Categories
Covid-19

Answering your questions about the vaccines!

My recent posts have focused on emerging data from the newly licensed vaccines.  As these are now being rolled out, I am aware of many questions that people want answering about the vaccines both for themselves and their families.  In this post I aim to address as many of these questions as I can from the data and expert opinions I have reviewed

Below is the list of questions covered – if you are interested in just specific questions click on the hypertext links

  1. What does it mean that “a vaccine is 90% effective”?
  2. Will I get the same benefit as those in clinical trials?
  3. Which of the available vaccines is the best?
  4. How likely is it will be a one-dose vaccine?
  5. Will having two doses from different vaccines be better than from the same vaccine?
  6. I have had Covid-19 infection naturally, do I need to be vaccinated?
  7. Are the vaccines as effective in all older age groups?
  8. Are the vaccines safe for women who are pregnant?
  9. Are the vaccines safe for the foetus in women who are pregnant?
  10. Are Covid-19 vaccines safe for the infants when given to mothers who are breastfeeding?
  11. Can or should children be vaccinated? 
  12. What about people who have underlying diseases, or are on drugs, that affect the immune system?

What does it mean that “a vaccine is 90% effective”?

  • The figure about the percent reduction comes from the clinical trials
  • The reduction is calculated by comparing the rates of infection  between people who had the new vaccine and those who had the dummy vaccine
  • Thus, if the number of volunteers in each of those two groups in the trial were the same, the number in the real vaccine group who became infected would be one tenth of those in the dummy vaccine group
  • If infection rates are very high as they are at the moment, the absolute number of vaccinated people who get infected will be higher than when infection rates are lower, but the relative reduction should be the same 

Will I get the same benefit as those in the clinical trials?

  • The short answer is we don’t know yet until more data has been gathered. 
  • Obviously the results of the trials are the best estimate we currently have but the vaccines could possibly be less effective in the ‘real world’.  
  • This may be because the people who volunteered for the trials may have been, for example, healthier and  less likely to become infected for a variety of reasons 
  • Experience from the results of many new drugs in general use is that, once they are licensed, their effectiveness is lower than they were in the trials
  • But this may not apply to the current vaccines and the very high success rates reported  in the trials is, I anticipate, likely then to be repeated following their widespread use
  • Of course, the above assumes that no new mutation, like the new UK variant, will be less likely to respond to the current vaccines.  At the moment there is no evidence to support that theoretical worry

Which of the available vaccines is the best?

  • The headline effectiveness rates were higher from the Pfizer and Moderna (RNA) vaccines than from the  AstraZeneca (viral vector) vaccine: does that prove the former two are better?
  • It is not sound statistical practice to compare the results between vaccines that were not directly compared in the same study  
  • There are several reasons for this caution – related to who participated in the different trials; for example the volunteers came from different countries and regions, may have:
    • had different background immunity
    • been exposed to different  mutations of the virus that were around in each trial  
  • The only sure way to compare between two vaccines is to do a ‘head to head’ trial.  Such studies will not be done because they are expensive and not deemed necessary
  • Further, regulators and  governments would argue that all these vaccines are sufficiently successful and we need as many doses of them available as we can get
  • I think though that given the very high success rate for both the RNA vaccines, it is unlikely that any new vaccine could have an even greater success rate – but it is not impossible that say the Astra Zeneca vaccine could have very similar success rates when tested in identical populations

How likely is it there will be a one-dose vaccine?

  • Firstly, for very sound biological reasons the body’s ability to develop a strong immune response to a vaccine is increased with more than one dose 
    • As I wrote  in previous posts on this blog, this is not true for all anti-viral vaccines  but is for most  
    • But all 3 of the recently licensed vaccines were only tested in clinical trials of a two-dose regime
  • Janssen have a vaccine, being marketed by Johnson and Johnson, which showed a strong immune response in the laboratory after one dose – but so did the other vaccines.
    • The Janssen trial in humans, unlike the trials of the other vaccines, is also comparing one versus two doses and we await the results of that study
    • This vaccine is very similar to the AstraZeneca vaccine so (sticking my neck out!) I would be surprised if one dose was sufficiently effective.  The results are due at the end of January

Will having two doses from different vaccines be better than from the same vaccine?

  • Hypothetically this does make sense
  • If the body responds to the virus by producing antibodies that attack it in 2 different ways then this might be a very effective strategy.  (Not an identical parallel but there are many infections that are best treated with combinations of different antibiotics)
  • Indeed this week there was an announcement of a tie-up between AstraZeneca and the Russian Sputnik vaccine, which is an interesting idea
  • There are particular reasons for trying this combination.  Both these vaccines have DNA instructions to make just the spike protein bit of the Covid-19 virus
  • This DNA piece is then bolted on to another harmless virus (called a viral ‘vector’-literally carrier).  This carrier virus is a human virus in the Sputnik and a monkey one in the AstraZeneca vaccines  
  • Thus as the body might make antibodies to the vector in the first dose, as well as to the spike protein, then a second dose with the same vector might be ‘neutralised’ by these unwanted antibodies
  • Having a different vectors for each of the two doses makes that much less likely

I have had Covid-19 infection naturally, do I need to be vaccinated?

  • Short answer is ‘Yes’, for many reasons!
  • Firstly, we don’t know how long immunity from natural infection will last so you may not still be immune
  • Secondly, some people with mild infection or who have had no symptoms may have little natural immunity to start with
  • Finally there is no specific extra risk from a vaccine if you have some immunity, think of it as an extra booster!

Are the vaccines as effective in all older age groups?

  • Success may not be as good as we get older, as in general the body’s ability to produce antibodies does decline with age
  • In the trials, despite recruiting very large numbers of volunteers, there were too few people aged over 65 who became infected to provide a definitive answer
    • AstraZeneca provided no data on age group in their trial
    • The Pfizer trial did show an identical success in those above and below the age of 55 and the data supported a similar reduction in risk in those over 65, but there were too few over 75 for any useful conclusion
    • In the Moderna trial the effectiveness was lower in those over 65 (86%) than those under that age – but 86% is still very satisfactory
  • My view is that even these limited data are much more encouraging relative to what I might have expected – the effectiveness will not be as high I am sure in those over age 65 but might be ‘high enough’.  We will get more data in planned future analyses from all these vaccines 

Are the vaccines safe for women who are pregnant?

  • Again, short answer is we don’t know as women who were pregnant or were considering pregnancy were excluded from the clinical trials
  • Almost certainly as the vaccines are being rolled out in different countries especially amongst key workers in the health and care sectors, many of those will be pregnant at the time they are vaccinated, so some data on risks and benefits will emerge
  • However, pregnancy is associated with a decline in natural immunity (so the mother doesn’t ‘reject’ the baby)
  • A report from the USA identified 8000 pregnant women who were also infected with Covid-19. These women had a fivefold risk of being admitted to hospital and a twofold risk of needing ventilation compared to similar aged non-pregnant women
  • So, for some groups who have high risks of exposure (eg nurses) vaccination is now advised
  • Despite the absence of data from the use of vaccines, all experts are of the view that that the RNA vaccines (Pfizer and Moderna) – which do not contain live virus – should not be any risk to the mother  
  • The AstraZeneca vaccine contains a live but harmless virus so again experts believe it should pose no harm

Are the vaccines safe for the foetus in women who are pregnant?

  • Expectant parents do worry about taking anything that might damage their growing foetus
  • There are limited data but most reviews I have read confirm that there could well be a small chance of serious defect in the foetus for a mother who contracts Covid-19 infection early on in pregnancy 
  • Despite presumably the large number of such women worldwide who had Covid-19 in pregnancy, there only a very few reports of serious defects.
  • There maybe a small increased risk but how large this is is not known
  • Further even if the virus itself did not cause the defect, some of the treatments that might be needed if the mother was really ill with Covid-19 could also be harmful
  • We have no data yet on the risks from vaccines to the foetus and newborn infant
  • Most experts therefore believe that any risk from vaccines to the foetus is probably outweighed by the risks from the mother being infected

Are Covid-19 vaccines safe for the infants when given to mothers who are breastfeeding?

  • Again, there are no data on this 
  • Given what we know about what is in the vaccines and how compounds are transmitted through breast milk,  there is no reason to believe that any of the vaccines licensed for use pose a risk to the mother who is breastfeeding
  • Indeed, there is evidence that some of the antibody protection that the mother has from vaccination may be passed into the milk and may give some protection to the feeding infant
  • Generally speaking though, we shouldn’t rely on maternal immunisations to protect infants from any infectious disease 

Can or should children be vaccinated? 

  • As is well known, children are at very low risk of a serious complication from Covid-19*.  Indeed,  if Covid-19 only affected  children then probably no one would have considered developing a vaccine
  • Children are however at no different risk of contracting the infection and passing on the virus to others
  • Indeed because of their greater social interaction, and the high proportion without symptoms, child-to-adult transmission is an important route for adult infection
  • The situation in terms of vaccinating children is complicated!
    • In the UK the Pfizer vaccine is only licensed for those over the age of 16 and the AstraZeneca over the age of 18
    • In the USA the Pfizer and Moderna vaccines are licensed for children over the age of 16
  • All companies have some data from their trials on younger children but not sufficient for regulators to make a decision about their use
  • Childhood response to vaccines does vary and will thus need specific studies to address the level of antibody and other immune response
  • For the moment no vaccines will be delivered to children  

*Readers will remember possibly media reports of very rare complications of Covid-19 in early childhood now called “Multisystem Inflammatory Syndrome in Children (MIS-C)”. This is so rare that further discussion is outside the focus of this post

What about people who have underlying diseases, or are on drugs, that affect the immune system?

  • Doctors use the term ‘immunosuppressed’ to cover this very large group of people in the population 
  • This has been the largest source of questions from readers who have contacted me and I understand their concerns
  • Becoming infected with Covid-19 in people who are immunosuppressed poses much more of a risk and hence up to now they have been advised to shield as being particularly vulnerable
  • Thus the availability of a successful vaccine for this group could allow a return to a much more normal life
  • There are though 2 separate questions in this situation:
  • Are vaccines safe?
    • For vaccines that do not contain a live virus eg Pfizer and Moderna, most experts do not see why there should be any risk for those who are immunosuppressed and hence should be safe
    • For vaccines that do contain a live virus, even a harmless one such as in the AstraZeneca vaccine, expert opinion is more divided.  The problem being as with so many other issues, immunosuppressed people were excluded from the trials
    • Data from use of vaccines for other infections are also challenging to interpret but, for many of these diseases, live but otherwise harmless viral vaccines are not advised
  • Are vaccines effective?
    • This is also more challenging as immunosuppressed people may be less likely to produce a good enough immune response to give protection 
    • Again, there are no data.  But, as Fauci says, where there is no concern about risk, having the vaccine even if it may not be as effective as in a person with normal immunity is not a reason not to be vaccinated
  • I would make two other points if the above sounds disheartening
    • Immunosuppressed individuals will benefit from herd immunity so they may not need to be protected themselves (but this is another reason why those who don’t have such problems agree to be vaccinated!)
    • There will be other options including new vaccines that are antibody based such as the ‘second’ new AstraZeneca vaccine 

Note to all the readers – I welcome comments especially on items that are unclear or are not addressed. I regret I am not able to answer individual emails. This blogpost is not a substitute for obtaining individual clinical advice

If you would like to receive email notifications of new posts on this blog just click this link and enter your email at the bottom of the home page: https://makingsenseofcovid19withs.com

2 replies on “Answering your questions about the vaccines!”

Thank you for great blog.
Unlike Edward Jenner’s ability to test his vaccine by injecting smallpox infected puss into his trial subject treated with vaccine from milkmaid infected with cowpox, the Covid vaccines are unable on ethical grounds to challenge with virus exposure during clinical trials leaving ambiguity as to extent of virus exposure between treated and placebo (was this even tracked and reported?).
Now we’re into “Phase IV trials” with the public at large, is ongoing performance being made available for Covid rates contrasting between vaccinated and unvaccinated population?

Like

Thanks Danny. Great points!
There is a study that has or is about to start in the UK. I have to say that I am anxious both ethically about this and how much it would change strategy. I did discuss this a few months ago (https://makingsenseofcovid19withs.com/2020/10/01/is-there-a-short-cut-to-prove-a-vaccine-is-successful/ ).

The Phase 4 studies I assume should be done, indeed regulators would have mandated these I am sure. But I don’t think that data are being gathered routinely. The Phase 4 anyway will focus on safety (short and long term). There are probably too may differences between vaccinated and unvaccinated populations to interpret differences in rates of infection. There is also the challenge that ascertaining new cases is challenging – is it self diagnosis, regular swab testing, etc etc. The easiest will be linkage studies to medical records

Like

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s