Australia heads for its third Omicron wave in the coming weeksas BA.4 and BA.5 become the dominant COVID strains†
BA.4 and BA.5 are more contagious than previous COVID variants and subvariants, and are better able to evade immunity from vaccines and previous infections. So we will probably 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 subvariants (i.e. a group of viruses of the same parent virus), all of which will appear in South Africa at the end of November 2021: BA.1, BA.2, and BA.3.
The three are genetic different enough that they could have had their own Greek names. But for some reason this didn’t happen and the World Health Organization labeled 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 over 100,000 per day.
However, BA.2 is even more transmissible than BA.1, and Australia saw a second wave of cases, this time caused by BA.2. This wave peaked in early April with more than 60,000 cases per day.
When were BA.4 and BA.5 detected?
BA.4 was first detected in January 2022 in South Africa. BA.5 was also detected in South Africa in February 2022.
Both appear to be offshoots of BA.2, which share many identical mutations. They also have many additional mutations that likely affect transmission.
They are discussed together because mutations in their spike protein (the bit that clings to human cells) are identical. (For brevity I call them BA.4/5.)
However, they differ in some of the mutations on the virus’s body.
How transferable is BA.4/5?
We measure how contagious a disease is based on the basic reproduction number (R0). This is the average number of people who infect a first case in a population without immunity (from vaccines or previous infection).
New mutations give the virus an advantage if they can increase transmissibility:
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the original Wuhan strain has an R0 of 3.3
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Delta has an R0 of 5.1
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Omicron BA.1 has an R0 of 9.5
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BA.2, which is currently the dominant subvariant in Australia, is 1.4 times more transferable than BA.1, and thus has an R0 of about 13.3
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a pre-print publication from South Africa suggests that BA.4/5 is a . has growth advantage above BA.2 comparable to the growth advantage of BA.2 over BA.1. That would give it an R0 of 18.6.
This is similar to the measleswhich was our most contagious viral disease to date.
How likely is reinfection?
BA.4/BA.5 seem to be masters of dodge immunity. This increases the chance of reinfection.
Reinfection is defined as a new infection at least 12 weeks after the first. This gap is there because many infected people are still releasing virus particles many weeks after recovery.
However, some unlucky people get a new infection within 12 weeks and are therefore not counted.
There are probably dozens now thousands of Australians in their second or third infection, and this number will only increase with BA.4/5.
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How high are case numbers likely 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, given the immunity in the population.
All Australian states and territories now have a Reff greater than one meaning that even with current levels of immunity we are seeing exponential growth in the number of cases. This will inevitably lead to an increase in hospitalizations and deaths.
The second Omicron wave due to BA.2 was not as high as the first caused by BA.1, probably because so many people were infected with BA.1 that the subsequent immunity dampened the second wave.
This third wave may not be as high as the second for the same reason.
How severe is the disease from BA.4/5?
A recent pre-print publication (a publication not yet peer-reviewed) by a Japanese research group found that BA.4/5 in laboratory-based cell culture experiments was able to replicate more efficiently in the lungs than BA.2. In hamster experiments, it developed into a more serious disease.
However, data from South Africa and the United Kingdom found that their BA.4/5 wave did not see a major increase in serious illness and death.
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This may be due to the high level of immunity resulting from previous infections.
Our high vaccine-induced immunity may have a similar protective effect here.
Will BA.4/5 change long-term COVID?
At this stage, we don’t know if any of the Omicron subvariants differ in their ability to cause long-term COVID.
We do know that full vaccination (three doses for most people) does offer some protection against long-term COVID.
How protective are our vaccines against BA.4/5?
Each new sub-variant of Omicron has been able to evade immunity from vaccination better than its predecessor.
While current Wuhan-strain vaccines will still provide some protection against serious illness and death from BA.4/5, they are unlikely to provide little or no protection against infection or symptomatic disease.

What about new vaccines?
The good news is that second-generation vaccines are in clinical trials. moderna tests a vaccine containing mRNA against the original Wuhan strain and Omicron BA.1.
The first results are promising and probably give a much better protection against BA.4/5.
But this third Omicron wave — along with a very severe flu season — is likely to cause even more trouble for our hospitals in the coming weeks.
If things get bad enough, state and territory governments in many environments could be forced to reintroduce face mask mandates — not such a bad thing in my opinion.

Adrian Esterman is Professor of Biostatistics and Epidemiology at the University of South Australia. This piece first appeared on The conversation†
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