BA.5 confirmed as dominant strain in Australia

On 11 July, 46.4% of all COVID cases in Australia were estimated to be BA.5, according the latest Department of Health Primary Care COVID-19 update.
 
The new variant, dubbed a ‘master at evading immunity’ and ‘the worst’ to have emerged to date, is driving a new wave of cases across the country that has seen hospitalisations increase by 63% in the past month alone.
 
And while already acknowledged as the most infectious strain since the pandemic began, a new Kirby Institute pre-print has now revealed more information on the potential impact BA.5 may have.
 
The paper shows that BA.5 is more likely to target the lower respiratory system than other Omicron variants – in a manner more akin to Delta than BA.1 or BA.2 – and that monoclonal antibody therapies like Evusheld and Sotrovimab will probably be less effective.
 
However, while BA.5 may impact these treatments, co-author Associate Professor Stuart Turville told newsGP three doses of COVID vaccine appear to provide good protection against severe disease and that oral antivirals should still work.
 
‘As a virologist, BA.5 is certainly the most interesting of the Omicron family,’ he said.
 
‘To sum up what we see, antibodies in the community – from vaccination or vaccination plus infection – still bind and block the virus, but at levels lower than the earlier variants, which is typical for all Omicron lineages in general.
 
‘[Monoclonal antibody treatments] are still binding and inhibiting the virus, but at levels 14.3-fold lower using Evusheld and 16.8-fold lower using Sotrovimab compared to the original virus.
 
‘[However], the use of drugs that target the virus from within the cell [Paxlovid and Lagevrio] will get around the continued changes to the virus spike.’
 
Associate Professor Turville also cautioned against attributing the higher infection rate purely to BA.5’s ability to evade antibodies, saying it could potentially be due to an ability to infect cells better on a per virion basis.
 
‘We are seeing a signal that BA.5 can infect our body a little differently than its other Omicron relatives … in a manner that is similar to pre-Omicron variants,’ he said.
 
‘It can have the benefit of its parent BA.2 – great at transmission and very slippery to existing antibodies – but also has expanded its options into what cells it likes.
 
‘It uses a protein called TMPRSS2 better and use of that protein increases its efficiency of infecting cells lower in the respiratory tract.
 
‘Other Omicrons didn’t do that so well. This one does.’
 
He also pointed out that in animal models, disease severity is higher and the lung is more of a viral target, but notes that this does take into account prior viral infection and/or vaccination.
 
‘If we try to predict the outcome, many are modelling that we will see a global wave, but probably closer to a BA.2 wave [not as large as BA.1], and countries with high vaccine uptake and/or high levels of previous infection will weather the storm,’ he said.
 
‘We may continue to see a signal of concern with increased hospitalisation, but nothing like what we saw early on in the pandemic.
 
‘The key is, the community – thanks primarily to vaccination and good booster uptake – has the immunological experience now to take the edge off disease severity, even with evasive variants like Omicron BA.5.’
 
However, the outcomes are less clear for the nearly 30% of eligible Australians who have not yet received a COVID-19 booster shot.
 
‘As we enter this wave, unfortunately we will find out soon what the benefits of those with third and fourth vaccine doses have, and also many that may have been boosted and then infected in the BA.1/BA.2 waves,’ Associate Professor Turville said.
 
‘One way to see it is that vaccine efficacy after two doses to Omicron BA.1 was low 30% when it turned up in South Africa. In our studies we saw data that predicted the same.
 
‘You just don’t have the potency and breadth in your antibody responses after two doses of either AstraZeneca or Pfizer.’
 
Looking overseas, the outcomes appear to vary. In South Africa, where BA.5 originated, hospitalisations were not as pronounced as when Omicron first emerged.
 
But, in other countries that are now experiencing significant BA.5 waves – such as the US and much of western Europe – hospitalisations are still climbing.
 
Prominent US-based physician Dr Eric Topol, who cited the Kirby Institute pre-print as taking the understanding of BA.5 ‘a step further’, suggests some of this difference may be due to the previous presence of the Beta variant in South Africa compared to other countries.
 
‘There were marked differences between South Africa and Portugal, the first two countries with BA.4/5 case spikes,’ he wrote.
 
‘While that may be attributed to difference in demographics and prior infections, I think it is intriguing that the Beta variant, which hit South Africa very hard and was barely seen in Europe and the US, seems to provide more protection versus Omicron variants than other previous strains.
 
‘While BA.4/5 has already fully descended in those two countries, BA.5 hasn’t yet peaked in many countries.’
 
Regardless of the potential for different outcomes, Dr Topol cautions that more needs to be done to ‘get ahead’ of the virus with second generation vaccines and treatments.
 
‘There’s clearly more room for the virus to evolve, get more fit, gain advantages as an immune escape artist and more efficiently infect cells,’ he said.
 
‘We are watching its accelerated evolution akin to the behaviour of a Formula One race car lapping around the track with humans in the stands.
 
‘At best, there will not be a BA.5 specific booster until November or December and that represents a failed strategy of variant-chasing, knowing full well that BA.5 will not be the dominant circulating virus in 5–6 months.
 
‘We need to get ahead of the virus, [and] stop acting as bystanders with “hope and prayers” that it will not get worse than what we are dealing with now.
 
‘BA.5 has taught us once again, the virus doesn’t just get milder and fade away.’
 
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