Thread by @DoctorChrisVT

If you’re worried about the delayed second dose of the COVID vaccines here’s a thread.

I live with my wonderful mother-in-law (below): she is high risk and has had a single dose. She's hoping for another but is worried about a delay. You may feel the same...
#VaccineStrategy

I’ve also received a single dose of the Pfizer vaccine and since COVID gave my identical twin brother a serious heart problem I have a dog in the fight (two dogs including the MiL). I don’t want this virus and I have to go to work in a hospital where there is a lot of it about.

Overall the decision to extend the schedule so there is a 12 week gap between doses should save more lives. Now I’m a nice guy but of course I care more about MY life (and my mother in law's!) than just any old life like yours.

I think there are 3 questions for selfish people like me.

1. How does the delay affect my personal risk of dying (how effective is a single dose)?

2. When should we give a second dose?

3. How does everyone else getting vaccinated protect me better than a double dose?

Question 1: How effective is a single dose? At first glance a single jab with the Pfizer vaccine seems only 52% effective. But most of the people who got the virus became infected very shortly after receiving the vaccine, before an immune response would be expected.

Remember it takes days to weeks for your body to recognise the vaccine and start to produce the cells and antibodies necessary to fight the virus.

If we only look at people who became infected later than 14 days after the first dose it seems around 90% effective. This holds until around 10 days after the second dose (remember the second dose wont start having an effect until then) - roughly a 20 day period.

If you want the numbers there were only 4 COVID cases in this period in the vaccinated group compared to 42 in the placebo group. It’s not certain how long this Pfizer protection lasts for but the Moderna vaccine (not licensed yet but same tech) protects to 108 days.

Are we certain that the Pfizer vaccine will provide protection for this long? No.

Is it a good bet grounded in evidence? Yes.

What seems clear from available data is that short term protection from dose 1 is very high from day 10 after vaccination. nejm.org/doi/full/10.10…

What about the Oxford/AstraZeneca vaccine? It uses different tech: a modified chimpanzee “cold” virus which can’t multiply. It delivers the viral spike genetic code into the cells of the recipient which then make the virus protein which the immune system responds to.

The AZ vaccine efficacy was 73% at 22 days. Unpublished data show it probably protects well for 12 weeks with very high protection against hospitalisation from 21 days after dose 1 until two weeks after the second dose.

This suggests that a single dose will provide high short term protection against severe disease. thelancet.com/journals/lance…

Question 2: when should we give a second dose? It’s likely (I don’t know this so may be corrected) that the interval between doses was compressed because of the urgency of the trials. In general longer intervals give better immune responses! Some vaccines we wait years.

This is for a few reasons but essentially your body gradually makes antibodies which bind the disease with greater strength.
So as a rule, short intervals result in significantly lower booster responses. Example: pediatrics.aappublications.org/content/107/4/…

This may be especially true for the AZ vaccine as you can develop antibodies to this vaccine itself (remember it is a virus that can’t multiply). Allowing these antibodies to reduce may be the reason for improved efficacy of a longer second dose interval.

There is currently no reason to expect that the immune response from the Pfizer vaccine would differ substantially from the AstraZeneca and Moderna vaccines. So again it should give pretty long lasting protection after dose 1.

By now hopefully you’re satisfied that it seems very likely that people will have near full protection until their second dose and as a bonus they’ll get better protection lasting longer from the second dose.

Question 3 for those who'd still like the extra certainty for a second dose: What then are the benefits to me personally from everyone else being vaccinated? Well @AdamjKucharski has written an excellent thread which is relevant here.

https://twitter.com/AdamJKucharski/status/1343567425107881986?s=20

Essentially a more transmissible virus is far worse than a more deadly virus. Widespread vaccination reduces transmission. Even with 2 doses there is some vaccine failure. Vaccinating everyone else protects you even if you're vaccinated.

So this decision seems like a win-win. We are individually and collectively more likely to stay alive this way. Getting vaccinated is selfish and generous all at once!

There are arguments that people didn’t consent to a single dose and that much of the above is speculative. Personally I consented to a level of protection for which there are good data even if my second dose is delayed by a few weeks.

There are some immunological threads out there about single doses leading to quicker vaccine escape. They are largely about lab data not human population data - labs are different evolutionary environment for viruses than human bodies.

It’s a racing certainty the virus will escape the vaccine but doing things this way round should make us all feel a little safer while we keep our distance.

Disclaimer - I’m not vaccine scientist, I'm a molecular virologist and I do give vaccines so can understand the logic used by the Joint Committee on Vaccination and Immunisation - the JCVI - who made the recommendation. Details here - cas.mhra.gov.uk/ViewandAcknowl…