Anti-viral drugs Covid-19

Could drugs be a solution to the virus?

Covid-19 would be less of a worry if there was a very effective treatment

It is an obvious fact that the world might not worry about the dangers of catching Covid-19 if there was an effective and safe (and hopefully cheap) drug to stop the disease ‘in its tracks’. The idea is that it could be taken when people  had the very first minor symptoms of being unwell or even when testing positive.  As a  historical parallel, in the pre-antibiotic era, infections that we now consider minor such as ear infections and sore throats could have led to life threatening complications.  The population now, though, no longer worries about such disorders because antibiotics are so effective (although the major concern of antibiotic resistance is real).  This post thus addresses how likely is it that we could get such antiviral drugs that could be similarly effective and appropriate for widespread use in Covid-19.

Comparison with antibiotics The comparison with antibiotics and bacterial infections is interesting.  In most countries those who visit their general practitioner with a  sore throat or a chest infection these days would be denied antibiotics:  the advice being that (without testing)  the illness (a) is due to ‘a virus’ and hence  does not respond to antibiotics and (b) will settle down on its own.  Thus, we have developed an acceptance  that common viral infections do not  need specific treatment and are not likely to become serious.  Covid-19 has proved the latter to be untrue, so where are we on the path to addressing the former? 

When might drugs be used in Covid-19? Drugs might be used at 3 stages

  • To stop people becoming infected after being exposed to the virus 
  • To stop the virus actively producing many copies of itself in the body and prevent severe clinical problems
  • To treat the ongoing clinical problems, and especially the complications, caused by the virus

Vaccines cover the first stage. Drugs for the third stage cover the range of drugs from simple agents that control symptoms such as paracetamol, to those used to treat and control the serious consequences and the complications of infections.  (Drugs in this class include dexamethasone that received much publicity recently as it reduced the number of deaths in Covid-19 patients admitted to intensive care units.)  

What is lacking are drugs that stop the virus, once it has established itself, from causing further harm.  Viruses work by entering our cells and then taking them over and using them to produce millions of copies of themselves.    If that process can be stopped, then if someone became infected the virus would be unable to cause much harm.  Such drugs are known as antiviral agents.

Are antiviral agents effective in other viral infections? Although many viral infections lack an effective drug to stop the virus multiplying, there are  also a large number of infections where antiviral drugs are useful.  These  drug names often end in ‘vir’.  Most widely known is acicolovir/acyclovir (trade name Zovirax), which can even be bought ‘over the counter’ for the treatment of cold sores and shingles. There are also a number of antiviral drugs that work in influenza.  These include drugs such as oseltamivir (known as Tamiflu) and zanamivir (known as Relenza).  Indeed, in the previous epidemics of bird flu and swine flu, governments spent millions stockpiling these drugs.  They were of variable benefit and in fact were never widely used. There are also now at least 20 antiviral agents that have been used to stop viral multiplication in HIV/AIDS.

Does each virus need its own antiviral drug? Antibiotics, such as  penicillin, are typically active against many different bacteria.  The range of bacteria covered by one antibiotic can vary. Some antibiotics are ‘narrow spectrum’ and active against a few bacteria , whereas some are ‘broad spectrum’ and active against a larger range.  By contrast there are very few antiviral drugs that are considered broad spectrum (apart from remdesivir, see below) and most are very specific.  Indeed, the large number of drugs used to treat the AIDS virus attack very different aspects of the virus’s activity (and indeed are used in combination).

Where to start looking for antiviral drug against Covid-19? One major hope was that there might be no need to develop a new antiviral drug, as that would take too long, but that drugs of known benefit in other viral illnesses could be also used for Covid-19.  Covid-19 is one of a family of so called RNA viruses which include those that caused the epidemics with SARS in 2002 and the MERS (Middle Eastern Respiratory Syndrome) in 2012.  It is also related to the Ebola virus which caused such concerns in Western Africa in 2014-16. 

Remdesivir is one of the few broad spectrum antiviral agents and has the potential to block the pathway by which RNA viruses multiply.  It was originally hoped it would be useful to combat the Ebola and MERS pandemics.  In practice, in clinical trials, remdesivir did not prove useful in treating Ebola but the drug was still a strong candidate to try in Covid-19. 

There have been at least 10 trials and there are now a number of studies suggesting that this drug can be useful in severe Covid-19.  The most widely published study showed that in patients who developed severe lung complications, remdesivir reduced the length of time  a patient was in hospital from an average of 15 to an average of 11 days.  Around 20% had serious side effects.  Thus, whilst useful it is not a miracle cure and the safety profile means that it is not suitable for widespread use in  people with mild disease.

Are there any new antiviral drugs on the horizon that can treat people with early Covid-19 to prevent serious complications?

As implied above most of the work has been done on reusing (or ‘repurposing’ in the jargon) existing drugs, and there is no obvious candidate.  To develop a drug from scratch that is directed towards Covid-19 will take some time.  The approach is first to study how the  virus divides and attacks human cells.  This information is then used to design drugs to block such actions.  This can be very complex work but in June research from California has achieved in 3 months what in normal times can take two years.  The research has identified the key mechanism that the virus uses to multiply in human cells and is now starting to design drugs to address this.  They will have to be tested carefully of course for safety and benefit.  Even with success at every stage, having a new drug available for widespread use must be a couple of years away.

Does resistance occur with antiviral drugs?

Like everything else the answer is ‘it varies’!  It depends on whether the virus mutates in such a way that is still causes illness but escapes the process by which the drug works.  The cold sore virus has not become resistant to acicolovir as far as I am aware, despite the drug being so widely available.  By contrast the problem for patients with HIV/AIDS is that the development of new antiviral agents barely keeps up with the development of resistance to existing agents. It is too early to know for sure whether Covid-19 virus will develop resistance to remdesivir but a study at the end of June, from India and Japan, suggests that the virus could mutate to become resistant to remdesivir.

One problem with Covid-19 is the long incubation period

The incubation period for seasonal flu is probably about two days.  Indeed, the studies with Tamiflu showed that one needed to take it within a day of symptoms appearing to have the desired effect.  Covid-19 has a longer incubation period of maybe 5-7 days and by the time that symptoms are present, the virus has already multiplied and it is perhaps too late for any antiviral drug to work.  However, recent research from Belgium using computer simulations has shown that with a robust ‘track and trace’ system which can identify individuals and their contacts with the virus, the use of antiviral drugs even before any symptoms appear can make a big difference in helping control local outbreaks


  • There are no existing drugs that are useful in treating people with Covid-19 to prevent the infection becoming serious.
  • It should be possible to develop new drugs to stop the virus multiplying  in the body’s cells and prevent the serious complications
  • This will take time to develop and especially to prove the drugs are safe and do not cause more health problems than they prevent
  • Being optimistic, strategies that combine successful contact tracing and testing with early use of any such treatments could be an alternative to a vaccine if the latter proves too difficult to achieve 

Covid-19 Risk

How common is Covid-19 (and what is my risk?)

Is the rate going down or staying the same?

Every day we are told about the numbers of deaths and the number of new cases of infection (based on those who test positive) with Covid-19. As interesting as these data are, they do not give any real indication of how likely any of us are to contract the infection and whether the rate of new infections is going down. In this post I will discuss what the current epidemiological studies tell us.

The ‘headline results’ are:

  • Approximately 1/3500 people in England in the general population have evidence of being infected currently
  • This is down from 1/450 around 8 weeks ago.
  • There are probably around 1700 people newly developing the disease every day.
  • Over the past month, the rate of new infections is levelling off.
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.


  • 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)


  • 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


  • 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
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.


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. 

Covid-19 Testing

CoVid-19: Update on Recent Information

[This was circulated on 11 March 2020. Although much is still probably relevant, at that time encouraging infection amongst younger people was being discussed to achieve herd immunity. Also, interestingly, aerosol transmission was ruled out – which given my recent post was probably premature]

What is the test being used to detect  CoVid19 infection?

The test used in the UK and elsewhere in Europe is to take a swab from the back of the throat and to determine if there are fragments of viral genetic material (RNA) present which are distinctive for Covid19.  Thus, the test determines the virus is present and not necessarily proves active infection.  This test should be able to determine the different strains of virus as it mutates in different populations. 

In China, they have also been using blood tests to determine if there are antibodies to CoVid19, which prove an antibody response to a viral infection

Can the test be positive in people who do not have the infection?

This question can also be rephrased as “are there people who carry the virus and remain well but could pass on the virus to others (asymptomatic carriers)?”

There is limited data on this question as far as I am aware.  Reports from China have identified  asymptomatic carriers who are family members or other close contacts of infected individuals who test positive for viral RNA.  These individuals are then shedding the virus without themselves ever displaying signs of illness.  Interestingly, the reports thus far suggest that while many of these may not have the illness when tested, when carefully followed up, do show signs and symptoms up to 28 days afterwards. By contrast a very few still have active virus after a month but are not ill.

I am not aware of any random population studies in the areas affected eg Wuhan to see how many people with apparently no contact with an infected individual are harbouring the virus in their throat, with no illness. 

What is the incubation period?

This has now been relatively well characterised and widely known. The period between being exposed to the virus and developing symptoms does vary but the median time is about 5 days (ie 50% of cases have developed by that time interval)  and the large majority by 7 days.  In all, 98% of those going on to have the disease  have developed it by 14 days after exposure. The 28 days reported in family members above is extreme.

If someone is infected, how long are they infectious for after the symptoms start?

That is a different question to the one of incubation but important of course.  The question is: assuming people have recovered from the illness, eg cough, cold and fever subsided, do they still pose a risk to others?

The Chinese data suggest that the time of maximum amount of virus shedding , ie the passing of the virus in droplets from the respiratory tract-nose and mouth, is in the early part of the infection.  As the days go on the amount of virus declines.  What researchers have done was to try and grow the virus from nasal and throat swabs at different time points after the illness starts. Basically by 8 days it has proved very difficult to grow the virus in anyone.  Their conclusion is to assume by 10 days after symptoms have started, assuming the symptoms have stopped, people are not infectious.  

However, the Chinese have also shown that fragments of the viral RNA can persist for days, perhaps for weeks after the symptoms have subsided They cannot grow the virus in culture and their  conclusion though is that these genetic fragments, of themselves do not indicate that the person is still infectious.  Indeed, given it has been difficult to grow the virus after 8-10 days, the persistence of the viral fragments may be of little relevance.  More research will follow for sure.

How do the authorities know how many cases of coronavirus there are?

We are bombarded by numbers of new cases every day in the media: how are those numbers gathered?  For the moment, the numbers are purely based on the reports submitted to the public health departments from the testing labs  of the number of tests which have proven positive.  For countries that have been very slow of the mark in testing (eg USA) their numbers are a woeful under-estimate.  If, and when, in UK people self-isolate at home with mild symptoms and are not tested, the exact numbers will not be known.  I assume that there may be sample surveys of some primary care practices to identify the numbers to make an estimate.  Thus, although we should expect the numbers to rise in the next days/weeks, these numbers will under-estimate the true overall number of new cases but over-estimate the proportion of the more serve cases.

Are we now clearer about the main route of transmission?

CoVid-19 in almost every case has  spread from droplets by being in close (ie 2 metres proximity) to an infected person.  There is no evidence that the virus hangs around in the air (aerosol).  So, for example it has been suggested that on  a plane, if there is an infected person, it is only those within 2 rows who are at risk!

What is the evidence that it can be spread from hard surfaces?

In addition to droplets, the media have been keen to emphasise that where such droplets land on a hard surface they can persist.  What is clearly not possible is to prove that any individual case was picked up from this route say from a particular door handle touched a week ago.  Testing hard surfaces for presence of the virus is not done routinely.  So the hard surface route being a source for any case or cases will I assume always remain an unproven possibility. The concern about the survival of virus on hard surfaces  came from work on SARS in the laboratory which showed that on hard shiny surfaces, eg metal in the laboratory, virus could be detected sometimes up to  couple of weeks after exposing the surface to the virus.  Experts thus believe that the same is likely to be true for CoVid-19.  Alcohol, dilute bleach and hydrogen peroxide all very effective at sterilising hard surfaces of the virus

When will this epidemic end?

This is the really interesting question and there are lots of unknowns.  There are a number of possibilities:

  1. Successful containment:  The virus can only be spread for person to person (let’s leave the issue of animal transmission) so in theory if all infected people are totally isolated then the virus could have ‘nowhere to go’.  This appears to be the explanation of China’s apparent success and it is an interesting experiment to see if Italy also succeeds in their drastic measures.  However, this might be a short lasting success,  if  infections persisted in other countries and then got re-introduced into a country where they thought it had been contained and people started mixing again, the epidemic could start over.
  2. Naturally die out of the virus in warmer weather One suggestion widely mentioned in the media is that (as with ‘seasonal flu’), come the warm, drier weather, the virus will struggle  to survive and will then naturally die out. Epidemiologists also suggest that in summer we are less indoors and less in close contacts with other.  SARS did disappear in a few months.  The summer reduction theory is accepted by many although it has been suggested that CoVid19 could be with is for years and have outbreaks as with seasonal flu.  Although with increasing natural immunity and a weaker virus, see below this is likely to be less serious.
  3. The virus will become weaker This is an interesting theory which suggests that as the epidemic proceeds the virus becomes weaker.  In scientific terms the theory is that viruses mutate continuously during an epidemic. Further as the virus mutates, it becomes less virulent (causing less harm).  The reason put forward is that for the virus to survive it needs to be passed on from human to human.  Thus, those humans who have the more serious disease and are isolated in hospitals or die, are less likely to pass their version virus on, and there will be selective transmission of those mutations associated with milder disease.  This is speculative but accords with data from other viral outbreaks
  4. Vaccine:  A successful vaccine would easily terminate the epidemic but as I stated earlier, that even though clinical trials have started, it won’t be available for widespread us, I suspect until 2021
  5. Herd immunity:  From discussion with colleagues, but not seen in writing, is that we should be prepared to allow (say) most ‘younger’ healthy people go about normal business, catch a mild disease and then become immune.  Once the proportion of the population level with natural immunity reaches a certain level, then the non-immune people in the population would be too far spaced for an epidemic to take hold.  Intriguing  idea, but probably not politically acceptable and, or too risky as cannot assume only the healthy will contact the infection and,  in terms of the numbers of complications, health services would be unable to cope 
  • Can you get it from your pet?

To finish on  a lighter note, there has been a single case reported from China of transmission from patient to their dog.  Most commentators have dismissed the significance of this

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


Some thoughts from earlier on in the pandemic

I am posting some of my earlier newsletters about the virus. Some of the questions have now been answered. On some issues my thoughts are different now., whereas on others our knowledge remains unchanged. It is interesting to look back

Covid-19 Mortality

Mortality from CoVid amongst Jews

[First circulated 29th June 2020]

Widely reported in both the Jewish and non-Jewish press was the high mortality from Covid amongst Jews in England and Wales.  This brief paper summarises the data, what is known and what is not known.

The study data : 

The Office for National Statistics in England and Wales linked the names on the death certificates that mentioned CoVid occurring between 2nd March and 15th May to those individuals’ self-reported religion on the 2011 census

The denominator was the total who self-reported one of the nine different religious groupings (including no religion) in that census

For each person who died the research also extracted from the census data:

  • Age
  • Gender
  • Self-reported ethnicity-ie white/non-white (not relevant for Jews but is important in comparing with data from Muslims 
  • Various indices of socio-economic deprivation
  • Self-reported health 

Comment: The number of Jews from the 2011 census amounts to 0.5% of the population.  Obviously like any estimate it is subject to errors. 


The research calculated the numbers of deaths per 100,000 in each religious group, separately by gender, overall and divided into those above and below 65.

They then calculated a full age-adjusted analysis to  compare these rates with the rate in Christians and other religions (including those who declared no religion).

Comment: The analysis was a standard epidemiological analysis.  One concern might be that using Christian as the comparator might be based on a very selective part of  the population.  In fact, 60% of the England and Wales population declared themselves as Christian in 2011 compared to just 7% who did not state their religion

The results 

There were a total of 453 deaths in people who were identified as Jewish on the 2011 census, 23 were aged 64 and under  and 430 above that age.  268 were males and 185 were female.  

The headline rates of deaths per 100,000, after adjusting for the age distribution of the population were  as below:

 Males: Females: 

* Note that the death rates for those with no religion or not prepared to say were similar  to the Christian population

  • Restricting the data to just the population aged over 64, this was the ranked order of deaths, taking account of the age structure, by religion
Ordered by highest death rateMales: Females: 
  • Restricting the data to just the population aged 64 and under this was the ranked order, taking account of the age structure of deaths by religion
Ordered by highest death rateMales: Females: 

 * Note that the number of female deaths under the age of 65 was too small for some religions (including Jewish women and thus age-adjusted rates were not calculated  

  • After allowing for socio-economic and other indices of deprivation and self-reported ill health at the 2011 census this was the ranked order:
Ordered by highest death rate Males: Females: 

Comment: There is no doubt that Jews have a much higher death rate from CoVid than the background Christian population and indeed were similar to, or higher than, other religious groups This analysis takes into account that some of the differences in death rates may reflect differences in factors such as poverty and overcrowding.    Indeed, the death rate in Jewish males was still approximately twice that in Christians.  Although British Jews as a group may be better off economically, there are those in the growing Charedi community who are poorer and more overcrowded.  This analysis takes account of these differences 

The above analysis was repeated after allowing for self-reported ethnicity ie white/non-white.  This was the result:

Ordered by highest death rate Males: Females: 

Comment: This in some ways is the most interesting result.  Whilst Jews virtually always describe themselves as being of  ‘white ethnicity’ this is not true for Muslims.  (Detailed figures are available). After allowing for the ethnicity question, the effect of Muslim religion is much diminished.  The interpretation is that it is not the Muslim religion that is associated with the higher death rates but the ethnic aspect (ie white Muslims are not at risk of higher death rates)

How should the results be interpreted?

These are death rates and reflect the combination both  of how common CoVid is (the ‘incidence’ rate’)  in the different religions and how likely sufferers will die (the ‘case fatality’) in those who contract the virus. 

Is the higher death rate in Jews due to a higher incidence, a higher case fatality (or a mixture of both)?

Of these two possibilities the second is the less likely.  It is known that in the UK, Jewish males have death rates about 40% lower from all causes than the background population with females about 20-30% lower. Thus, British  Jews live longer with, for example, approximately twice as many being over 85 as the background population.  Also, though  not comparing like with like, Israel has one of the highest life expectancies in the world- being similar to Switzerland and Singapore

Thus, the more likely conclusion must be that there is (or was) a higher incidence of CoVid in Jews, rather than a higher case fatality 

It could be debated as to whether this was due to (i) being more likely to be exposed to the virus because of increased likelihood of social contact with an infected individual, and/or (ii) once exposed being more likely to get an actual infection with the same level of contacts.  Theoretically the latter is possible: ie  that Jews are less likely to remain asymptomatic for example are less likely to have pre-existing immunity. There are no data on this.

But one intriguing unanswered question!

In all the analyses on deaths, Jewish males have twice the age adjusted death rate as Jewish females.  That there is an excess death rate from CoVid in UK males  is well described and publicised but the data on Jews are different.  Indeed, Jewish males have around 2.2 times the death rate  of Christian males, whereas Jewish females have only about 1.5 times the death rate of Christian females.  Is it as simple as Jewish men spending more time mixing with each other??  


Can CoVid 19 spread through the air?

Last week 237 scientists from various disciplines signed a letter to a journal suggesting that infection with CoVid 19 could be from airborne transmission and not just by droplets. They called on the World Health Organisation to acknowledge this and advise accordingly.  In this blog I explain what this means and summarise the arguments for and against their suggestion.   I then consider what are the practical consequences if these scientists are right.  

What is the difference between droplet and airborne transmission?

In simple terms, we breathe out drops of different sizes.  When we cough, or sneeze, (even talk loudly or sing!) we breathe out large droplets.  These  can land on surfaces, or if we are close enough land on someone’s eyes, nose or mouths.  If these droplets carry the virus then this can lead to infection.  Because droplets can only travel for a short distance, by keeping a safe distance, thought to be around 2 metres, and especially washing hands in case they have touched surfaces on which there are active droplets, most carriage of infection could be stopped.  Indeed, that was the advice at the beginning of the pandemic.  In general, this has also been the advice for years to avoid catching infections such as flu.

The scientific question is  based on the fact that even when we breathe out normally, we breathe out smaller droplets that hang around in the air for longer times and longer distances.  These smaller droplets are referred to as aerosols (like the air freshener sprays we use at home).  The scientists who signed the letter suggested it is possible that the CoVid virus can also spread in these smaller drops and hence be able to lead to infection at larger distances than 2 metres.  This is illustrated below:  Source: (

There are some key questions:

1. If someone is carrying the virus can they spread the virus via aerosols as well as by droplets?

There is only limited research on this and the data have not been subject to peer review (ie the quality of the research judged by experts to assess its quality). In one research study, Chinese scientists studied the breath of patients with CoVid 19 and looked for evidence of the virus in air samples as well as in their actually exhaled breath. What they found was that there were viral traces in 17% of samples of directly exhaled air (ie the ‘large drops’ in the picture above) but also in 4% of samples of ‘wider’ air (the ‘small drops’). This was a small study but the conclusion was there are traces of the virus in the air from the breaths of people with CoVid

2. Does this type of study prove that the exhaled air contains active virus?

This is a source of dispute between scientists. The studies such as the one above only show that there is viral genetic material (RNA) and cannot prove the actual presence of the ‘whole’ virus. RNA for example may be found in swabs of people who are recovering from infection but that does not mean they are infectious. The problem is that whilst it is easy to investigate for the presence of RNA, it is very difficult to prove the presence of the whole virus.

3. How far can the aerosols spread?

Forgetting CoVid for the moment, there is a general question which is how far aerosols can spread, and the short answer is we don’t know. and depends on so many factors including how they were produced ranging from normal breathing to speaking, sneezing and coughing. Droplet size is also important: larger droplets will fall to the ground closer to the person than smaller droplets. Droplets in aerosols can certainly travel more than 2 metres before dropping

4. How long would the virus last for in the aerosol?

The next question is in a person who has CoVid and is breathing out small droplets in an aerosol how long would a virus survive? This depends on where you are. In laboratory studies, 90% of viruses cannot survive more than 6 minutes outside in sunlight. Contrast that with being inside a poorly ventilated room with no UV light, and the virus within aerosol drops could survive for two hours

5. Would you receive  a big enough dose of the virus to actually get infected?

Thus far much of the above evidence is circumstantial. It is known that we produce aerosols when we breath out normally, and that virus traces can be found in exhaled breath. What is not known is how much virus is needed to trigger an infection. To give an idea of magnitude, a droplet of one ml can contain millions of virus particles and one minute of loud speech could generate 1000 virus-containing droplets, which can remain airborne for 8 minutes. There is also the concern that unlike even other coronaviruses eg SARS, in the laboratory aerosols with CoVid19 can remain infectious for 6 hours. It is important to remember that studying laboratory-based aerosols may not replicate what happens in real life

6. Is there any real life evidence that aerosols can cause CoVid at a greater safe distance than we were led to believe?

At the moment it is anecdotal and based on records of cases occurring in people who were in contact but not close contact. There was an interesting study of people who caught the infection in a restaurant. They proposed that those who did, and who did not, contract the infection could be explained by air conditioning flows rather than their proximity to each other. A now infamous choir practice in Seattle emerged with 52 members being infected. Although it is possible that one affected member spread the virus to all the others by direct droplet, an alternative view is that this person was exhaling aerosols throughout the evening and the high concentration of virus in the exhaled air lead to the high rate of infections

This all sounds quite scary how worried should we be?

Obviously more people would be exposed to the aerosol from an infected person than to their large droplets. Further, even before lockdown measures, an infected person typically spread the virus to less than 3 others (that is, the  R value was under 3).  Given how many people we are in contact with, if aerosol exposure was important then we might have expected a much higher transmission rate. 

In addition, the risk of infection, even by airborne route, depends on the prevalence  of the infection in the population.  As the number of new cases is decreasing, so does the likelihood of coming into contact with someone who is carrying the virus. 

What are the conclusions:

Like so much else with this pandemic despite our desire for hard facts there is much we don’t know.

  1. My conclusion is that whilst the large majority of infections occur from our contact with large droplets, the scientists are right to be cautious in not excluding the theoretical risk of aerosol transmission, even from normal activities in an asymptomatic person.
  2. Statistically the chance of becoming infected in this way is small, and especially small in areas where there have been no recent cases
  3. Outside and in well ventilated spaces and especially where there is UV light, social distancing should offer the necessary level of protection.
  4. SAGE’s advice that when indoors, especially in poorly ventilated places, people should wear face masks, avoid face to face interactions, and loud talking or singing seems sensible  

Interested in further reading:

“Mounting evidence suggests coronavirus is airborne-but health advice has not caught up”.  Nature, 8 July 2020

“How coronavirus spreads through the air: what we know so far” Scientific American, 12 May 2020



Trying to answer friends’ questions!

From the beginning of the Covid epidemic we have been inundated with data and there has never been so much air time or column inches given over to epidemiologists! Yet friends have been confused trying to make sense of it all both for individuals and understanding what’s going on.