transmissibility of the virus measured in the population?
After some individuals in a population become immune due to previous infection or vaccination, epidemiologists use the term effective reproductive number, called Re or Rt, to measure the transmissibility of the virus. Re of the omicron variant is estimated at 2.5 times higher than the delta option. This increased transmissibility most likely helped the omicron overtake the delta to become the dominant option.
The bigger question then is what drives the evolution of the omicron sublines? The answer to this is a well-known process called natural selection. Natural selection is an evolutionary process in which traits that give a species a reproductive advantage continue to be passed on to the next generation, while traits that do not are gradually eliminated through competition. As SARS-CoV-2 continues to circulate, natural selection will favor mutations that give the virus the greatest survival advantage.
What makes the omicron and its offshoots so hidden in propagation?
Several mechanisms contribute to the increased transmissibility of SARS-CoV-2 variants. One is the ability to bind more strongly to the ACE2 receptor, a protein in the body that primarily helps regulate blood pressure, but can also help SARS-CoV-2 enter cells. Newer omicron sublines have mutations that make them better at evading antibody protection while retaining the ability to bind effectively to ACE2 receptors. The BA.5 subline can avoid antibodies both from vaccination and previous infection.
Omicron sublines BA.4 and BA.5 share several mutations with earlier omicron sublines, but also have three unique mutations: L452R, F486V and reversion (or lack of mutation) of R493Q. L452R and F486V in the spike protein help BA.5 escape from antibodies. Also, the L452R mutation helps the virus connect more effectively to the membrane of its host cell, a crucial feature related to the severity of the COVID-19 disease.
While the other mutation in BA.5, F486V, may help the subline escape certain types of antibodies, it may reduce its ability to bind to ACE2. Strikingly, BA.5 appears to compensate for the reduced binding strength of ACE2 by another mutation, the R493Q reversion, which is thought to regains its lost affinity for ACE2. The ability to successfully evade immunity while maintaining its ability to bind to ACE2 may potentially have contributed to the rapid global spread of BA.5.
In addition to these immune-evading mutations, SARS-CoV-2 evolved to suppress the innate immunity of their hosts – in this case humans. Innate immunity is the body’s first line of defense against invading pathogens, made up of antiviral proteins that help fight viruses. SARS-CoV-2 has the ability to suppress the activation of some of these key antiviral proteins, meaning it is able to effectively overcome many of the body’s defenses. This explains the spread of infections among vaccinated or already infected people.
Innate immunity exerts strong selective pressure on SARS-CoV-2. Delta and omicron, the two most recent and highly successful variants of SARS-CoV-2, share several mutations this may be key to helping the virus disrupt innate immunity. However, scientists still don’t fully understand what changes to BA.5 might allow it to do this.
BA.5 will not be the end game. As the virus continues to circulate, this evolutionary trend is likely to lead to the emergence of more transmissible variants that are capable of immune escape.
Although it is difficult to predict what variants will emerge next, we researchers cannot rule out the possibility that some of these variants will lead to increased disease severity and higher hospitalization rates. As the virus continues to evolve, most people will get COVID-19 repeatedly despite vaccination status. This can be confusing and frustrating for some and can contribute to vaccine hesitancy. Therefore, it is important to recognize that vaccines protects against serious illness and deathnot necessarily from infection.
Research over the past two and a half years has helped scientists like me learn a lot about this new virus. However, many questions remain unanswered because the virus is constantly evolving and we are left trying to navigate a constantly moving door. While updating vaccines matching circulating variants is an option, it may not be practical in the short term because the virus evolves too quickly. Vaccines that generate antibodies against a wide range of SARS-CoV-2 variants and a cocktail of comprehensive treatmentsincluding monoclonal antibodies and antiviral drugs, will be critical in the fight against COVID-19.