New data on AstraZeneca vaccine:

What’s the same, what’s new and what we still don’t know

Yesterday (2^nd February) the Lancet released a non-peer-reviewed publication on further analysis evaluating the results from the use of the AstraZeneca vaccine. I believe some of the media coverage was misleading!

Data were provided which address 3 specific questions:

What is the level of protection after one dose of the vaccine?
What is the evidence to support the (UK) recommended interval of 3 months between doses?
How effective is the vaccine at preventing transmission of the infection?

In this post I briefly summarise what we knew before these results, consider what has changed and what we still need to know or have confirmed.

(Readers may be aware that yesterday also saw the publication of a paper from the Russian ‘Sputnik’ vaccine team. Their results are very relevant given the close similarity between the AstraZeneca and the Russian vaccines. I will discuss these in further post later this week!)

What do we mean by protection?

It is really important to be clear what is meant by the term ‘protection’ and how we interpret expressions such as ‘60% protection’. I have defined this before, but it is worth repeating here.

Firstly, vaccines report their success at reducing outcomes of varying impact

Secondly, any percentage for any of these outcomes refers to a comparison with an identical group of people who were not vaccinated
This can only come from a clinical trial where there was such a comparison group
Thus, a vaccine that has 60% protection against being admitted to hospital means that in the clinical trial there were 60% fewer admissions in the groups who had been vaccinated compared to those who had the dummy vaccine
Further, it is hard to assess the significance of some of the percentages reported as they are based on small numbers of cases

What did we know before the recent results?

The authors repeated yesterday the results that had already been published at the time of licensing the vaccine and discussed in previous posts. These all refer to the protection analysed 14 days after the second dose: in brief these were:

We also already knew, again as I discussed in a previous post

The vaccine gives good antibody protection after one dose, but this wanes after about a month
A second dose maintains that initial protection
The greater the interval between doses, the greater the protection in terms of people reporting symptoms, reaching 80% with a 12-week gap

The new data

What is the level of protection after one dose of the vaccine?

In this new analysis the researchers took advantage of the fact that:
- Some of the people in their trial had a 3 month interval between doses
- Some people dropped out after one dose
They compared the number of cases occurring in the active vaccine and the placebo groups, in the period from 3 weeks to 3 months after the first dose
Each group had about 9250 volunteers
For simplicity I have shown the values as the number of cases rather than rates/1000 people

Let me explain this graph:
Looking at the first two bars on the left
- In those who had the active vaccine there were 17 cases with symptoms
- In those who had the placebo there were 71 cases with symptoms
- This means a 76% reduction of symptomatic cases in that 3 week to 3 month interval
The second two bars show there was no reduction in asymptomatic cases
The third set of two bars show that by combining both symptomatic and asymptomatic cases, the overall reduction was 67%

Summary

There is indeed protection against developing infection with symptoms in the period between 3 weeks and 3 months after the first dose.
This is important! These data show that whilst waiting for a second dose there is good protection against being ill, they do not show that a second dose is not needed.
Remember that without a second dose the level of antibodies does fall and hence it is unlikely that this level of protection would be maintained

What is the evidence to support the (UK) recommended interval of 3 months between doses?

Here a very different question is being addressed:

“In those who had two doses, how much does the interval between doses affect the level of protection for the period starting 14 days after the second dose?”

The volunteers were followed up, depending on when they were recruited, for up to 6 months after the second dose
This is what the data showed:

Again let me explain:
- from the left-hand bar: if the interval between first and second dose was between 3 to 6 weeks, then the people who had the active vaccine had 54% fewer cases with symptoms than those who had the dummy vaccine
- from the right-hand bar: If the interval between first and second dose was longer than 11 weeks then the people who had the active vaccine had 82% fewer cases with symptoms

Summary:

The longer the delay the greater the protection after the second dose.
This is the same as the conclusion from the earlier study, the difference being that they now have up to 6 months of follow up data compared to only around 2 months in the first report.
This reinforces the message that for this vaccine a 3 month delay is if anything beneficial

How effective is the vaccine at preventing transmission of the infection?

This third question is really relevant to considering the issue of herd immunity.
We want the vaccine to reduce the number of people who can spread the infection, which means reducing both those with and without symptoms.
The data from people who just had one dose of the vaccine (the middle two bars in the first graph of this blogpost) showed no reduction in the number of people who have asymptomatic infection
I have also looked at the data for people who have had two doses
Looking at who developed an asymptomatic infection, the numbers were identical: 41 who had the active vaccine and 42 who had the placebo
We also need to consider the combined number of both symptomatic and asymptomatic cases

Summary:

Overall there is a large reduction in the combined number of symptomatic and asymptomatic cases
The virus of course can be transmitted by both symptomatic and asymptomatic cases
Whilst the vaccine reduces the number who can transmit the virus after becoming ill, it does not reduce the number who do so with a ‘silent infection’
I think the media reports may have been misleading here

We also still don’t know:

As per my post last week – whether these results apply to the over 65’s: they may, we don’t know
We also don’t know how these results will apply to the new variants of the virus, as the data were gathered before these variants were widespread
Half the participants were actually in South Africa or Brazil, but whether the cases that developed in the participants came from the new variants was not investigated

Conclusions

My views on the AstraZeneca vaccine have not really been changed by these new data
It is good that the first dose gives some protection whilst people wait for their second dose
It is also reassuring that the data support the suggested interval in the UK of 3 months between doses
The results do not detract from the positive fact that there were no severe cases in the active vaccine group
However as there were only 3 such cases in the placebo group, there are only limited conclusions that can be drawn from that comparison
This headline from AstraZeneca’s press release may need to be interpreted with these data in mind
And “yes” I would still have this vaccine!

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