New COVID Omicron Variant Spreads BA.4 and BA.5 Have Become Dominant
The most recent subvariants of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), BA.4 and BA.5, have caused significant upsurge in new cases and hospitalizations in many countries around the world. Soon after their initial discovery in South Africa, BA.4 and BA.5 subvariants have been detected throughout the world. These variants have already caused outbreaks in South Africa and Portugal and is currently leading to major jumps in new cases and hospitalizations in many parts of Europe, including the UK, France, Germany, Italy, and Greece. Especially BA.5 subvariant has rapidly grown dominant across Europe and the US. According to the latest estimates by the Centers for Disease Control and Prevention (CDC), as of July 9, BA.5 subvariant is responsible for around 65% of all cases in the US. However, the impact of the new subvariants are not exclusive to Europe and the US. The recent upsurge in new cases experienced elsewhere, such as New Zealand and Malaysia, is being linked to BA.4 and BA.5 subvariants. How do the Omicron BA.4 and BA.5 subvariants differ from previous lineages of SARS-CoV-2 and what is behind their rapid rise to dominance around the world? Read along to learn more about the BA.4 and BA.5 subvariants, their infectivity, pathogenicity, and ability of immunity evasion, along with effectivity of current tests and vaccines against these new subvariants.
What are Omicron BA.4 and BA.5 subvariants?
Viruses continuously evolve through mutations that occur during their replication process. When a virus acquires a sufficient amount of distinct mutations, it may be referred to as a new variant. In cases where the alterations may be less major, the virus may be categorized as a subvariant. The BA.4 and BA.5 subvariants were detected in January and February 2022 in South Africa. The data has demonstrated that BA.4 subvariant shares all but eight mutations/deletions with the BA.2 lineage. Similar to its sibling BA.4, the BA.5 subvariant carries several mutations that distinguish it from previous versions of the virus. Most mutations of the BA.4 and BA.5 subvariants are located in the spike protein, which facilitates viral entry and binding. Indeed, some of the significant mutations shared by the BA.4 and BA.5 include F486V and L452R mutations in the spike protein, both of which have been linked to increased infectivity, pathogenicity, and immune escape. Moreover, both subvariants have a 69/70 deletion in their spike protein, which creates a shortcut or the identification of the subvariant by causing an S-gene target failure.
Are Omicron BA.4 and BA.5 subvariants more infectious than previous variants?
So far, clinical and epidemiological data suggest that the BA.4 and BA.5 subvariants may be 10% to 15% more infectious relative to previous subvariants of the Omicron strain. Still, the rapid rise to dominance of the BA.5 subvariant has been linked primarily to an enhanced ability to evade neutralizing antibodies produced by recovery or vaccination. The antigenic distance of the BA.4 and BA.5 subvariants reduce our recognition of and immune response to the spike protein of the virus, which significantly increases the risk of reinfection. Accordingly, several studies have found BA.5 and BA.4 subvariants to be the most immune-evasive among Omicron lineages with low levels of neutralizing antibody responses. The BA.5 subvariant has also been observed to display superior fitness, which combines multiple parameters including lineage growth, reproduction number, level of immune-evasion and generation time.
Are Omicron BA.4 and BA.5 subvariants cause more severe disease than previous variants?
According to the European Centre for Disease Prevention and Control (ECDC), neither BA.4 nor BA.5 subvariant appears to induce more severe disease. However, one experimental study by Kimura et al. (2022), which has not yet been peer-reviewed, has demonstrated that compared to BA.2 subvariant, both BA.4 and BA.5 spread more efficiently in human lung cell cultures and were more pathogenic in Syrian hamsters.
Are the symptoms of Omicron BA.4 and BA.5 subvariants different from previous variants?
There is currently no evidence to suggest a difference in COVID-19 symptoms for the BA.4 and BA.5 subvariants. Especially in fully vaccinated people, the BA.4 and BA.5 subvariants, similar to other Omicron lineages, typically cause symptoms resembling the common cold such as nasal congestion, sore throat, cough, fever, muscle pain, and fatigue. Loss of taste and smell appears to be less common in people infected with Omicron variants, whereas back pain is becoming a more common symptom. In fact, according to the ZOE Health Study, as of February 10, 2022, around 20% of the people infected with Omicron experienced back pain. It should also be noted that as the circulation of the BA.4 and BA.5 subvariants increase the risk of breakthrough infections, the risk of developing long COVID or more serious complications such as diabetes, cognitive impairment, heart attack, and stroke increases with each reinfection with SARS-CoV-2.
Are vaccines still effective against Omicron BA.4 and BA.5 subvariants?
Despite the increased ability of the BA.4 and BA.5 subvariants to bypass immunity induced by previous infections and vaccination, staying up to date with vaccines remains crucial for the prevention of severe disease and death regardless of the variant. Indeed, although research at the Africa Health Research Institute has demonstrated that antibodies elicited by vaccinated individuals were significantly more effective against BA.4 and BA.5 relative to those induced solely by recovery. Moreover, according to Centers for Disease Control and Prevention (CDC), as of April 2022, unvaccinated people aged 5 years and older were 6 times more likely to die from COVID-19 compared to those vaccinated with at least a primary dose of vaccine. For unvaccinated people aged 50 and older, the risk of death from COVID-19 were 42 times higher than those vaccinated with at least a primary series and two booster doses. These figures also illustrate the efficacy of booster shots alongside primary vaccination. In fact, among people aged 50 and older, risk of death for those vaccinated with a primary series and one booster shot were 4 times higher compared to people vaccinated with a primary series and two or more booster shots.
Are Rapid Antigen Test Kits still effective in the diagnosis of Omicron BA.4 and BA.5 subvariants?
There are currently no studies on the sensitivity, specificity, and accuracy of diagnostic tests in the diagnosis of the BA.4 and BA.5 subvariants. However, since these methods target the viral genome and involve amplification techniques, molecular assays such as the polymerase chain reaction (PCR) tests remain highly accurate regardless of the version of SARS-CoV-2. On the other hand, because the majority of the mutations carried by the BA.4 and BA.5 subvariants are found in its spike protein, the performance of rapid antigen tests targeting the SARS-CoV-2 spike protein may be affected. However, the sensitivity, specificity, and overall accuracy of rapid antigen tests targeting the nucleocapsid protein, such as the RapidFor™ SARS-CoV-2 Rapid Antigen Test Kit, are significantly less likely to be affected by the mutations of the BA.4 and BA.5 subvariants.
- Khan, K., Karim, F., Ganga, Y., Bernstein, M., Jule, Z., Reedoy, K., Cele, S., Lustig, G., Amoako, D., Wolter, N., Samsunder, N., Sivro, A., San, J. E., Giandhari, J., Tegally, H., Pillay, S., Naidoo, Y., Mazibuko, M., Miya, Y., . . . Sigal, A. (2022). Omicron sub-lineages BA.4/BA.5 escape BA.1 infection elicited neutralizing immunity. medRxiv. https://doi.org/10.1101/2022.04.29.22274477
- Kimura, I., Yamasoba, D., Tamura, T., Nao, N., Oda, Y., Mitoma, S., Ito, J., Nasser, H., Zahradnik, J., Uriu, K., Fujita, S., Kosugi, Y., Wang, L., Tsuda, M., Kishimoto, M., Ito, H., Suzuki, R., Shimizu, R., Begum, M. M., . . . Sato, K. (2022). Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5. bioRxiv. https://doi.org/10.1101/2022.05.26.493539