Categories
Covid-19 Vaccines

Oxford Trial resumes

As I mentioned in my recent post the case of transverse myelitis in Oxford Vaccine trial would be reviewed by the trial’s Data Safety and Monitoring Board and the UK regulator. The case has now been considered and both bodies have given the green light for the vaccine trials to proceed.

A press release announced:

“The independent review process has concluded and following the recommendations of both the independent safety review committee and the UK regulator, the MHRA, the trials will recommence in the UK.

The independent review process has concluded and following the recommendations of both the independent safety review committee and the UK regulator, the MHRA, the trials will recommence in the UK.

We cannot disclose medical information about the illness for reasons of participant confidentiality.We are committed to the safety of our participants and the highest standards of conduct in our studies and will continue to monitor safety closely.

Comment

  • This is not unexpected nor unreasonable given there was only a single case of this complication among all the people in the trial, although the authorities have responded very rapidly.
  • I had also made the assumption that the complication occurred in a volunteer from the group who had received the active vaccine of the trial but this may not have been the case
  • Indeed the trial group of the affected individual had not been disclosed
  • Possibly that person could have been in the inactive vaccine group – which might explain the rapid response to lift the pause
  • Hopefully there will be no further cases of transverse myelitis!

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Covid-19 Vaccines

AstraZeneca vaccine ‘pause’: why and what now?

Yesterday AstraZeneca called a pause to the use of the novel Oxford developed vaccine. It will be investigating one of the UK participants in the clinical trial programme who had developed a rare condition. In this post I outline what the pause means, describe the process leading up to the announcement and consider what may be the implications for the future of the vaccine.

Oxford Vaccine Clinical Trials Programme

  • Readers, I am sure, will be aware that at the end of July the Oxford team published results from a trial of 1077 young adult participants, 543 of whom had had the new vaccine. 
  • That study showed an excellent response in terms of immunity with only moderate, and easily controlled, side effects
  • The next phase of the vaccine development programme involves  a much wider series of studies in four separate age groups:
    • 5-12
    • 18-55
    • 56-69
    • 70 and over
  • Those studies are testing both a single dose of vaccine and a double dose – 4-6 weeks apart
  • Recruitment sites are in the UK, South Africa and Brazil
  • I believe that maybe 15,000 people have been recruited to these studies 
  • A further site in India was about to start recruitment in the next weeks
  • Only two weeks ago the National Institutes of Health announced a trial of the Oxford vaccine in 30,000 subjects in the USA 

What does the pause’ mean?

  • As it says ‘on the can’, worldwide there is a presumably temporary ban on any further use of the vaccine
  • This applies to all the studies that are still actively recruiting 
  • All subjects who have already been enrolled in any of the studies above will remain in the trials, (and will continue to be followed up to identify their risks of getting Covid-19  infection or any serious side effect).

What initiated the pause?

  • There is relatively little information in the public arena –  this is not unreasonable and the pause only achieved widespread publicity because of the global interest in this and related vaccines
  • At around 11:00 pm on 8 September, a tweet from AstraZeneca announced the case of a ‘potentially unexplained illness’ in one of the UK participants
  • On Twitter this is reported as being a woman with an ‘inflammatory neurological disorder’ who is now said to be recovering.  The exact nature of this condition can only be known to the investigators.  There are two neurological conditions that rarely can follow vaccine
    • The first  is transverse myelitis which is an inflammation of the spinal cord.  A case of this condition may have developed in a previous volunteer to the Oxford vaccine study, but which did not require medical attention.
    • The other disorder is Guillain Barré syndrome which can follow flu vaccine (but also influenza)
  • The pause would have been triggered (again I assume) by the UK trial’s Data Safety and Monitoring Board (DSMB)
http://www.ukcab.net/resources/clinical-trials/guide-for-cab-members/page-16/
  • All trials internationally must have a DSMB, independent of the researchers and any companies involved.
  • The DSMB will of necessity be notified by the researchers of any adverse events that occur in the trial participants. The DSMB can then ask for further information about the case or cases
  • The trial researchers will not know which of the participants received the active vaccine and which received the inactive comparator vaccine
  • The DSMB can ask for that participant’s status to be unblinded (ie active or non-active vaccine)
  • I assume that this particular woman must have been in the active vaccine group
  • Given the enormous public interest I then speculate that the DSMB, in discussion with the company and the researchers, felt that the vaccine should not be used further, pending investigation as to the likelihood of a relationship between the vaccine and the neurological disorder

How often does this happen?

  • Clinical trials involving very large numbers of individuals are by design likely to result in some of the participants in either group developing various serious illnesses by chance alone.
  • At the end of the trial, it would be necessary to compare between the two groups to see if those in the active vaccine group had an excess of any of these illnesses
  • In this current announcement, it would appear that the participant had an unusual  illness, and that there was a biologically plausible link to the new vaccine
  • Again, given the large number of people studied, the occurrence of one or even a handful of cases of unusual conditions might be expected.  I do not know how often one case has led to a pause, but  say 3 cases would not be an unreasonable threshold.

How can or will the pause be ended?

  • Proving a link between the vaccine and any  very rare serious complication is not easy 
  • Extrapolating from one or even two cases at this stage is thus speculative at best
  • The company has taken this report seriously and suffered a modest stock market reaction as a consequence 
  • There is a universal desire for vaccines such as the Oxford one to succeed 
  • The reasonable expectation is that the Oxford vaccine (and probably the other similar ones) is successful at stopping the infection without significant side effects for the overwhelming majority of people.
  • How the pause will end is honestly difficult to answer, and this may also depend on the decision of government regulators
  • Then, as always in this situation, there would need to be a debate about the balance of risks say between the risks of serious complications or death from the  infection and (say) a 1/10,000 risk of a serious vaccine complication

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Covid-19 Vaccines

Which vaccine is going to win the race?

Given so many vaccines are being tested, how will this be decided?

Vaccines are now the best hope for ending the pandemic.  Yet there are well over 100 vaccines at various stages of development around the world.  Why so many? Are they in unnecessary competition? Although much of the publicity in the UK and USA is around these countries’ vaccines, it is Chinese research that has been filling the scientific journals over the past month.  In this post, I give a brief overview of the different approaches and how  a decision on which one to use might eventually be reached 

What is a vaccine?

I like the CDC’s* definition: “A vaccine stimulates your immune system to produce antibodies, exactly like it would if you were exposed to the disease. After getting vaccinated, you develop immunity to that disease, without having to get the disease first”

*The USA Centre’s for Disease Control 

Historical note

  • The first vaccine was created by Edward Jenner who noted that milkmaids did not get smallpox but had the disease cowpox.
  • The skin blisters looked similar to smallpox, but cowpox was much milder.  
  • In 1796 Jenner took some fluid from the cowpox blister of a milkmaid, gave it to an 8 year old boy.  He then (bravely!)  inoculated the boy with fluid from a smallpox blister  and thankfully the boy did not develop smallpox
  • The virus that causes cowpox is the vaccinia virus, hence the now familiar term vaccine
  • The vaccine research unit in Oxford is named after Jenner

Covid-19 vaccine development  in China

  • Not surprisingly since China had the first outbreak, and they determined the genetic code of the virus, they have been at the forefront of developing a vaccine 
  • Three Chinese organisations (Research Institutes in Wuhan and in Beijing and the company Sinovac)  have been testing vaccines which are a mild version of the Covid-19 virus. (This has been the standard approach to producing vaccines for many diseases, such as measles) 
  • Another company, CanSino, has tested a vaccine using a different (and safe) virus but altered to produce the CoVid spike protein (see below).  This did produce immunity but had  quite substantial side effects.  Nonetheless, the Chinese have said that it is now OK to use in the military 
  • These Chinese studies have been quite small and researchers there do not have the tradition of the network of hospitals to run large scale clinical trials
  • A further problem for the West is that China does not have the same stringent government  requirements to prove success and safety

How are vaccines being developed in the West?

  • The aim of most of the vaccines is to deliver a safe form of the spike protein of the Covid-19 virus (the bit of the virus that causes all the problems)
  • There are 3 different approaches for such a vaccine based on the spike protein  (all very clever and unimaginable a few years ago)  
Approach*How spike protein produced
RecombinantMade outside the body in laboratory
RNAMade by a safe virus inside  body in one step
DNAMade by a safe  virus inside  body in two steps

*For those who are interested, more details of these approaches are at the end of this blog

In what ways are these approaches different?

  • Recombinant vaccines follow a well-established technology used for other vaccines whereas the RNA approach is completely novel and thus untested in the real world
  • The only widely used DNA vaccine is the one developed for Ebola
  • RNA vaccines may be more resistant to any mutation in the virus
  • Recombinant technology is easy to scale for mass production
  • RNA vaccines can be very stable for storage  and cheap to produce

What we don’t know?

  • Whether  these different approaches will vary in how effective they are in producing immunity and how long it lasts for
  • Theoretically these approaches may vary in their safety profile

Who’s involved

  • There is no shortage of major international pharma companies involved! 
  • Many are working with research institutes directly on development and/or clinical testing
  • Others are providing the capacity, once a vaccine has been licensed, to do the necessary large scale production 
  • These company links are necessary.  At the moment, the companies are talking about cooperation and not-for profit production –  as long as there is government support for developing vaccines that are not used 
  • It will be interesting to see what happens when, and if, the market place opens with multiple clinically successful vaccines!

How to decide which vaccine is best?

  • These different vaccines are each only being compared to  an inactive vaccine and not against each other 
  • Although we can compare the results on both the effectiveness and safety reported from each study, such a comparison may not be a fair reflection of their relative success
  • Epidemiologists would be cautious comparing between two vaccines if (say) vaccine A was tested on volunteers in Sweden and vaccine B tested on volunteers in New York
  • Thus, a reasonable question is: “should we not try and prove one is better than the other(s) in  a ‘head to head’ comparison?”
  • That won’t happen for several reasons
    • It would be impossible to have one study involving all the available vaccines so in theory we would need multiple trials comparing different pairs
    • Comparing two active vaccines to see (for example) if one prevented 10% more infections than the other would need much larger numbers of volunteers than studies of an active versus an inactive vaccine 
    • It would thus take too much time to have a result
    • There are political and industrial considerations, given all the parties involved  (although these are possible to overcome)
  • Hence we won’t really know which is the best vaccine (at least initially)

What will happen next?

  • The West will probably ignore the results from the Chinese vaccines
  • Early studies from all the approaches suggest that the different Western vaccines appear to be safe and also without major short term side effects (these two are different). 
  • Thus far  all these approaches also produce a reasonable level of immunity. (See for example, my post on 20 July the Oxford vaccine)
  • We need to await the results of the large ‘Phase 3’ studies which  government regulators use to give the green light to start widespread use.  (Though my post of 13 August gave the case that has been put forward by others not to wait for such results) 
  • With luck definitive results from these studies will be coming out from the end of this year, to say first quarter 2021.
  • The pressure will then be on for different countries/companies/manufacturers to start widespread use 
  • Over the next 12 months independent researchers will also start undertaking sophisticated statistical analyses comparing the Phase 3 trials from the different vaccines and attempt to draw conclusions about which approach is best.
  • Countries may, but probably will not, change which vaccine is used if they have already started a vaccination campaign using a safe and effective vaccine, even it is not the most effective
  • In addition, all the companies/administrations will start collecting the data on what happens when the vaccines are in widespread use: what are the short, medium and long term side effects and how long do they last?
  • This is a story that will run and run!

Some details about the different approaches of vaccine development

  • ‘DNA Vaccine’: Made by adding into a harmless virus just that part of the Covid-19 virus gene that makes the spike protein. The spike gene in this vaccine then produces large amounts of the spike protein via a second genetic step involving RNA
  • RNA vaccine’: The process by which  DNA produces proteins is via a second genetic process involving a messenger called RNA.   RNA vaccines are the actual RNA message which   deliver directly the genetic instruction to produce the spike protein
  • ‘Recombinant vaccine’: Rather than relying on the vaccine to stimulate the production of the spike protein in our cells, a recombinant vaccine actually contains the spike protein which is manufactured genetically in the laboratory
Categories
Covid-19 Vaccines

Concern about when we will know if a vaccine is successful.

What do Vladimir Putin and 15 Nobel Laureates have in common?

Yesterday Vladimir Putin announced that Russia was poised to commence using a vaccine based on early positive results.  This suggestion has been widely derided in the media given the inadequacy of the testing on that vaccine.  Yet two weeks ago 150 scientists and ethicists internationally, including 15 Nobel prize winners, signed an open letter arguing that the current approach to vaccine testing was wrong and demanded a speedier process. Is the planned approach to testing by Oxford and other vaccine research groups too timid? 

What do we know so far?

As has been widely reported, and described in this blog:

  • Vaccines suitable for human use have been produced
  • In younger volunteers they are safe (at least in the short term)
  • They produce a substantial immune response which hopefully should be sufficient to stop infection

What we don’t know yet:

  • Whether in practice infection will be stopped
  • How well the vaccine works in older people
  • How long the vaccine will continue to work after it’s been given
  • (None of these have been tested in the Russian vaccine)

The ‘Phase 3’ study 

  • To assess in practice whether any vaccine ‘works’, a study needs to be undertaken- the  so called ‘randomised clinical trial’ – which compares the rate of developing an infection between 2 groups: half given the vaccine and the other half an inactive vaccine.
  • The comparison is needed to calculate the size of the reduction in infection rate in those given the active vaccine  from the ‘background rate’ provided by the inactive vaccine group
  • In such a trial, the volunteer does not know which group they belong to, ensuring that the two groups behave similarly in their day to day behaviours and reporting of any symptoms 

What’s the problem?

  • Basically, even if the vaccine ‘works’ by preventing infection it might take more than 6 months from now to prove this.  My justification for this conclusion can be found at the bottom of this page

What was the suggestion from the open letter signed by the Nobel Laureates?

  • Given the concern that we would need 6 months, or even longer,  to show success, that would mean we would be well into next year before any vaccine programme could be started 
  • This delay, the letter argues, leads to avoidable numbers of deaths, severe illnesses and more damage to economies globally
  • Their proposed solution is a push for ‘challenge testing ‘
  • I’ve mentioned this previously, but in summary with this a relatively small number of volunteers are given the vaccine, tested for their immunity, and then exposed to the virus.  Hopefully most would not get an infection, hence proving the vaccine’s success
  • Such a study would be much smaller and is not dependent on the background rate
  • If the volunteers are young and healthy, even if they contacted the infection, they would probably not develop any complication of Covid-19. 
  • 30000 volunteers globally have signed up and are ready to go

Is this ethical?

  • The letter has been signed by many distinguished ethicists 
  • We can’t predict now even in this very selected group, whether there is still a risk of dying from a catastrophic immune response

And also

  • We would not know if the vaccine was successful in elderly people or those who had other health problems 

My own view? 

An interesting dilemma.  This would be a major departure from our normal approach to testing vaccines for diseases where there is not a treatment.  There is nothing normal about this pandemic though but also the speed of the development of the vaccines is breath-taking. The cautious view is that societies should continue with all social distancing and other measures for a few more months and just be patient about the vaccine.  If this first wave does not settle down though, then maybe the pressure for a more rapid approach to getting a vaccine out will grow  

How I calculated that 6 months might not be long enough

  • As the Oxford and other research groups openly admit, if the background risk of infection is very low it may be impossible to prove the new vaccine is successful in preventing infection
  • This  trial is studying around 12000 patients: 6000 in each group
  • The volunteers  were recruited in May and June and are being followed to  determine how much lower the infection rate is  in the active vaccine group
  • Obviously, the more months of follow up , the greater the number of new infections and hence the greater the chance the trial will have enough numbers to prove vaccine success.
  • I have attempted to see how many months will this take.  I have looked into  how likely is it that they will get a positive outcome in (i) 3 months and (ii) 6 months 
  • In doing this calculation I have used the survey data that suggest at the moment the background rate of infection  in England is 2/10,000 population per week.
  • This is an estimate but could be as high as 5/10,000 or as low as 1/10,000. 
  • I have taken as a positive outcome that the vaccine would need to reduce the rate of infection by at least 70%.  (This is the average for influenza vaccine but may be pessimistic.) 
  • I have used standard statistical methods to assess the chances of the trial showing the vaccine at 3 and at 6 months and  for each of these 3 estimates of background rate.
Background infection rate/weekLowest
1/10,000
Middle
2/10,000
Highest
5/10,000
3 month trial 
6 month trial
  • What this table shows that at the lowest estimate of background risk the trial would not show a benefit even at 6 months.  Benefit will only be shown at 3 months if the background risk is at an (unrealistically high I believe) level of 5/10000/week
  • In fairness if the vaccine success was as high as 90%, then the trial would be successful at 3 months for the middle (but not the lowest) background estimate. 
Categories
Covid-19 Vaccines

Promising new data on Oxford Vaccine

Data published today has given promising results on the Oxford vaccine

The Lancet published the first results from the Oxford vaccine study today. The results look promising.

Safety

  • 1077 people mean age 35 were studied, of whom 543 received the new active vaccine. A small number (10 subjects) received a booster dose
  • There were large numbers of mild reactions including headache, fatigue and other flu like sympotms, all of which lasted only a couple of days
  • Paracetamol taken before vaccination reduced some of these side effects
  • There were no serious reactions
  • In the 10 subjects who received a booster vaccine, the side effects were less severe with this second dose
  • The dose of virus in the vaccine was quite high which was considered necessary to produce rapid immunity. (I am not sure if a lower dose had been used it would have produced less severe side effects with the same benefit in terms of immunity-see below)

Effectiveness

  • This report focused on safety, but a small proportion of the participants had various laboratory tests to assess whether the vaccine would produce the desired immune response
  • There was a very good immune response in terms of the level of antibodies, which after one dose had peaked at 28 days .
  • The antibodies were also shown in the laboratory to be ‘neutralising’ ie capable of preventing the virus from causing disease. This was 100% the case in the small number that had a booster dose
  • For people with pre-existing evidence of antibodies (from natural infection), their immune response was enhanced by the vaccine

Comment

  • The authors have been rightly cautious about these early results and the issues I mentioned in my previous blog about vaccine remain
  • It is interesting to see the results from giving a booster (although very small numbers). This suggests that if and when this vaccine is introduced, a booster may be part of the vaccination routine
  • It is good news that the immune response produced by the vaccine was ‘neutralising’ – this one of the outcomes the study needed to confirm
  • The results are from healthy young, predominantly white, volunteers. The level of side effects was acceptable in that group but needs to be studied of course in older people (which is happening).
  • Similarly we await how suucessful the vaccine will be in terms of achieving an immune response in the elderly
Categories
Covid-19 Vaccines

How near are we to a successful vaccine?

Despite the relaxing of the lockdown measures, many people are still too scared to go to restaurants/travel on the Tube/go by plane/hug their family.  The most common aspiration is that the introduction of a successful vaccine will lift all these worries.  How near are we to achieving that aspiration?  On Tuesday I attended a webinar given by Professor Andrew Pollard, Director of the Oxford Vaccine Group, who gave an update on CoVid vaccines in general and the Oxford vaccine in particular.  These are my conclusions based on what he said, and what I’ve read subsequently.

How many vaccines are being tested?

This is an easy one, in addition to the Oxford vaccine, there are 22 other vaccines worldwide that are being tested in humans and a further 140 being tested in animals.

How do the vaccines work?

Many (including the Oxford vaccine but not all) work on finding a harmless way of introducing the spikey bit of the CoVid virus into the body, which will generate an antibody response.  (It is the spikey bit that causes the problems – as this allows the virus to attach itself to all types of cells and tissues within our bodies.)  Thus, when faced with the real CoVid virus, the body will generate antibodies against its spikey bits and neutralise it.  What the Oxford group are doing is to apply some fancy genetics and incorporate the genetic code to produce the spikey bit into a harmless virus.  The vaccine is this genetically modified virus.  Other vaccine laboratories are finding different ways of producing antibodies.

Is it safe?

That is obviously the most important question.  Of course, all vaccines are tested in animals but that doesn’t guarantee safety in humans.  The first stage of the Oxford clinical programme is to test for its safety in humans.  My guess is that the results of that will be published very soon (ie a few weeks). (See below for stop press on results from the USA vaccine).  I also guess that if there had been a major safety concern with the volunteers who have already participated, and who are being closely monitored, that would have become apparent.  Whether there are longer term hazards from the vaccine can only be determined by long term studies!

Assessing an antibody response?

The result of whether there is an antibody response in the human volunteers will emerge at the same time as the safety information mentioned above. What will be important is to know not only what proportion of the population are likely to have an antibody response, but also what is the size of this response (ie are ‘enough’ antibodies produced) and is it possible to predict who will, and who will not achieve, an adequate response.

One concern is that those most at risk from the complications of the infection are the elderly and as we age the response to vaccines diminishes.  In the second phase of the Oxford  programme the vaccine is being tested in people aged over 55 and those results will come a little later.

If there is an antibody response does that mean protection against infection?

That is a more challenging question and one that will be determined by the larger trials Oxford (and others) are carrying out in the UK and worldwide. In order to quantify how successful the vaccine is in protecting against infection, these trials need  also to discover what the infection rate would have been if people had not been vaccinated. To achieve this, a random half of the volunteers are given a safe vaccine (‘dummy’) that has no action against CoVid. The goal is that the rate of infection in people given the new vaccine is lower than in those treated with the ‘dummy’ vaccine.  

Of course, the rate of infection may be even a lot lower than in the comparison group, but the public will be hoping for complete protection.  Whether this is possible is not known.  It may not be a fair comparison, but the annual flu immunisation may only reduce infection rates by 70%.

The other challenge for the researchers doing the trials is that if the rate of infection in the general population is very low, then there may be too few people developing the infection in the dummy vaccine  group.  It would then be very hard to show whether the active vaccine is effective.  It is a paradox, but we need a high rate of infection in the general population to show the vaccine is successful.  If the population are too successful at preventing community transmission of infection by measures such as distancing and face masks then it will be that much harder for the trials to show benefit!  

One option, perhaps, could be considered for ‘high risk” groups, such as care home residents and health and care staff.  As the vaccine is being produced anyway (see below), therefore assuming it is safe (at least in the short term) and it produces an antibody response, perhaps this would be enough evidence  to justify starting a vaccination programme. This might be particularly for high risk groups and need not await the results of the larger trials to emerge.  It would still be necessary to monitor the rates of infection. 

How long would any protection last?

Again, this has to be studied and cannot be predicted with any certainty.  Antibody response does wane over time; but this may not be a major concern. Vaccines work by producing an immune ‘memory’.  Thus, if vaccination is successful, when faced with the real virus, the immune system ‘wakes up’ and start producing enough antibodies.  This ‘wake up’ also stimulates a separate part of the immune system that produces cells to attack the virus 

One theoretical concern is that the virus mutates and the vaccine, whilst effective against the ‘original’ virus, is not effective against any new version.  This is why for example flu jabs need to be repeated each year against the new strain.  Interestingly the consensus opinion is that the CoVid-19 virus does not mutate, or mutate sufficiently to be an issue. 

If any vaccine is not completely protective or does not last, is there anything that can be done?

It is possible that giving two doses would achieve a stronger immune response, which is well known in other vaccines. Similarly, giving a booster vaccine, after some interval could also prevent waning immunity, again this is well known from other immunizations eg tetanus. I am sure studies on this will be started once we know we have a partially successful vaccine.  What is also interesting is whether a “two-hit” policy might work.  For example, if two vaccines, which have a different approach, but are both targeting the spikey bit, when given in combination that might produce a better response.  The vaccine developers in Oxford and other places I know are in communication about this.

This all sounds like a long process when would the vaccine be available for widespread use.

Widely publicised is the linkup between Oxford and the drug company Astra Zeneca to produce possibly 400 million doses of vaccine for Europe by the end of 2020 and with other tie-ups 2 billion doses worldwide.  The vaccine is thus being produced in these quantities in the expectation it will work.  If we waited until the trials have reported their results to kick start the manufacturing process, then there would be significant delays.  Most people would take the view that it is worth the financial risk. 

OK so when can I be vaccinated?

We should all take note that it normally takes 5-10 years from the start of a research programme to develop a completely new vaccine.  The CoVid vaccine research groups around the world are attempting to do this within a year.   Even optimistically, this might still mean waiting several more months for a successful vaccination programme to be rolled out. Waiting several months for a successful vaccine before returning to any kind of normality may  be OK for some, but would be unacceptable for others –  and for the economy – in areas with a very low risk of infection.

STOP PRESS

Interestingly a report published in the New England Journal of Medicine on 14 July of a study of the leading US Vaccine (Moderna Inc.), two doses of their vaccine, 28 days apart, produced a successful antibody response in 45 patients, although there were some with side effects. 

Categories
Covid-19 Masks Vaccines

Corona Virus-(CoVid-19): what do we know?

[First circulated 25th February 2020]

What is the virus?

CoVid 19 is one of the family of viruses, the corona virus, that causes the common cold and is not, for example, part of the influenza virus group

How is it spread?

It seems that it is mainly spread from person to person and not via droplets hanging around in the air.  Although it can be spread direct into your nose, the hands can be a major source of infection: ie if you touch your face after your hands have had contact with the virus from an infected person

How infectious is it?

Experts probably don’t know exactly. There are two meanings of “how infectious”?

  • How many individuals can one person infect?  On average this appears to be quite small and a figure of 2-3 people get the infection from any one other affected person seems to be the major conclusion.  But this is  obviously influenced by how much contact such an individual has.  The idea of a ‘super infectious person’ is probably a myth
  • If you are not immune and you are sufficiently exposed to the virus, how likely is it you will get the infection?  Again, this is not clear, but seemingly the risk is  very high as few people will be naturally immune and the virus is quite effective

Are people infectious before they know they have the virus?

This appears to be the big problem and say differs from other corona viruses-if you have a cold you are only infectious when you have symptoms and are shedding the virus.  CoVid-19 has a particular property of fooling the body’s first line of immune defence when it enters the nasal airway.  The body’s first line defence is thus not activated and the virus multiplies and sheds.  So, for around 3 days after contracting the virus, the  infected individual, who will be feeling fine,  will be shedding virus into the air to those who are in close contact 

Are masks effective at preventing spread (should I wear one?)

Masks are now ubiquitous in China and other countries in South East Asia.   Obviously, carers and close family members of affected people should wear masks. There is now a world shortage of effective masks (most are made in China).  Indeed, the NHS is worried that there may not be enough for its own workers should a major epidemic take hold.  Experts say for low risk countries, such as the UK, it is unnecessary for normal healthy people to wear a mask to prevent them getting infected  All websites emphasise the importance of proper hand washing (with soap and water) and not touching the  face especially when having been in contact with a person with symptoms.

What are the consequences of getting an infection?

As the newspapers and other media report, the mortality rate is around 2% which is similar to that for normal seasonal flu.  Indeed, it might be lower than 2% as many mild cases are not reported.  But what about the other 98%. For most, the symptoms will be like a mild cold and chest infection. But, the problem is that the virus, not stopped by the body’s fist line of defence, then penetrates deep into the lungs and can cause pneumonia and other chest infections. This virus particularly likes the cells that line the lungs and sticks to them. The data from China suggest that perhaps 1 in 7 will have significant pneumonia.  Again, most such people will recover from a viral pneumonia.  There are a few people who then mount an exaggerated immune response to the infection in their lungs and then there is a massive battle between the virus and the immune response which can be very serious and probably explains the young deaths reported

Are any people specifically at risk of having a bad time?

As you might expect, elderly people, especially those over 80, with pre-existing lung disease and who have weakened immune systems are more likely to have complications and not be able to mount a good if delayed immune response.  But what about ‘normal healthy people?  The short answer is that the experts do not know why most previously healthy people have a mild disease while others  can get a significant pneumonia.  Interestingly, men seem to have worse disease (twice as likely to get complications – but this has been seen in other epidemics in the past eg SARS and MERS).  There may be a genetic risk, but what these are is not known

Why don’t some of the existing anti-viral drugs work?

Sadly, the drugs that were tested for treating other influenza outbreaks such as Relenza (Zanamivir)and Tamiflu (Oseltamivir) are  not likely to be effective against CoVid 19.  Indeed, despite government’s stockpiling millions of doses following the 2004 outbreak, the clinical trial evidence was even very weak for that and related epidemic.

An Israeli company has started an urgent clinical trial to see if they have an effective drug for the small number of people with acute severe pneumonia, but that is based on stopping the fight between the immune system and the virus and would not be used for ordinary infection 

Why can’t they get a vaccine quickly?

There is now a vaccine in trial against MERs, a related corona virus, which does seem to be safe and effective but will need to be tested on many more people.  The technology used to develop and test the CoVid-19 vaccine will be similar but honestly, it will be at least a year before large scale trials can begin I would imagine.  And remember, in a disease that for most people is very mild, if the vaccine has significant side effects in anything more than a tiny minority then its risks will outweigh its benefits

If people get infected are they then immune from further corona viruses

Again, not known, but based on SARS, probably some immunity but not life long