BA.4 and BA.5 are more virulent than previous variants and sub-variants of Covid and are better able to evade immunity from vaccines and previous infections. So we are likely to see an increase in the number of cases. So what are BA.4 and BA.5? And what can we expect in this next phase of the pandemic?
How did it start? BA.1, BA.2 and BA.3
Omicron started as three sub-variants (ie a group of viruses from the same parent virus) that all appeared in late November 2021 in South Africa: BA.1, BA.2 and BA.3. The three are genetically different enough that they could have had their own Greek names. But for some reason, this did not happen and the World Health Organization classified them as sub-variants of Omicron. BA.1 quickly took over from Delta in Australia in early January this year, forming a massive wave of cases, peaking at more than 100,000 a day. However, BA.2 is even more contagious than BA.1, and Australia saw a second wave of cases, this time caused by BA.2. This surge peaked in early April with more than 60,000 cases per day. The first and second Omicron waves peaked in early January and early April. Photo: Covid19data.com.au
When were BA.4 and BA.5 detected?
BA.4 was first spotted in January 2022 in South Africa. BA.5 was also spotted in South Africa in February 2022. Both appear to be offshoots of BA.2, sharing many identical mutations. They also have many additional mutations that may affect transmission. They are discussed together because the mutations in their spike protein (the part that sticks to human cells) are identical. (For brevity, I refer to them as BA.4/5.) However, they differ in some of the mutations in the body of the virus.
How contagious are BA.4/5?
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 without 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 the dominant subvariate in Australia at the moment, is 1.4 times more contagious than BA.1, and thus has an R0 of about 13.3 a preprint from South Africa suggests that BA.4/5 has a growth advantage over BA.2 similar to the growth advantage of BA.2 over BA.1. This would give him an R0 of 18.6.
This is similar to measles, which until now has been our most contagious viral disease.
How likely is reinfection?
BA.4/BA.5 seem to be masters at avoiding immunity. This increases the chance of re-infection. Reinfection is defined as a new infection at least 12 weeks after the first. This gap exists because many infected people are still shedding virus particles many weeks after recovery. However, some unlucky people get a new infection within 12 weeks and are therefore not counted. Likely, there are now tens of thousands of Australians on their second or third infection and that number will only get bigger with BA.4/5. A woman wearing a protective face mask stands outside the international terminal at Sydney Airport. One study found that BA.4/5 can replicate more efficiently in the lungs than BA.2. Photo: Loren Elliott/Reuters
How likely are case numbers to rise?
Around Australia, we are starting to see a third wave of cases due to BA.4/5. The effective reproduction number, or Reff, tells us, on average, how many people an infected person will pass it on to, given immunity in the population. All Australian states and territories now have a Reff greater than 1, meaning that even with current levels of immunity, we are seeing an exponential increase in case numbers. This will inevitably lead to increased hospitalizations and deaths. The second Omicron wave due to BA.2 was not as high as the first one caused by BA.1, possibly because there were so many people infected with BA.1 that the ensuing immunity limited the second wave down . This third wave may not be as high as the second for the same reason.
How severe is BA.4/5 disease?
A recent preprint (one that has not yet been peer-reviewed) by a Japanese research group found that in laboratory-based cell culture experiments, BA.4/5 was able to replicate more efficiently in the lungs than BA.2. In experiments with hamsters, it developed into a more severe disease. However, data from South Africa and the UK found that their BA.4/5 wave did not see a significant increase in serious illness and death. This is probably due to high rates of immunity due to previous infections. High rates of vaccine-induced immunity may have a similar protective effect here.
Will BA.4/5 change long Covid?
At this stage, we do not know if any of the sub-variants of Omicron differ in their ability to cause long-lasting Covid. However, we do know that full vaccination (three doses for most people) provides some protection against long-term Covid. A South Australian government campaign poster at a bus shelter in Adelaide on June 24 urges people to get their third Covid vaccine. Photo: Amer Ghazzal/Rex/Shutterstock
How protective are our vaccines against BA.4/5?
Each new sub-variant of Omicron has been better at avoiding vaccination immunity than its predecessor. Although current vaccines based on the Wuhan strain still provide some protection against severe disease and death against BA.4/5, they are unlikely to provide much, if any, protection against infection or symptomatic disease.
What about new vaccines?
The good news is that second-generation vaccines are in clinical trials. Moderna is testing a vaccine containing mRNA against the original Wuhan strain and Omicron BA.1. Early results are promising and likely to offer much better protection against BA.4/5. But this third wave of Omicron – along with a very severe flu season – will likely see our hospitals struggle even more in the coming weeks. If things go badly enough, state and territory governments may be forced to reinstate face mask mandates in many settings – not so bad in my opinion.
Adrian Esterman is a professor of biostatistics and epidemiology at the University of South Australia This article was originally published on Conversation.
