C19 Vaccinations – how many do you need and what if you’ve already had Covid19?

Summary

• Giving more people a single dose as a priority and delaying the booster has been a success

• Evidence also suggests that people who have had COVID19 do well after just one dose of vaccine.

• Those who have had COVID19 infections may also have more side effects from the vaccine

• France has now made it policy that those with proven COVID19 only have a single dose.

• This may help roll out the vaccine to the wider population and the world, though the omens are not good

Introduction

The first person I heard talking of giving a single dose of vaccine to twice as many people rather than follow the manufactures recommendations was from, would you believe, Tony Blair. Back in December he first publicised the idea in the Independent. Im pretty sure it wasn’t his original idea, but like all politicians he grabbed the opportunity to make headlines.

Quite a few scientists shouted a loud “Whoa be careful!” For them it went against the grain. With MMR, for example, a single dose protected 60% of recipients, but climbed to 96% after the second dose. Pfizer could only offer advice on the basis of trial results based on their two dose regime three weeks apart and were not best pleased. Astra Zeneca had some results on a trial sub-set which were more encouraging.

Despite these reservations, the idea soon became UK policy on the basis that a little less protection for twice as many people = more protection overall. It might have seemed, as before, that policy was again being scribbled on the back of a chequebook, but given the climbing prevalence of COVID19 in December, is was a good call and has turned out to be the right one. While it’s hard to disentangle the effect of the vaccine programme from the effect of lockdown measures, viral behaviour and community immunity, the descent in hospital admissions has been sharp.

UK Hospital admissions to date – down the third wave.

Jab now – booster later?

One year after the virus has hit our shores, my turn for the vaccine has come. Vaccine hesitancy rates are very low in the UK and in my age group.

According to the Lancet, this first jab gives me 65% protection against infection, though far more against severe disease and hospitalisation. Excellent! That France and Italy continue to struggle may suggest this single dose ASAP policy is a good one to adopt.

While the debate around this is flavoured and in many ways poisoned by Brexit, clearly in the scramble to do as many early vaccine deals as possible, the UK has led the way, securing far more doses than we need, being miserly with exports of vaccines while at the same time importing as many as we can. This is a model for short term political success and long term pandemic failure, unless of course, we truly remain an island and forbid travel to and from our neighbours.

The pain of slower declines in COVID19 deaths in our immediate neighbours is shown below.

In a further metaphor for all things Brexit, UK politicians keen to hold on to jingoism after being bottom of the pile in all the numbers that really matter for so long, can point to EU confusion and inefficiency and UK supremacy. On the other hand, the Europeans feel rather miffed that the upsurge is being driven by the more transmissible B117 variant, first noticed in Kent and our lack of co-operation with vaccines. This really matters – deaths are actually increasing further afield in Europe, a stones throw away in terms of virology.

The international situation really does mean that undeniable British optimism should at least be a little guarded.

Meanwhile, I hope that our European neighbours get on with their vaccination programme and get as many single doses into as many people as possible. Might we learn from them and offer one booster vaccination to those who already have high antibody levels from ‘natural’ infection?

What if you’ve already had proven COVID19 infection?

It seems that people who have proven COVID19 infections in the past might be adequately protected with one dose only. A small study of health care workers showed an adequate response to a single dose of vaccine in those with proven previous infections. Another pre-print shows that immunity to COVID19 after the infection plus one jab is as good as it is after two vaccinations in people who didn’t have COVID19. They also point out that ‘reactivity,’ that is side effects, are more significant in those with previous proven infections, concluding:

“Changing the policy to give these individuals only (who have had proven COVID19 infection) one dose of vaccine would not negatively impact on their antibody levels, spare them from unnecessary pain and free up many urgently needed vaccine doses“

What about those who are immunocompromised?

The advice from the JCVI seems pretty much the same for everyone, but there are a significant number of people out there who are having treatment for various diseases which compromise the ability of our immune system to respond after an infection – or vaccination. This includes those on chemotherapy, with blood cancers and some people with MS. The Barts team highlight that only about 20% of people on certain MS treatments generate antibodies after the first jab and this was not improved by waiting for 5 weeks for the booster as opposed to the recommended three.

That they are special cases means that they should stick to the manufacturers dosage regime and ideally have the most effective ones available – that is likely to be the mRNA vaccines, though anything is better than nothing. It might also hint that the delayed booster makes more sense for the vector based vaccines like my Astra Zeneca jab and not the mRNA vaccines. The devil is in the detail!

Time for a change of policy?

In France and Italy, this has now become vaccine policy. It seems to make sense in a world struggling to vaccinate, however chaotically, as many people as possible against COVID19, but things are never black and white.

So far in the UK there have been 450,000 patients admitted to hospital with COVID19 and 4.25million people with positive tests. If you have had moderate or severe COVID19 then you might know where you are with this, but for many with lesser infections, is immunity as impressive? Many milder ‘cases’ will have been detected by PCR tests which are very good at detecting viral RNA in small quantities and so will pick up lots of asymptomatic and very mild infections as well as a small number of false positives. And of course there will be lots of people out there who have been infected without knowing it at all.

Thankfully there is evidence of immunity after mild infection. Effective levels of antibodies and T cells were present in 89% of health care workers with mild or asymptomatic infections in a London hospital. T cell (killing the virus directly) responses were greater in those with the more serious infections, but antibodies which neutralise the virus were present in most people. So thats encouraging.

I have not had any hint of a COVID19 infection, so I will wait for my booster which seems to make more sense for Astra Zeneca than Pfizer but seems to have been a sensible policy and a success based on encouraging results from Scotland and England. The latter concluding:

“Combined with the effect against symptomatic disease, this indicates that a single dose of either vaccine is approximately 80% effective at preventing hospitalisation and a single dose of BNT162b2 (Pfizer) is 85% effective at preventing death with COVID-19.”

I must say that if I had already been infected with COVID19, I would have the first dose, probably a few months after the infection, and leave it at that. Those with cancers, on chemo or disease modifying treatments need to seek advice specific to their needs.

In the Real world

Not only is there a priority to vaccinate more people, but there is a priority to vaccinate vulnerable people throughout the world. Speaking from a biological point of view we should be rushing available vaccines, once vulnerable and heath care sectors have been protected, to hot spots around the world, for instance, the Czech republic in Europe and Brazil right now, and anywhere else where viral populations are expanding and mutating and where vaccination coverage is low.

Sadly, it seems hope for this to happen might have been rather Utopian. That us rich nations (primarily the USA and UK) are once again, behaving in a selfish way and vaccinating healthy groups of people before sending vaccines to the places which need them most.