Clearer picture of long-term vaccine efficacy against severe COVID

It has already been established – with reasonable certainty – that the power of COVID-19 vaccines to protect against symptomatic infection declines with time.
 
Now, pre-print studies in England and the United States are offering a broader – mostly reassuring – picture about the vaccines’ ability to protect recipients against severe illness and death.
 
Of most relevance to the Australian rollout is a pre-print study from Public Health England (PHE), which analysed the capacity of the Pfizer, AstraZeneca and Moderna COVID-19 vaccines to prevent mild and severe illness from 8 December last year to 3 September 2021.
 
It reports a ‘limited waning’ in the vaccines’ ability to prevent hospitalisation beyond 20 weeks after a second dose.
 
Protection against symptomatic disease caused by the Delta variant peaked in the first weeks after the second dose, then fell to 47.3% and 69.7% beyond 20 weeks for AstraZeneca and Pfizer respectively. The study suggested efficacy declined more steeply for those aged over 65.
 
Researchers recorded AstraZeneca’s level of protection against hospitalisation at 20 weeks after vaccination as 77%, with Pfizer registered as 92.7% in the same timeframe. The protection efficacy against death was 78.7% and 90.4% for AstraZeneca and Pfizer respectively.
 
As the Moderna vaccine was introduced later in the rollout in the UK, there was not enough data to gauge its longer-term efficacy against hospitalisation. However, it appeared to offer the highest level of protection against symptomatic infection with efficacy rates of 94.8%.
 
In the United States meanwhile, a non-peer reviewed study published last week by the Centers for Disease Control and Prevention (CDC) compared efficacy for the two existing mRNA vaccines as well as the Johnson & Johnson option – the latter of which is not available in Australia.
 
The research, which included data for 21 hospitals in 18 different states and focused on non-immunocompromised adults, indicated the mRNA vaccines offered the strongest protection.
 
Overall safeguarding rates against hospitalisation for the March to August study period stood at 93% and 88% for Moderna and Pfizer respectively. However, Pfizer efficacy is reported as fading more rapidly after 120 days to 77%, while Moderna recorded a higher level of efficacy at that stage at 92%.
 
Associate Professor Paul Griffin, an infectious diseases physician at the University of Queensland, said the results are encouraging.
 
‘It’s great to see evidence that shows vaccines are providing good levels of protection,’ he told newsGP.
 
‘We are seeing more evidence that immunity does wane over time. But even though we see a relative reduction around the four-to-six-month mark, it’s still relatively modest and we’d still expect high rates of protection even out to that sort of time frame.’
 
Of the differing levels of long-term protection against severe disease reported for the mRNA vaccines in the US study, Associate Professor Griffin does not feel enough evidence yet exists for firm conclusions.
 
‘For every study that shows one is better than the other, there are others that tell you it’s the other way round,’ he said. ‘Practically speaking, the protection is still very similar.’
 
More evidence still required
It is a message echoed by Dr Sean Stevens, a member of the RACGP’s COVID Working Group.
 
‘The jury’s still out [on the relative efficacy of the mRNA vaccines],’ he told newsGP.
 
‘Back at the beginning of the pandemic, we were saying that if we can get a vaccine with 50% or higher efficacy, then we would be happy.
 
‘We’ve got well over that. I think we are in a very good position.’
 
The PHE authors also said the results were reassuring but highlighted the risk for more vulnerable groups.
 
‘Waning was greater in older adults and those in a clinical risk group, suggesting that these individuals should be prioritised for booster doses,’ they wrote.
 
Several limitations are mentioned for both the PHE and the CDC studies. For example, the PHE analysis acknowledges the AstraZeneca vaccine was widely employed among more vulnerable older people, including those in aged care homes – a factor that is also at play in Australia.
 
The study published by the CDC also does not include any data on fatalities due to COVID-19. The corresponding author for the CDC study, Dr Wesley Self of the Vanderbilt University School of Medicine, told newsGP more information on the protection offered against death will be published in the next few weeks.
 
Both articles add to a rapidly evolving understanding of vaccine efficacy, which includes a recent Israeli study that concluded immunity wanes in all age groups the more time elapses after vaccination. There are, however, concerns over potential confounding factors in this study.
 
The CDC study authors also acknowledge that while vaccine efficacy results were adjusted for potential confounders, ‘residual confounding is possible’.
 
Another up-to-date Israeli pre-print analysis has also pointed to much higher rates of protection among the elderly after a third dose of Pfizer.
 
For Dr Stevens, however, the booster discussion remains premature in Australia.
 
‘[Having boosters] is an area that does need further study,’ he said. ‘There will be [future] vaccines that will target variants on the spike protein – it may well be we get boosters but with completely different vaccines, ones that are not even on the market yet.’
 
He believes the focus needs to remain on the current rollout out for now.
 
‘I think the most important thing is for people to get vaccinated with whichever vaccine they can get access to,’ he said.
 
‘Any of them is better than none. We really need to get protected, then we can work out where to go once the whole population has been vaccinated.’
 
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