Long CoVid: is it different from the long term effects after flu?

8 March 2021

As the concerns about the life-threatening risks from CoVid-19 are beginning to recede, so there is growing interest in the long-term effects following infection.  Whereas it might be expected that those who had suffered severe complications and been hospitalised would have continuing health issues, the concern now is that those with mild, or even asymptomatic, infection would have continuing symptoms over several months.  In this post I consider the evidence. 

Before Covid-19……

This banner headline from Medical News Today was from an article written in October 2019  just before the pandemic (how coincidental was that!)

  • It acts as a reminder that following the recovery from the acute stage after any viral infection, a proportion of patients continue with symptoms, most specifically:
    • Fatigue
    • Lack of energy
    • ‘Brain fog’ 
  • Post-viral fatigue/syndrome was a helpful term in describing this experience
  • The relationship with a prior viral infection is not clear, as many suffer the same symptoms without evidence of a proven prior virus  – leading to the non-specific term chronic fatigue syndrome (CFS) *
  • The proportion of people who have continuing symptoms, following flu for example,  does vary between reports – depending on how the cases were recruited – but there is no debate that the continuing fatigue can occur in some people and last for a long time
  • A more potent viral infection causing long-term fatigue is glandular fever (infectious mononucleosis).  This infection has a predilection for young people and many students have had their university courses seriously affected by the long-term effects following this 

*I do not wish to get into the debate about the name ME – myalgic encephalomyelitis – just to say that I do not find it helpful as whilst the ‘myalgic’ bit, meaning muscle ache, may be descriptive, the ‘encephalomyelitis’ term is misleading – and should be reserved for the specific and severe acute brain infection, which is exceptionally rare in individuals with CFS 

Theories about the cause of post viral fatigue

  • There are many theories and this post is not the place to discuss the hundreds of studies that have proposed or disproved various biological explanations
  • Of relevance to Long CoVid is the observation in some studies that it is the body’s own immune system that goes into overdrive in some people, that explains the continuation of symptoms

What is Long CoVid?

  • It is one thing to say that some people have continuing symptoms, it is another to have a definition that can be used as a label
  • That’s important as it is impossible for example to compare between studies, or to consider who should have specific treatments, unless there is a common rule for saying ‘this is a case of Long CoVid’
  • The problem is there is no simple agreed definition:
    • The UK’s: National Institute for Health and Clinical Excellence – NICE- came up with this scheme which separates out short-term and longer-term problems
    • How useful they are is debated and not agreed internationally
  • At the moment therefore, rather than use Long CoVid as a term describing a specific focused disorder, it is used as an umbrella term to cover all the people with continuing problems
  • Thus, the focus has been on attempting to identify how often this happens, what are the symptoms and who is at risk 

How often do symptoms persist?

  • As mentioned at the beginning of this post, the key question for me is not about the continuation of symptoms in people who have been in hospital, but what happens to people in the community who have been tested positive
  • I am going to give the results of the UK’s population survey (Office of National Statistics – ONS study) which followed up 9063 people between April and December last year, who had tested positive in their ongoing population surveys to find out if they were unwell at 5 and then 12 weeks after the positive test.
  • They asked about 5 symptoms:
    • Fatigue
    • Cough
    • Headache
    • Loss of taste and smell
    • Muscle aches
  • This what they found in terms of one or more of these  symptoms:
  • A word of caution of course: these are common symptoms, even without the virus. Thus the people in the ONS survey who tested negative for CoVid-19 may have had the same symptoms but they were not followed up.
  • The ZOE-Kings College App, used by millions in the UK and USA, has been tracking symptoms in people with and without CoVid-19 to provide a suitable comparison 
    • People were asked about symptoms 28 days after a positive test
    • A comparison group (same age, gender etc)  who never tested positive were asked about symptoms at a random time 
    • The CoVid positive group had 6 times the rate of these symptoms

Which specific symptoms persist?

  • The ONS survey showed that most people who reported symptoms had 2 or 3 of the 5 symptoms above, with no single symptom being the more common

What are the risk factors?

  • Role of gender
    • What is a little interesting from the data above is that the rates of reporting were slightly higher in women then in men 
    • Remember it is men who are more likely to be hospitalised from the CoVid
  • Role of age
    • Older people were more likely to report continuing symptoms
    • Unlike the risk of life-threatening complications, the proportion with symptoms did not change that much across the adult age span
  • Also note that children who test positive are not free of long term symptoms Indeed, children commonly report other long-term symptoms including:
    • Sore throats
    • Mood changes (I assume more than normal!)
    • Rashes
  • There are other groups of people who are more at risk of Long CoVid.  These include those who:
    • Are obese
    • Have pre-existing conditions such as asthma
    • Have specific Covid-19 symptoms such as loss of sense of taste and smell

Does it all sound rather minor?

  • At first glance the persistence of these symptoms may be considered, because they are not life threatening, as not too worrisome
  • That of course underplays the impact on individuals of the persistence of feeling unwell
  • There is another side to the Long CoVid story, which is the risk of new serious health problems
  • Although it is difficult to put numbers on what are quite small risks, there are a number of serious late effects with CoVid-19
  • Many of the more serious consequences are thought to be due to blood clots and scarring of major organs including:
    • Lungs
    • Heart
    • Kidneys
    • Liver
    • Gut
    • Brain
  • Plus some patients have reported the development of other diseases associated with the body’s immune system attacking itself
  • Perhaps less expected is the possibility that CoVid-19 could lead to the development of diabetes
  • Although many CoVid-19 patients with new diabetes are those who had been hospitalised with severe infection, this is not always the case
  • I am going to be cautious again though in giving conclusions about these serious consequences – why?
    • The numbers for each of these complications are very small
    • Given the millions affected by CoVid-19, some of these severe problems might have arisen by chance, independent of the CoVid-19 
  • But they should not, and are not, being ignored and more research is ongoing

Why CoVid-19 might be different from other viruses in its long-term complications?

  • Having read thus far, you might feel that I have not made a case that there is an undoubted issue with Long CoVid that is different from the problems people report following flu
  • The numbers of those with continuing disabling symptoms are higher – although the quality of data from other common viruses is poor
  • I am however persuaded that this virus is different because of some special features that I have mentioned in previous blogposts
    • The virus locks onto a protein found on the surfaces of cells of many of our organs called the ACE receptor and this can explain why organs such as the lungs, kidneys and heart could be damaged
    • As part of the body’s response to this virus, the immune system does sometimes go into overdrive – indeed this unwanted response is the cause of many of the deaths of patients in intensive care units
    • This overdrive caused by the body producing too many nasty proteins called cytokines can damage the walls of our small blood vessels, which makes them more likely to allow clots to form

My take home message

  • We need to think about the long-term consequences of CoVid-19 seriously
  • There can be long-term symptoms even in those who had mild infections or even were asymptomatic
  • The overwhelming majority do recover but a significant minority have continuing health challenges to their everyday life for some months
  • This includes people of all ages including children
  • It is difficult to put numbers on the level of these risks and serious long-term effects will still be the exception 
  • The diabetes story is intriguing
  • And my answer to my opening question: I think this is different from the issues seen in recovery from other viruses, especially flu 

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Predicting when the pandemic will end: the role of super-spreaders?

The rolling out of national vaccination programmes on their own will not completely eradicate the virus, because even the most successful vaccines cannot prevent some transmission.  Interest is now focusing on the possible role of ‘super-spreaders’ in maintaining the pandemic.  In this post I review some very recent data on what makes a super-spreader and what influence they might have on the future number of cases.

Apologies but I do have to mention R!

  • As a concept R (more correctly referred to as R0) – the transmissibility of a viral infection – is helpful:  the greater it is, the more quickly an infection will spread 
  • R is the average number of new cases infected from one existing case
  • Here are the R  values for some common infections that, like Covid-19, are transmitted from person to person in the same ways:
  • No surprises perhaps, although interestingly seasonal flu might have an R below 1, which is why even without social distancing a flu epidemic can die out 
  • Note that these are the values in “normal times”, when there are no preventive measures in place (masks/distancing etc), but of course there will be a range of values depending on how much social contact there is between cases
  • The common-sense conclusion is that these R values are helpful in comparing between viruses, but the precise values are wobbly at best

R  and Coronavirus infections

  • In this pandemic there has been a considerable focus on how transmissible the infection is, for good reasons
  • One major reason is that unlike the infections above, there was no prior disease-acquired or vaccine-induced immunity, so the infection could spread at its ‘natural’ rate
  • So what is our estimate of the ‘natural’ value of R?  In this table I have compiled experts’ best estimates and have compared these with estimates for the other major SARS pandemics and also for the most recent variants 
  • Thus Covid-19 is very similar to the other coronaviruses
  • It is interesting, though, to see how small changes in R can have a major influence on the rate of cases
  • In the figure below, as an example, I used the estimate that in the UK, by the time we got round to doing anything serious about controlling the spread, there were 30,000 cases dotted around the country
  • (for non-UK readers the principles are identical!)
  • I have made a series of assumptions about the period of infectivity, but I have calculated the speed of growth/decline for various values of Rfrom a high of 2.5 to a low of 0.7, over a 12 month period
  • The red dotted line is for R of 1, so the number of cases (in this example 30,000) stays the same over the year
For those of you not familiar, the vertical axis is on a logarithmic scale to show the exponential growth 
  • The graph clearly shows that with an R value of 2.5, after 6 months the original 30,000 cases would grow to around 10 million
  • Similarly, with an R value of 0.9, even after 12 months there would still be around 8000 cases: enough to cause problems
  • Getting R to 0.7 though could eliminate the infection (from my calculations!) in 7 months
  • If the R value was indeed  as high as 3.6, or we needed to allow for greater transmissibility of the new variants, then the growth would be even greater

How do super-spreaders change the picture?

  • An R value is an average and would conceal the fact that some people spread to no-one and others to several 
  • There have been some infamous cases, most notably a Santa Claus visit to an old people’s home in Belgium delivered more than they were expecting!
  • This is not an isolated incident but one that, given the circumstances, was easy to track down
  • How much do super-spreaders contribute to the overall number of cases in a population?
  • There has been an interesting analysis from China, which charted the paths by which individual cases in 8 areas caught the infection
  • This is best illustrated in the figure below:
    • In very simple terms, the dots with no lines show cases with no spread, whereas there are some cases who pass on to several others (eg shown by the red arrow)
    • The bar graph shows what proportion of cases passed the infection on to one or more others
    • 80% of cases spread to nobody else
    • Thus just 20% of cases are responsible for the spread of the virus 
    • This highlights the need to consider the role of super-spreaders 

What makes a super-spreader?

  • One question is whether it is there are differences in the virus in people who are super-spreaders
  • The short answer is – very unlikely
  • For sure some new variants show greater powers of transmissibility (see Table above) but:
    • There are super-spreaders with none of the variants
    • The increase in R is modest (less than 1.0)
    • The thought is that people infected with these variants transmit more virus because the mutations allow the virus to replicate more easily and thus infected people breathe out more virus
  • Thus, the answer to ‘why super-spreaders’ must lie within the person.  What are the options?
  • Super-spreaders have more social contacts
    • This is unlikely and did not explain the super-spreading events which had been traced to specific individuals 
  • Super-spreaders generally breathe out more stuff
    • Unlikely as it sounds, this actually may be true
    • We know from experiments that different activities such as singing, shouting etc are associated with breathing out more virus in those who are infected
    • What appears to be the case is that there are some individuals who normally (ie when not infected) breathe out more droplets (which in an infected person could contain the virus)
    • Look at this data from a non-per-reviewed publication of 2 weeks ago
    • In this study 74 volunteers had their breath examined for the number of droplets they breathed out
Each line represents one person: so the biggest exhaler breathed out over 3000 droplets, with many others breathing out less than 10 that barely register on this graph
  • This shows dramatically that there are 1000-fold differences between normal people in the amount of droplets that they breathe out
  • Is there anything different about people who breathe out more droplets?
    • The same study showed that older people breathe out much more than younger people
    • (This might explain the lower transmissibility in children)
    • People who are more obese breathe out more droplets than leaner folk
    • Adding age and obesity together, as these researchers in the USA did, showed that indeed super-spreaders 
      • did breathe out more droplets and
      • were much more likely to be older and fatter
    • This is illustrated in the graph below 


  • Even with the current reduction in transmissibility (as a consequence of the lockdowns in different countries), the infection will still take several months to essentially stop being a public health problem 
  • Super-spreaders could make an important dent in the success rate
  • These preliminary results suggest that it would be helpful for efforts encouraging mask-wearing to focus on those most at risk of exhaling large amounts of droplets
  • It would be a shame to constrain the obvious success of the vaccines in substantially reducing the severity of Covid-19 by not considering this issue

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Pfizer vs AstraZeneca vaccine: first comparative data

For update May 7th on the effectiveness of the Pfizer vaccine in controlling the pandemic visit the post

The number one question that people in the UK when chatting to each other in the past few weeks is “Which vaccine did you have?”!

Yesterday (22nd February) the Scottish Government published preliminary data from their first 1.1 million people who had been enrolled in the national vaccine roll out programme.  This programme, like the rest of the UK, involved using both the Pfizer and AstraZeneca vaccines.  These data are the first real world information on whether there are any differences between the success rates from these 2 vaccines. 

What did we know before this Scottish Study

  • Both vaccines target the spike protein of the virus
  • They do this in slightly different ways*:
    • Pfizer by providing the genetic instructions – mRNA – to make the spike protein 
    • AstraZeneca by providing an earlier stage of the same genetic instructions which are bolted onto to a harmless virus to then make the spike protein
  • By targeting the same spike protein, indeed the same genetic version of the spike protein, in theory both vaccines should be equally successful
  • The key clinical trials before the vaccines were licensed however showed that
    • Pfizer gave 95% protection against being ill with 2 doses 3 weeks apart
    • AstraZeneca gave a lower protection but this could reach 85% with 2 doses 3 months apart

*See post:

Other challenging news for AstraZeneca 

  • These headline differences in the results between these trials seemed to suggest that Pfizer might be superior 
  • It is not possible to compare the results of two trials done in different populations at different times – why not?
    • Because the overall background infection risk may have been different in the volunteers in the trials
    • The way that the 2 studies were designed meant that they had different ways of identifying the cases of Covid-19 that emerged during the follow up
  • Nonetheless further support for Pfizer’s success came from the results from Moderna vaccine – an almost identical vaccine to the Pfizer – which produced the same very impressive reduction  
  • AstraZeneca also had not included many elderly people (aged over 65) in their trial, and this lack of data – in the population most at risk of serious consequences from the infection – raised concerns that the AstraZeneca vaccine might not be effective in older people
  • On the back of that concern, many European countries in high profile declarations, suggested they would not be using the AstraZeneca vaccine
  • Further, recent data from a study in young South Africans showed the AstraZeneca vaccine did not reduce mild to moderate infection: the trial was abandoned and the South African government threatened to return their supply of the AstraZeneca vaccine
  • This concern was fuelled by the emergence of the new South African variant, which was responsible for the cases in that study
  • The UK is currently the only country routinely using both the Pfizer and AstraZeneca vaccines in any number
  • In all 4 nations of the UK, who receives which vaccine is determined by logistics issues and vaccine availability and patients have no choice 
  • (For interest my wife and I had our first doses just 3 days apart at the same centre, she had Pfizer, I had AstraZeneca!)
  • Thus, the first data on the relative success of these two vaccines is of substantial interest as many people in the UK ask – although they have no choice – ‘which should I have?’

The Scottish Study published yesterday

  • As with all these studies, although this is a publication from the government agency – Public Health Scotland (PHS) – it has not been peer reviewed and we should treat the results as preliminary
  • To be honest, the report I have seen is not well written and I have a number of questions about the data. I accept that their headline results are probably accurate.
  • The question they asked was a simple one:“How much do the vaccines reduce the risk of being admitted to hospital with Covid-19”
  • Unlike the recently published preliminary studies from Israel, this study was based on a stronger epidemiological approach
    • They studied data from the entire Scottish population
    • They linked these 3 national databases
  • It is having access to the whole population that makes this study so powerful
  • This is how they analysed their data
  • Their access to general practice data allowed them to identify individuals who had, and who had not, been vaccinated – the dark green boxes
  • They identified all people who had been in hospital with Covid-19, but only included those cases who had a positive PCR test – the light green boxes
  • They then compared the rates of being admitted between people who had and had not been vaccinated – the red and purple bordered light green boxes
  • The most impressive part of their study was that having access to these data, especially the computerised primary care records, they were able to account for the fact that people who were vaccinated may be different from those who were not vaccinated in these ways:
    • Age
    • Gender
    • The area where they lived in terms of deprivation 
    • Their background health disorders
  • Plus they were able to allow in part for the fact that those who were vaccinated were more likely to be health or care workers and hence more exposed to becoming infected 
  • They then determined the success of the vaccine programme by working out how far fewer were the number of cases who had been vaccinated compared to the non-vaccinated
    • They compared the numbers in the red bordered boxes with those in the purple bordered boxes
    • Thus, if there were only half the risk of PCR positive hospitalised cases in the vaccinated group to that in the unvaccinated group, this was a vaccine efficacy of 50%
  • In doing these calculations they took into account the other differences between the 2 vaccine groups listed above (eg age etc)
  • As the research assumed vaccine efficacy would increase with the more days after the first dose, they compared the efficacy of the vaccines at the different time periods
  • All the data refer to the success of the vaccine in terms of days after the first dose
  • This is what they found
  • Compared to those who had not been vaccinated,  there was a reduction of around 40% in those who had Pfizer and 70% in those who had had AstraZeneca in the second week (7-13 days) after the first dose
  • By 5 weeks (28-34 days) both vaccines were increasingly effective at reducing the number of cases – by over 85% in those who had the Pfizer and 94% in those who had the AstraZeneca 


  • As mentioned above, these are preliminary data and have not been peer reviewed
  • Both vaccines, as everyone knows, are designed to be given as 2 doses, but that will only increase their success
  • The data refer to hospitalised cases only and may not reflect how the vaccines work at preventing mild or asymptomatic infection

But on the positive side:

  • Two thirds of those vaccinated were over 65 and almost 20% over 80, so answering the question about success in the elderly
  • Most cases were of the new ‘English’ variant* whereas the trial data were collected before this variant was widespread
  • Who got which vaccine was likely to be random, as this was determined by the logistics of the vaccination programme
  • They could take into account the background differences in risk of severe Covid-19 between those in Scotland who had or had not been vaccinated by the time of this analysis

*There are too few cases so far of the other variants for any of the vaccines to provide robust data


At this stage there is strong reassurance that the two vaccines are both very effective at preventing serious infection after one dose and no suggestion that the AstraZeneca vaccine is any less effective

New post April 28th: Pfizer might be the only vaccine available for children: for the discussion on this see:

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New Israeli data show good protection after one dose of Pfizer vaccine

New data published yesterday in the Lancet appeared to show that there is very good protection from becoming infected with Covid-19 two weeks after one dose of the Pfizer vaccine.  In this post I describe the results, what are their limitations and what they mean.  I also relate the results to similar data from AstraZeneca. 

What did we know about protection after one dose of the Pfizer vaccine before this study?

  • The planned Pfizer vaccine dosage required two doses 21 days apart (although in practice this may extend to 28 days) and the main published clinical trial only reported on the number of cases in the trial occurring from two weeks after the second dose
  • The UK government, as a matter of policy, delayed the second dose for those given the Pfizer vaccine to 3 months – which raised the question as to the protection people would have during that interval between doses
  • Pfizer provided the UK with previously unpublished data from their trial
    • Pfizer looked at how many cases had occurred from 15 days after the first dose but before the second dose 
    • They showed that the numbers of cases in that narrow window of the interval 15-28 days between doses was very different in the vaccine and placebo groups.
  • I had not seen these data before today but they will have provided reassurance to the UK that delaying the second dose will still provide some protection
  • I will repeat this again in this post but 
    • We do not know if this apparent protection after one dose will be sustained beyond 28 days
    • The agreed vaccine schedule for this vaccine requires 2 doses

The new Israeli data

  • It is widely recognised that Israel has led the world in the proportion of the population it has vaccinated 
  • The Pfizer vaccine has been used throughout 
  • A priority target was health care workers, in whom the vaccine programme started on December 19th 2020
  • The design of this study was epidemiologically a clever one and shown in the diagram below
  • They studied all the 9109 eligible health workers in this target group
    • By 24th January 2021 some had had 2 doses, some 1 dose, and others were still waiting for their first dose
    • All workers though provided daily reports on their health to find out if they had developed Covid-19
    • It was assumed that it might take 14 days for the first vaccine dose to have any effect so the research was interested in how many cases occurred in the 3 time intervals from the 19th December 
      • Before they had their first jab (the pink bar)
      • From after their first jab until 14 days later (the yellow bar)
      • From 15 days after until their second jab (the green bar)
    • Most of the infections they captured were from the workers’ reports of symptoms, some were picked up by active contact tracing and were asymptomatic
    • This is what they found:
  • The rate of all cases  – blue bars – (both symptomatic and asymptomatic) fell from the pre-vaccination period by 30% in the 1-14 day period after the first dose and by 75% in the 15-28 day period after the first dose but before the second dose
  • The rate of just cases with symptoms – orange bars – fell from the pre-vaccination period by 47% in the 1-14 day period after the first dose and by 85% in the 15-28 day period after the first dose but before the second dose


  • This is good news, but as with the original trial we do not know if these reductions will be sustained 
  • Even during this period of observation, there may have been differences in how the participants behaved in terms of social distancing (but they were health workers) so perhaps had no choice)
  • Different strains may have been predominant at different periods (but note  also from the design of the study that, for example, some workers only in the pre-vaccine stage for the first week(s) of the study period, whereas others were still waiting for their vaccine and would have contributed more days of pre-vaccination)


  • These data do not prove that one dose of the Pfizer vaccine will be enough, and in Israel as in other countries the two-dose regime will continue
  • The data are reassuring that whilst waiting for a second dose, although social distancing etc should be maintained, for occupationally exposed groups like health and care workers there is reasonable protection

And for AstraZeneca vaccine recipients

  • We have more data on the protection after the first dose from AstraZeneca because of their clinical trial 
  • I discussed these data only recently (
  • Interestingly that report showed a reduction in symptomatic cases after the first dose of around 75% and of all cases by 67%: results that I feel are comparable to these new Pfizer data


  • The data now from these two vaccines show a good reduction in both symptomatic and all cases after the first dose.  
    • For AstraZeneca we know that this persists for 3 months
    • For Pfizer, the length of the protection is not yet known but hopefully results from the UK data will give a similar answer when they are become available over the coming weeks
    • This is of relevance for countries like the UK* with a longer interval between doses

*EMA (European Union) allowing up to 6 weeks and probably will be the interval to be adopted in Denmark and the Netherlands

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Why our T cells could take out anxiety about whether the vaccines are effective: new variants or not!

As vaccine rollout grows apace, the media are full of concerns that vaccines may not protect everyone, and may prove much less useful against new variants of the Covid-19 virus.  The EU announced this afternoon support for researching new vaccines. In this post, however, I want to give a fuller introduction to the less well-known aspect of our immunity: our T cells; and why these cells will do the necessary so that even current vaccines should be effective against the new variants.

A quick refresher on antibodies and Covid-19 

  • Antibodies* are produced a few days after we become infected and neutralise the foreign proteins carried on the surface of the Covid-19 virus
  • The most important of these proteins is the spike protein which is how the virus attaches itself to our cells
  • Following naturally acquired Covid-19 infection, we produce antibodies; the worse the infection the more the antibodies, although those with a very severe infection may have their immune system ‘paralysed’
  • After the infection has settled, antibodies wane and may disappear after a few months
  • The current licensed vaccines act in different ways but all work by getting the body to produce large quantities of neutralising antibodies against this spike protein
  • Either from a natural infection or vaccination (or both), the B cells that produce these antibodies have a memory (very useful!) so they can ramp up production of fresh antibodies when faced with a new infection

*And in case I forget to mention this later on, antibodies are produced by cells called B cells

  • We do know
    • Up to now, a second natural infection is very uncommon, which is evidence that  natural immunity does provide future protection
    • The vaccines all produce very high levels of neutralising antibodies and in clinical trials these are sufficient to:
      • Virtually eliminate deaths or very serious complications if we do become infected
      • Substantially reduce the need to be hospitalised if we do become infected
      • Substantially reduce the overall number of people in the population who are infected, although without reducing the number with asymptomatic infections 
  • We do not know for sure
    • How effective antibodies following vaccination are against new variants but:
      • It seems that sufficient neutralising antibodies are produced to stop serious consequences of infection
      • The well-publicised, small, and not peer-reviewed, study from South Africa also suggested the AstraZeneca vaccine may not prevent mild illness in young people
    • How long the antibody response could remain active for, without needing a third dose of vaccine

Let’s look at T cells!

  • I like this picture which shows the  large T cell doing its stuff against the smaller Covid-19 virus (they are the blue cauliflower looking blobs!)

A simple guide to how do T cells work:

  • T cells respond to getting a message that there is a foreign protein (such as from the virus)
  • There are two types of T cells: ‘Helper’ and ‘Killer’
  • Helper cells really are very helpful and can multitask so they can:
    • kickstart the B cells to produce antibodies
      • this could be the first time, triggered by an infection  with Covid-19 or the first dose of a vaccine
      • or could be jogging the memory in the B cells to wake up and start producing fresh antibodies – a bit quicker than first time round
    • send another type of cell into action to eat up any bits of virus they see
    • most importantly they support their ‘brother-in-arms’, the killer cells, to go after any cell that contains the virus and destroy it
  • So Killer cells do just that!
  • They attack cells from the inside and kill them and their viral contents
    • This is unlike antibodies that can only attack from the outside
    • These cells do not change their spots: ‘once a killer always a killer’ but after doing their bit, they also hibernate and the helper cells will wake them up when faced  with a new infection

  • What we know about how T cells work after natural infection and vaccines 
    • There has been a lot of research as to how long after an infection the T cell responses continue to work
      • My reading is that the T cell responses are less likely to wane than the antibody response 
      • Interestingly these T cell responses in some people may be present from contact in the past from other coronaviruses – in particular, from the 2003 SARS epidemic
    • In laboratory testing, all the vaccines produced very strong T cell responses
    • Although we need longer-term data, the T cell responses following vaccination last as long as, and possibly longer than, the antibody response.

Why T cell responses may be more resilient to new variants

  • Firstly, the T cell system responds to many of the different bits of foreign proteins whereas the antibody is response is more focused
  • Why is this important?
    • Scientists estimate that perhaps we will produce separate T cells against may be 15-20 different bits of the spike protein 
    • Given this number of different T cells, they can then fight the virus on all these different fronts – making it much harder for any new variant to completely escape 
    • This is all hypothetical, are there real-life data?
  • Secondly, there was an interesting paper published last week from looking at results of vaccines
  • They studied people who had been vaccinated 
    • They research looked in detail at how their T cells responded
    • They found that the response by T cells to the spike protein generated from the vaccines was much  broader than that resulting from natural infection
    • They concluded from their results, that these T cell responses would still be active against the spike protein seen in the South African or related variants
  • My conclusion: OK I’ll be cautious – laboratory data is not the same as evidence from real live patients; but in theory our T cell responses to vaccines should be good enough to protect against new variants
  • Trying to put this all together my take is as follows:
    • T cells work once the virus seriously invades cells.
    • T cell response following vaccines might therefore not be expected to stop the early stages of infection from new (or indeed old) variants
    • However, T cell response following vaccines could be sufficient to stop the infection being severe from any of the known variants

One final piece of exciting news on the horizon 

  • As mentioned, all the information above relates to the spike protein, this is because
    • all the licensed vaccines are directed against the spike protein
    • this is where the mutations are in the new variants 
  • New vaccines are now being developed (by biotech companies such as Grimstone) to produce T cell responses against a broader range of proteins
  • Thus whatever mutations may appear in the spike protein, such new T cell based vaccines will have loads of other targets to attack the virus with
  • What I liked was the reported comment from Gritstone’s CEO, that they were happy to do this development but hoping that this might not be necessary because our T cell responses to the current vaccines would be enough!

(Acknowledgment: much of the material in this blog is based on the excellent piece in Nature by Heidi Ledford: )

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Short term side effects following Pfizer and AstraZeneca vaccines: data from first 7 million UK jabs

The clinical trials of all currently used vaccines studied relatively small numbers of people. As volunteers they were also healthier and younger than the general population.  Now, after millions of doses of the Pfizer and AstraZeneca vaccines have been given in the UK, we have much more data which apply especially to older people and other groups vulnerable to the consequences of Covid-19.  I think we all need this information both for our own reassurance and to counter concerns of others.

Source of the new data

  • In my previous blog* (posted on my birthday 4th December!) I outlined the different sources of data on side effects from vaccines following their introduction
  • The most rapid source of data is based on individuals and their health care professionals reporting to a centralised database a suspected side effect


  • The main disadvantages of this system are threefold:
    • It is impossible to calculate the actual frequency of any reported medical condition after vaccination.
    • There will be substantial under-reporting but the completeness is likely to be greater though for novel and/or severe problems
    • To make sense of the number of reports of serious disorders, we also need to know how frequently such cases may arise in the general (ie unvaccinated) population. 
    • The fact that even an unusual disorder follows a few days after vaccination does not prove cause and effect 
  • With these cautions, I consider the recent data produced by the UK regulator (MHRA) on possible side effects reported from the first 5.6 million doses of the Pfizer vaccine and 1.5 million doses of AstraZeneca vaccine 
  • In total MHRA received around 23,000 reports of adverse event, equivalent to 3/1000 jabs

Expected side effects

  • We already knew from the clinical trials that there were a number of very common, short-lived, side effects and a high proportion of these 23,000 reports were for these same symptoms
  • From the MHRA reports can be added other common short-lived side effects: 
    • Numbness/pins and needles in the arm and/or hand
    • Rapid heart rate/palpitations
    • Diarrhoea
    • Shaking
  • The occurrence of all these common side effects could be considered ‘good news’!
  • Remember the vaccines involve injecting into muscle a relatively large quantity of foreign material 
    • We want there to be an immediate response from the body’s first line, general immune defence mechanisms
    • These are referred to as our innate immunity, are nothing to do with antibodies and are not specific to any vaccine or indeed any infection
  • If you don’t have any side effects, that doesn’t mean the vaccine hasn’t worked for you
  • The other major reason of course for collecting data about these side effects is that vaccine centres/patient information websites etc can draw on these to provide reassurance to people that their symptoms 
    • Are not unusual
    • Do get better
    • Are a sign that the vaccine is working
  • There are conflicting reports as to whether side effects are more or less likely with a second dose.  This would be useful public information but there is not a definitive answer yet

Anaphylaxis/severe allergic events: the concern This has been the major concern for many people who have had severe allergic reactions to vaccines, other medicines as well as other chemicals

  • The concern has been more about what else is in the vaccine as opposed to the actual active bit
  • None of the vaccines contain egg albumen
  • The Pfizer (and Moderna) vaccines do contain polyethylene glycol (PEG), a chemical which is also widely used in food preparation
  • PEG enhances the immune response to the active component in mRNA vaccines 
  • Allergy to PEG does occur but is rare and people who have experienced this in the past are advised to avoid the Pfizer vaccine.  
  • The AstraZeneca vaccine does not contain PEG but does contain a similar compound, Polysorbate 80, which is probably less allergenic than PEG
  • National authorities only recommend not being vaccinated if there has been an issue with a constituent like PEG
  • Allergies to other chemicals/foods/drugs are not a contra-indication to being vaccinated 

Anaphylaxis and severe allergic events: the data

  • Obviously we don’t know how many people have refused vaccines because of concerns, whether appropriate or not, because of past allergy history
  • There have been only a tiny number of cases of anaphylaxis reported in the UK
  • All these patients recovered

*In the UK because of the issue with PEG, people who are vaccinated with the Pfizer vaccine are asked to wait for 15 minutes before leaving.  The risk from polysorbate is considered much lower

Conclusion: Severe allergy to vaccines is only an exceptionally rare complication

Severe neurological complications

  • There was widespread publicity in September to a case of the rare spinal disease, transverse myelitis, in a participant in the AstraZeneca trial
  • This led to a pausing of the trial in UK and (for a much longer period) in the USA) 
  • The good news  from the MHRA data is the extreme rarity of any serious neurological complication
  • Just one case of transverse myelitis each in the Pfizer and AstraZeneca vaccines
  • And of course those cases may be completely unrelated to the vaccine 
  • The other serious neurological disorder, which was reported in one individual during the early clinical trials, was Guillain-Barré syndrome (GBS): a rare disease which causes progressive muscle weakness because of an immune reaction, possibly to a virus
  • Indeed GBS is a theoretical complication from Covid-19 infection itself
  • The good news again is that only one further case has been reported with the Pfizer vaccine and none from the AstraZeneca vaccine
  • There have also been no other reports of other serious, possibly immune-related neurological disorders such as multiple sclerosis 
  • Conclusion: The worries about severe neurological complications are at this stage unfounded

Any unexpected side effects?

  • The only side effect reported in any significant number is Bell’s palsy (see picture at the top of this post)
    • This disorder is a paralysis of the facial muscles on one side
    • Can be a complication of a viral infection 
    • It does get better and most people are fully recovered by 6 months
    • Is treated with steroids
  •  In the UK dataset  there have been:
    • 69 cases following Pfizer (13/million)
    • 6 cases following AstraZeneca (4/million)
    • But around 200/million people per year in the general population get this condition
  • Conclusion: Despite the publicity the number of these cases is no higher than the general population incidence 

Why I find these data important

  • I have been giving a number of online talks to community groups about Covid-19 in general and, more recently, vaccines in particular.  Two weeks ago I came across my first ‘anti-vaxxer’ who asked:

How could I guarantee the vaccines were 100% safe (especially for a young non-vulnerable person such as myself?)”

  • I think my answer was a bit weak as I emphasised the much greater and known problems from Covid-19 itself
  • If I was asked this now my answer would be:

“I am confident that there is  a much bigger risk of having an accident in the car on the way to vaccination than any serious health risk from the jab itself”!

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Mixing vaccines: taking two doses of different vaccines seriously!

This week has seen research supporting the idea that having the two doses from different vaccines would be more effective than two doses of the same vaccine.  This idea is being taken seriously and thus this week there were announcements of two trials:

  • In the UK with AstraZeneca and Pfizer vaccines as the different doses
  • In Azerbaijan & UAE using AstraZeneca and Sputnik vaccines as the different doses. 

In this post I discuss the background and what may be the potential benefits of such ‘vaccine mixing’.

The case for these 2 combinations are different

1. Pfizer/AstraZeneca

Rationale for a Pfizer/AstraZeneca 2-dose vaccine regime

  • Pfizer and AstraZeneca  vaccines are both designed to produce the spike protein that when injected leads to immunity to the real virus
  • The spike protein produced by these 2 vaccines should be identical as the genetic instructions were based on the same genetic code, they just work in different ways
  • Theoretically then the body’s immune response to either of these vaccines should be similar.
  • Readers may recall that we have two immune responses to vaccines:  
    • Antibodies 
    • T cells*
  • These 2 immunity weapons both need to work to get full protection
  • It was thus interesting that a (not peer reviewed) paper published  a week ago showed that there may be differences between these two types response  between the 2 vaccine:
    • Pfizer is better at antibodies
    • AstraZeneca is better at T cells

*Some readers may have seen the recent TV series “It’s a Sin” about HIV/AIDS.  The pneumonias that caused some of the deaths caused are a consequence of the failure of some T cells (CD8) that protect against infections in people infected by HIV

  • Thus having these 2 different vaccines can have a theoretical advantage
  • A second consideration relates to side effects:
    • Side effects from the second dose of the Pfizer vaccine were reported this week to be worse than after the first dose
    • Switching vaccine to the AstraZeneca could possibly protect against this 
  • There are also logistical  justifications for testing this mixing:
    • Given the complexity of how they are made, production of these vaccines is a precarious process and even with all the quality controls in place, something could go wrong, limiting the availability of the product
    • AstraZeneca vaccine is far cheaper to produce and distribute 
  • So knowing that one of these vaccines can substitute for the other can be very helpful

Rationale for  AstraZeneca/Sputnik two dose regime

First let me introduce you to the Sputnik vaccine!

  • When Russia announced the launch of their ‘Sputnik’ vaccine in August 2020, Western media were concerned that the necessary clinical trials had not been completed prior to its wider use.  
  • Thus it might seem strange that, only a few months later, formal clinical trials are going to start in collaboration with AstraZeneca  
  • Whatever the views about the political situation in Russia, this is an interesting vaccine!
  • Basically, it is the same type of vaccine as the AstraZeneca one: so-called ‘viral vector’ vaccines, and also planned to be given in 2 doses 
    • The  term ‘vector’ means that the active bit of the vaccine – the genetic instructions to make the spike protein – is carried on a harmless virus 
    • The harmless virus in Sputnik is one that affects humans whereas that in AstraZeneca is a monkey virus – though this difference probably doesn’t matter
    • However, whilst the AstraZeneca vaccine uses the same monkey virus in both doses, the two doses of the Sputnik vaccine uses two slightly different human viruses 

Is the Sputnik vaccine successful?

  • Results from the Sputnik vaccine were published in full in the Lancet this week
  • Note that the first reports of the success from the other vaccines have come from a press release or an early version of the results not checked by peer review 
  • The results of this clinical trial of Sputnik with placebo, comparing 2 doses 3 weeks apart with a placebo, were impressive
  • The number of cases in each age groups was too small for very accurate analysis, but there was no indication that Sputnik is less effective in people aged over 60 
  • They didn’t collect any data on asymptomatic cases so we can’t comment on whether Sputnik reduces transmission
  • Conclusion: The results from Sputnik, albeit in very different populations, are at least as impressive as the AstraZeneca vaccine 

Back to the rationale for mixing these vaccines 

  • There is a plausible biological pathway for understanding why a pairing of the two vaccines  may be better than just two doses of the AstraZeneca vaccine 

  • Why this is of interest is a little bit complicated, but is important to understand as it underpins why mixing these 2 vaccines may be useful!
  • Here is a picture of the AstraZeneca vaccine (or indeed the Sputnik vaccine)
  • It shows the two parts: the carrying virus and the bit to make the spike protein
  • When injected as a vaccine, the body produces antibodies against both parts of the vaccine as in the picture on the right
  • The antibodies against the spike protein (blue arrow) are what we need to fight the virus when it attacks
  • The antibodies against the carrying virus (red arrow) probably don’t matter
    • BUT these antibodies could theoretically attack the carrier virus in the second dose of the AstraZeneca vaccine
    • AND reduce its overall effectiveness
  • With the Sputnik vaccine, using a  different carrier at each dose reduces this risk
  • This is a theoretical advantage of the Sputnik over the AstraZeneca vaccine
  • And therefore this is also a theoretical advantage for combining the AstraZeneca and the Sputnik vaccines 

Challenges of doing ‘mixing’ studies

  • It is not that simple to know how best to study the benefits of mixing compared to sticking with one vaccine 
  • Given what we know already about these vaccines, it would be almost impossible to prove that a mixing regimes (mixed) was better than 2 doses of the same vaccine (same)
  • This is because all the individual vaccines:
    • Lead to a very large  reduction in the number of cases.  
    • The numbers that therefore in any trials that would need to be studied to show that ‘mixed’ was better than ‘same’ would be enormous!
  • My guess is that studies are more likely just to analyse the laboratory results of these different regimes, in the hope that if the lab outcomes were the same then the clinical benefits should follow – though this is not necessarily true

What about new variants of the virus?

  • All these vaccines were designed to work against the initial variants which may be an issue
  • However, the AstraZeneca but especially the Pfizer and Moderna vaccines can be very easily modified to work better against the new variants, so for some people their second dose (booster dose) could be in theory ‘a different vaccine’.
  • More importantly, if one vaccine is easier to produce in a new-variant-proof version, then this could well be the vaccine of choice for the second dose, independent of the vaccine in the first dose


  • This is a unique situation in public health; for most viral vaccines we are not faced with this choice or this dilemma
  • Thus far, the vaccines licensed for use all work extremely well in leading to enormous drops in the number of people becoming seriously ill, so there is not an immediate powerful case for mixing 
  • There is a scientific logic though for looking at mixing vaccines as being beneficial
  • It is indeed possible that new variants will mean that booster doses (second or even third!) might well come from a different vaccine
  • At the very least, studying  mixing of vaccines is sensible, if only to prove their success rates are just as good

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New data on AstraZeneca vaccine:

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

Yesterday (2nd 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%


  • 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


  • 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


  • 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


  • 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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Vaccines in the elderly: yet more data today!

It’s been a very busy day keeping track of all the news emerging this afternoon, UK time, on the different vaccines! In this second but short post today, I provide an update on the European decision on the AstraZeneca vaccine and give very brief comments on the Janssen and Novovax vaccines.

EU decision on AstraZeneca Vaccine

  • The AstraZeneca vaccine is now licensed for use throughout the EU despite the German worries
  • In terms of interval between doses the license says: “The second dose should be administered between 4 and 12 weeks (28 to 84 days) after the first dose” 
  • In terms of age, whereas the EU has enabled its use in adults aged over 55, its wording is “Currently available clinical trial data do not allow an estimate of vaccine efficacy in subjects over 55 years of age


  • In terms of my post earlier today, I believe the EU is right not to have actually restricted use to adults under 55
  • Interestingly, the EU has not highlighted the data suggesting that a longer interval than 3 weeks between doses is preferable
  • The EU’s lack of specific endorsement for those over 55 was perhaps expected given their regulatory viewpoint
  • However, I do not change the conclusions in my earlier post today about the likely benefit for the elderly of this vaccine, especially given the new data from Janssen (see below)

Janssen one dose vaccine

  • Last week* I had already indicated that the results from the Janssen (Johnson & Johnson) vaccine would be published at the end of this month
  • (One of the problems in this pandemic is that the results of important research are first announced by press release and only later are the detailed results made available to the scientific community to make a detailed assessment)
  • The press release suggests a very good result clinically after one dose, with a two thirds reduction in the number of cases.
  • The press release quotes that the vaccine was as effective in those aged over 60


  • These results are exciting at this stage
  • I am unable to provide any detailed assessment of the potential role of this single shot vaccine until the detailed results are available to allow a propter scrutiny
  • I would also make the observation that the results of their preliminary laboratory assessment were only published last week. This shows the speed with which companies are very keen to publicise their clinical findings as quickly as possible!
  • There is also a relevance of these findings for the AstraZeneca vaccine, as the J&J vaccine is using an almost identical technology (with both being different to the Pfizer and Moderna RNA approaches)
  • Thus the observation that the J&J vaccine is effective in older people, would increase my expectation that further data from the AstraZeneca vaccine on older people may be similarly effective



  • This is a very different approach to vaccine design *
  • Again we only have a press release and although the results are impressive, we do need to wait for further information to be made available
  • One data item I did pick up was that there was only one case of very severe infection in the whole trial (which was in the placebo arm) so it is difficult to infer too much at this stage on this aspect of protection

*For those who are interested in how this vaccine works see my post from early November

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Germany argues too little data to approve AZ vaccine for over 65’s: what are the facts?

Yesterday Germany did not recommend the use of the AstraZeneca vaccine for people aged over 65.  The EU is going to announce their ruling today (29th January).  Given that the over 65’s are the most vulnerable, and the first target for vaccination in most countries, this is a disturbing conclusion.  

Its potential impact is all the greater as the production of AstraZeneca vaccine is planned to be the largest in the world, in part because of its low price and the fact that AstraZeneca have agreed to deliver it at cost.  In this post I consider what conclusions can be drawn on the success of the different vaccines in older people.

The challenges of the clinical trials

  • All the vaccines being licensed for widespread use require proof of both safety and benefit 
  • That proof is based on a comparison in large trials between the active vaccine and a placebo
  • Companies doing these trials have to plan to study enough people, and to have long enough follow up to produce meaningful results
  • There ae complex statistical calculations when planning a trial to ensure that enough people are recruited to provide accurate estimates of how well the vaccines work
  • Given the urgency of the situation regarding the development of Covid-19 vaccines, all companies wanted to get their trials completed as quickly as possible
  • All companies realised they needed to recruit across broad sections of the population but that the overall number might not be sufficient to provide accurate answers for each sub-group.
  • With all these trials, the “headline result” is the outcome in all the trial participants
  • Subgroup analyses are then done say by age, but accepting that within each of these subgroups there may not have been sufficient numbers recruited to answer the detailed questions 
  • Even ignoring  age (see below) we can’t know from the trials for example how the vaccine works in people of different ethnicities, with different levels of obesity etc
  • The aim is that once the vaccines are licensed, ‘authorities’ will be able to collect data on much larger groups of individuals in all kinds of subgroups, to provide more detailed answers
  • The challenge for regulators is that they have to deal with the data they have and make assumptions about how far the data from say age subgroups is sufficient to allow a wider license  

What were the data from older age groups  in the clinical trials?

  • Let me be absolutely up front and say that the numbers in older age groups recruited to the AstraZeneca trials were much lower than for the Pfizer or Moderna trials
  • AstraZeneca’s initial programme was to focus on the under 55s. It was the first company to start Phase 3 trials and as is common practice, early studies on vaccines often start with recruiting younger, healthier volunteers 
  • We should also note that as people age, they accumulate other health problems and it is typically only the fitter older people who are both allowed to, and actually volunteer to participating in clinical trials.
  • Thus, the older people who do participate may not be representative of the general population of older people
  • Nonetheless AstraZeneca had far few older people than the other companies on whom to study the effects of their vaccine 

What did the data show on the success of the vaccines in older people?

  • AstraZeneca said in their publication of the trial results “vaccine efficacy could not be assessed but will be determined if sufficient data are available in the future”
  • The data from Pfizer showed the following:
  • Two obvious points:
    • The number of cases of Covid-19 that happened in the placebo group was very small, especially in those over 74, thus we cannot have very accurate estimates of benefit in that group  
    • On the data that do exist, the vaccine was obviously very successful in reducing cases in the over 65s
  • Although the data are not repeated here, the level of protection was similar in those over 65 to the over 90% protection seen in the much larger groups of participants below that age
  • The data from Moderna showed the following:
  • Conclusions are very much the same as with the Pfizer vaccine.  The rate of reduction of cases (86%) was just a little lower than the 95% seen in the younger participants 

Are there other data to suggest the AstraZeneca vaccine is successful in older people?

  • Before embarking on the large scale clinical trials, AstraZeneca and the other companies undertook studies on the level of immunity following vaccine 
  • These were complex laboratory studies to see if the vaccine would produce the necessary  high levels of immunity in the blood samples tested
  • The blood results were very reassuringly positive, which is why the companies then tested whether this would be translated into reducing the number of cases as discussed above
  • I have gone back to the blood results data from the AstraZeneca vaccine early studies to see if there was any influence of age on the level of the immunity achieved.
  • These are the data on the antibody response, looking only at antibodies that would ‘neutralise’ the virus
  • This is what I found:
  • There was no reduction in the level of the antibody response in those aged 70 and over
  • I then looked at the other part of our immune response to vaccines: – the T cell response – which might be more important – and this is what I found:
  • Again no evidence of a reduction in this component of our vaccine produced immunity
  • Thus for the AstraZeneca vaccine the immune response was not reduced by age in the people they studied


  • German (and may be European) regulators are right in saying that the data are too limited to say that the AstraZeneca vaccine is successful in preventing clinical infection in people over 65
  • As I have shown in this blog previously, the AstraZeneca vaccine, given in 2 doses 12 weeks apart, achieves an 80% reduction in clinical cases in people under 65
  • All the 3 licensed vaccines – by targeting the spike protein – are working in the same way
  • The Pfizer and Moderna vaccines work equally well in preventing clinical infection in people above and below age 65, but the numbers were still too small to be confident about the accuracy of the estimates
  • The AstraZeneca vaccine produces a substantially more than adequate immune response in laboratory testing which was very similar in all age groups
  • Taking all this into account, I believe the UK regulator, under its emergency powers, was right to conclude that on balance the AstraZeneca vaccine was likely to be effective in those over 65
  • Obviously we will get more data as the vaccines are rolled out for general use, although these data are much harder to interpret when not in a randomised trial 
  • And yes, I would be happy to have the AstraZeneca vaccine (I am older than 65!)

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