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COVID-19: Contact tracing

COVID-19: will contact tracing work?

It’s widely said that testing and contact tracing (using a smartphone app) is the key to the control of COVID-19. But it is not necessarily that simple; there are several unknowns that are worth thinking about.

The textbook example that underpins much of the thinking about this issue is the eradication of smallpox. The later stages of that campaign relied on the early detection of cases and the vaccination of “contacts” (in this case, everyone within a certain area). There are several factors underlying the success of that strategy.

The most obvious is the availability of an effective vaccine. We don’t have that (yet?) for COVID-19.

Secondly, the symptoms of smallpox were obvious and distinctive. There was no need for a complex and time-consuming test to identify a case. In the final stage, in remote areas of Ethiopia, one person in each village was trained to spot, and report, cases, so the vaccination team could respond quickly.

A third important factor is that smallpox is not infective until symptoms appear. Here there is considerable uncertainty in the comparison with COVID-19. There is circumstantial evidence that transmission may occur from pre-symptomatic individuals (i.e., those who subsequently develop symptoms) and possibly also from asymptomatic people (who never develop recognisable symptoms) – although probably to a lesser extent than from those who have symptoms. But we don’t really know, and if it happens to a significant extent it could reduce the effectiveness of a contact tracing strategy. On the other hand, if R is less than one for pre-symptomatic/asymptomatic individuals, then it might not matter.

The comparison with smallpox does have one favourable factor. Both diseases have a relatively low R0 value (2-4)*. This is a marked contrast with another textbook example – measles, where the R0 value is much higher (15-20 is often quoted). Measles also provides another contrast, in that the initial disease is an inconspicuous respiratory tract infection. This is the infectious stage. The typical symptoms come later (they are an immunological response to the virus), and by that stage the patient is not infectious. The high R0 value would make a contact tracing strategy extremely difficult; infectivity before detection makes it effectively impossible.

*A digression to clear up a point that often causes confusion. For epidemics in general, R0 (the basic reproduction rate) is the value of R at the start of a new epidemic, when everyone is susceptible. As the epidemic progresses, and the number who have had the disease (and become immune) increases, the value of R (the actual reproduction rate) declines. For COVID-19, we are largely looking at the effect of control measures rather than the number of those who have become immune; nevertheless it is simpler to refer to this as an effect on R rather than R0.

Before getting back to the point – will contact tracing work in enabling a relaxation of the lockdown while still keeping R below 1? – we need a more subtle interpretation of R. It is an average value across the whole population. If R is very low for some people and much higher for others, you could still get an average value of R <1 even if there is a subpopulation that is spreading the virus quite effectively. If this is geographical (a rural-urban distinction for example) it will show up quite readily (and already does). But if it applies to different groups within say a major city, it is not so easy to see.

Furthermore, although a value of R<1 is (rightly) regarded as a significant point in predicting a decline in the epidemic, it is not an absolute objective. The further it can be reduced, the quicker the epidemic will die out (as well as countering the possibility of a sub-population of spreaders.

Now we can think more clearly about contact tracing. Firstly it depends on the relationship between infectivity and symptoms. Assuming, for the moment, we will not be undertaking massive random testing of the whole population, the contact tracing app will largely apply only to those who are symptomatic. We would have to hope that for those without symptoms, R is already quite low – i.e., there may be a possibility of transmission, but at a low frequency.

Secondly, there is the time factor. Once someone develops symptoms, how soon would they become aware of that and report it? One day? Two days? Then the app needs to notify the identified contacts, who are expected to self-isolate. The crucial factor here is whether those contacts will self-isolate quickly enough, before any of them have become infectious. If the original person is infectious for two days before reporting it, and if the identified contacts don’t act quickly, they may well have been infectious themselves for a day or so before they self-isolate.

The third factor is the degree of uptake of the app. The government originally predicted 80% but have backtracked on that to a figure of 50%. Many people regard that as optimistic – some predictions put it as low as 20%. (Bear in mind that only 79% of adults have a smartphone; for those over 65, it is 40%). Concerns over privacy could have a major impact – I can think of several examples of people who wouldn’t want to disclose who they have been in contact with, however much they are told the data is anonymised!

Then we come to the question of numbers. Suppose we have 10,000 cases per day. (Yesterday, 6 May, there were just over 6k positive tests in the UK, from 57,000 people tested, so the actual number of cases is probably much higher than this). And suppose each case had 5 contacts. That makes 50,000 people per day told to self-isolate for a week – giving a total of 350,000 people self-isolating at any one time. The vast majority will not develop symptoms and may regard the exercise as a waste of time. Is this sustainable?

Of course, if distancing works, there shouldn’t be any contacts, but a lot depends on what the app considers as a ‘contact’. How close do you have to be, and for how long?

You may notice that I’ve said very little about testing. Despite all the publicity about the number of tests being done, and how important it is to do much more, it is far from clear how this would contribute towards a contact tracing strategy. If the identified contacts were tested, would this discriminate between those who had been infected and those who hadn’t? If it did, you could release some from isolation. But there is some doubt as to how early in infection the test result becomes positive, and with the current delays in getting the result back to the subject, they would be half-way through their isolation before they were told the result.

Or, if we did random testing of the population, that would identify a lot of people who were infected but asymptomatic. They could be told to self-isolate, and report it to the app, resulting in a large increase in the number of contacts who would in turn need to self-isolate. But if someone who is asymptomatic transmits the disease only occasionally, this does not have much of an effect.

It would be nice if those advocating a large increase in testing would be more explicit about why it is important. I should emphasise that I’m thinking in terms of control strategy in the general population, and not staff and patients in hospitals and care homes, and similar situations, which is a very different matter, and the need for testing there is quite clear.

The final assessment is that potentially it could work, but it will require a very effective publicity campaign, first to convince people to use the app, and then to take notice of the requirement to self-isolate if they have had a reported contact.

 

COVID-19 vaccines

COVID-19 vaccines

There is no doubt that an effective vaccine against COVID-19 would be a game-changer. So it is not surprising that there are over 100 different vaccine candidates at various stages of development. It might be helpful if I review some of the ways in which vaccines can be developed, starting with the approaches that have been used historically. Whatever approach is used, the goal is to produce a protective immune response, without causing any harm to the subject.

1. Inactivated vaccine. This is conceptually the simplest approach. You grow the virus in the lab and inactivate it, e.g., by heat or chemical treatment, so that it is incapable of causing disease but is still immunogenic. The Salk polio vaccine (the one given by injection, not the ‘sugar-lump ‘one) is an example. Although conceptually simple, very few of the COVID vaccine teams are using this approach. One possible reason is that it requires the production of large amounts of active virus, which is not easy and very hazardous. It also requires meticulous testing to ensure that it is completely inactivated.

2. Live attenuated virus. This requires the virus to be genetically altered in some way so that it is unable to cause disease, but is still viable (so you can still grow it in the lab). If the virus is fully attenuated, this is a safe approach, but achieving attenuation is time-consuming – although these days, rather than trying a variety of random mutants, you can specifically knock out key genes (if you know enough about the biology of the virus). The other polio vaccine (Sabin vaccine) is an example of this type. Again, there are only a few potential COVID vaccines in this category.

3. Toxoids. The third historic approach, exemplified by tetanus and diphtheria vaccines, is to purify and inactivate the bacterial toxin responsible. This is not relevant here (I include it merely for the sake of completeness).

We then come to approaches that rely on recombinant DNA technology (‘genetic engineering’).

4. Recombinant proteins. This involves cloning one of the viral genes (typically coding for a spike protein), and putting it into a bacterial cell (or some other convenient cell) and getting that cell to make quantities of the protein (or a specific part of the protein). The host cell can be grown in large quantities and the desired protein purified for use as a vaccine. Since there is no actual virus involved, this is safe to produce and use, at least from the point of view of infection. Many of the vaccine candidates are of this type (although there may be differences in the details). Since this approach is already used for some existing vaccines, there are already large-scale production facilities available.

5. Viral vectors. In this approach, instead of expressing the protein in a bacterial cell, the gene is inserted into the genome of a harmless virus, so you use the recombinant virus as the vaccine; when it infects a human cell, the required protein will be produced. There are several well-characterised vectors available, which have been developed (and in some cases used) either for other vaccines or for gene therapy. Several of the candidate vaccines that have started clinical trials are of this type.

6. Nucleic acid vaccines. Here the vaccine consists, essentially, of just the RNA of the virus (or a DNA copy of it). The RNA or DNA is taken up by a human cell which uses the information to produce the relevant viral protein. There are also several candidate vaccines of this type in early stage clinical trials.

Testing your vaccine.

The obvious questions are Is it safe? and Does it work?

Ideally, you would start with several different lab animals to see if it is safe to use. You could test the immune response created, but that does not necessarily mean the same thing as efficacy, unless you have an animal model that mimics the human disease, so you can do challenge studies – i.e., you deliberately infect a group of vaccinated animals and see if they survive. You obviously cannot do that with humans!

You would then move, cautiously, to human studies, starting with a very limited number of healthy young volunteers (phase I), mainly to assess any possible side-effects. Again, you can monitor antibody production but you cannot assume that this equates to protection.

Phase II would consist of an extension to a larger panel of subjects, representative of the population, still mainly concerned with safety, but also possibly investigating other factors such as size of dose and route of administration.

Only in phase III would you start in earnest to get data about efficacy. This involves a much larger group of people (often thousands) in a randomised, controlled, double-blind study. They are assigned, randomly, to one of two groups. One group gets the vaccine, and the others something else (in one case, a meningitis vaccine is being used for the control group).  The subjects don’t know which group they are in, nor do those administering the vaccine or assessing the results. The key is held by an independent person who monitors the results as you go along, and may call a halt if anything is obviously going wrong, e.g., there are side effects associated with the use of the vaccine. The trial may also be halted prematurely if things are going very well; if the vaccine clearly works, it is unethical to continue giving a placebo to the control group.

That’s, more or less, the text-book description. With the COVID-19 candidate vaccines, short cuts are being used, partly because of the urgency of the situation, and partly because many of the vaccines involve the use of existing tried and tested technology. So while many vaccines are described as being in clinical trials at phase I, in practice these seem to be hybrid phase I/II trials with an element of phase III in them – e.g, using several hundred volunteers in a randomised controlled trial aimed at assessing efficacy as well as safety.

Jeremy Dale

27 April 2020

 

 

 

COVID-19 tests

COVID-19 tests

There has been a lot of talk about tests for COVID-19 (or the virus that causes it,  SARS-CoV-2). The purpose of this piece is to try to clarify the nature of the tests that are usually referred to, and some other possible tests.

In general, most diagnostic tests for an infectious disease fall under the following headings:

1.Tests for the presence of the whole (‘live’) pathogen

2. Tests for the presence of some part of the pathogen. These can be divided into

a) tests for the nucleic acid of the pathogen (RNA in this case).

b) tests for an antigen of the pathogen

3. Tests for antibodies produced by the body in response to the presence of the pathogen.

1. Live pathogen tests.

For most bacterial diseases, this is the ‘gold standard’. Bacterial pathogens can (mostly) be grown easily in the lab, so this is a good way of detecting them.

It is not so easy for viruses. They don’t grow on their own – they have to get into a cell and use that cell to make more copies of the virus. (This makes it very debatable as to whether we consider a virus as ‘alive’; ‘viable’ is a better term). So you need to start with a culture of a human or other mammalian cell line that you can try to infect with the virus. There is a wide variety of such cell lines in common use in virology laboratories.

Viruses are often fussy – they will grow on some cell lines but not on others. Also, you want to be able to see the effect the virus has on the cells – a ‘cytopathic effect’. Fortunately, previous work with the related virus that caused SARS indicated which cell lines were most likely to be successful. So, quite soon after the first samples became available, several laboratories around the world had successfully cultivated SARS-CoV-2.

But this is not suitable as a diagnostic test. It is too slow (it takes several days or more) and needs high levels of containment. However, being able to grow the virus is important for several reasons, including:

– it is the only way of confirming that the virus is viable (and hence presumably infectious), which is necessary for investigating whether someone is shedding infectious virus, or for testing survival in the environment, for example.

– for lab-based testing of the effects of potential antiviral agents

– providing reasonably large amounts of the virus, especially for the development of some types of vaccines (especially those based on inactivated virus).

2. Tests for the presence of part of the virus.

This is the mainstay of current tests, using a technique known as RT-PCR (Reverse transcriptase-polymerase chain reaction). The RT part copies the viral RNA into DNA, and the PCR amplifies the DNA. It works through a series of cycles, each cycle doubling the amount of DNA. So after 10 cycles, you have 1,000 copies, after 20 cycles a million (106) copies, and after 30 cycles 109 copies. This can all be automated, so you put it into the machine which then tells you when you have a detectable product.

A key element in this process is that it requires the binding of specific ‘primers’ – short lengths of nucleic acid derived from the sequence of the DNA copy of the viral RNA. If the right DNA is present, the primers will bind and you get amplification. If it is not there, there’s no binding, and no amplification. So it is not only exquisitely sensitive, it is also highly specific.

You need to know the sequence of the viral RNA before you can do this. This sequence was made available very shortly after the virus was first identified.

It is important to remember that this test only detects the presence of viral RNA, not the whole virus. So a positive test does not necessarily mean that you are still infectious; it depends on how long the RNA remains after the virus has been inactivated by your immune response.

Some pathogens are detected or identified through the presence of other parts of their structure, mainly those that invoke an immune response – i.e., antigens. I have seen references to an ‘antigen test’ for this virus, but these are probably erroneous references to the RT-PCR test (to contrast it to the antibody tests, see below). There seems no point in an antigen test, which would be slower and less sensitive the RT-PCR.

3. Antibody tests.

These are highly controversial.

The principle is that during infection you produce antibodies (immunoglobulins) that are capable of reacting with a viral antigen (such as the proteins that form the ‘spikes’ on the surface of the virus). So you take a blood sample, mix it with a sample of the specific antigen, and the test detects the binding of the antibody to the antigen. So far, so good.

The problems are of two sorts. Firstly, sensitivity. During the early stages of infection, there may be only low levels of antibody. So you may not detect infection at that stage. Later on, after you have recovered, the antibody levels may drop off quite quickly – so it may not be a good test for immunity (see below).

Secondly, specificity. SARS-CoV-2 is closely related to the SARS virus, and (less closely) to a variety of other coronaviruses that cause a proportion of common colds. While it is easy to make the RT-PCR test specific (by choosing suitable primers), it is not so easy to get a highly specific antibody test.

These problems may be overcome in a lab setting, with experienced technicians, and larger samples of blood – and some laboratories are already conducting surveys using antibody tests. But we are not yet at the stage where you could reliably use a ‘pin-prick’ test in your own home.

This leads on to a related point. If a reliable antibody test says you have antibodies to the virus, what does that mean in practical terms? Especially, will you be resistant to further infection? I don’t want to get bogged down in the direct evidence, which is inconclusive – there are anecdotal reports of a second infection in individuals who have converted to RT-PCR negative (but there are other explanations for that), and on the other hand some animal experiments indicate that re-infection does not happen. The question I want to address is whether the detection of antibodies (assuming a reliable test) means you are now resistant to infection. A full answer, based on general concepts with other viruses, would be far too long and complex to be covered here -and I’m not an immunologist, so I’m not equipped to tackle it, but there are a few points worth making.

– With some viruses, you get ‘neutralising antibodies’ – i.e., binding of the antibodies to the virus is by itself enough to prevent the virus infecting cells (this can be detected in the lab). If that does not happen, the body has other ways of disposing of the virus-antibody complexes, including the activity of various cells such as macrophages and T cells. So in that case your resistance to the disease may depend on this cell-mediated immunity rather than, or as well as, the production of antibodies.

– As described above, antibody levels may fall off considerably after you recover from infection. But it’s worth noting that you can be effectively immune even if antibody levels are low – your immune system may ‘remember’ the previous exposure and produce antibodies very quickly in response to further exposure.

– Antibodies can be damaging as well as protective. The classic example is dengue, where a second infection, with a different strain, causes a much more serious disease – a phenomenon known as antibody-dependent enhancement. Although it is thought unlikely that this will happen with SARS-CoV-2, the prospect is enough to make the vaccine developers twitchy.

Jeremy Dale

24 April 2020

Sunbathing and suicide

Sunbathing and suicide

Some comments on lockdown and exit strategies

The purpose here is not to object to the general concept of a ‘lockdown’ It is a valid strategy for containing an infectious disease. But there are some elements of the strategy that are worth comment, because it is not clear how they contribute to reducing transmission and/or because they might be counter-productive. We will also, sooner or later, need an exit strategy, and I hope the government is already considering the options.

  1. Exercise in the country.

We have been told that we are allowed to have one form of exercise per day, but it must be close to home. That is fine for those of us who live on the edge of open country, but for those who live in cities it means they are confined to parks and other urban open spaces, which runs the risk of those places becoming crowded, and posing a much greater risk of transmission of the virus than if they took a short car ride into open country. Granted that we do not want large collections of people in popular beauty spots (just close the car parks?), nor is it desirable for people to travel hundreds of miles to get their exercise (although I’m not sure what the problem is there, but I’ll let that go). This looks like a London-based rule, that ignores the fact that in many Northern cities, open countryside is only a short way away.

And now, predictably, we have some parks becoming sufficiently crowded that they are threatened with closure (and in some cases have been closed).

There has also been an element of ‘Eyam in reverse’ on some occasions. (Eyam, in case you don’t know, was the ‘plague village’ in Derbyshire which, when plague arrived there, decided to cut themselves off to prevent the spread of the disease to neighbouring villages.)  The comment from Derbyshire Police that some of the people visiting Curbar Edge came from Sheffield sounds rather like the reverse of Eyam’s action. So does the comment on the News tonight from a resident of the Lake District that visitors coming from Manchester were being selfish in that they might be bringing the virus with them. (But I do think that someone from Manchester has no need to go all that way when there are plenty of opportunities much nearer to home).

  1. Are we allowed to enjoy ourselves?

What is the problem with sunbathing, or having a picnic on a (deserted) beach? Provided of course that you keep your distance from everyone else. Yet we have seen police intervening to stop such activities. This looks like a rule that is designed to stop anyone from looking as though they might actually be enjoying themselves. I’ll come back later to the desirability of having fun.

  1. Do arbitrary and pointless rules matter?

At present, the vast majority of people seem to be going along with the rules (at least up to a point), but will it last? As the ancient proverb says “The tighter you screw the lid down, the sooner the boiler will burst”. (Actually, that’s not an ancient proverb; I just made it up. If anyone knows better, let me know!).

In an authoritarian culture, you would get away with it. But we’re not used to being told what to do in such depth, and if people start to think that the rules are unnecessary, it will be hard, if not impossible, to enforce them. Unfortunately, that might mean the sensible rules would be flouted as well as the pointless ones. This will become increasingly important once the peak of the epidemic has passed.

  1. Downsides of the lockdown.

The financial and social problems are sufficiently obvious that I don’t need to go over them. But there are other effects that are not well enough discussed publicly, mainly those associated with being cooped up all day in a small flat. We are starting to see evidence of an increase in domestic violence, mental illness, and apparently also in the number of suicides. There is not much public data yet, but the effects were predicted, so the small amount of evidence is credible.

A more subtle effect is the increased level of stress and anxiety in the population. Although a certain amount of anxiety is needed to ensure that the rules are kept, stress can also be counter-productive for attempts to control the epidemic. We know that factors like immune deficiency, respiratory problems, diabetes, obesity etc are risk factors for infection, and for the severity of the disease. It is less known that stress also reduces our resistance to infection. The precise mechanism of the interaction is imperfectly understood, but it has been shown in humans and in experimental animals, so it is a real effect.

This brings me back to point 3. If allowing people to have a bit of fun occasionally reduces their stress levels, it would go a long way to countering these negative effects of the lockdown.

So keep safe, but have some fun as well.

  1. An exit strategy.

Once the numbers start to come down in earnest, there will be increasing pressure to know when the brakes are coming off.  It will be essential to get this right. If we relax too soon, the epidemic could start off again. If it is delayed too long, apart from the unnecessary financial effects (both on industry and on the workers), there is the risk that people will start to take matters into their own hands.

Furthermore, it will have to be a staged exit. You can’t suddenly say ‘Tomorrow, we’re all back to normal’. The Glossop Labour Club will need to know in advance when we can start ordering beer, and our suppliers, in turn, will need to know when to start making it. Apply that over the whole country, and you can see that chaos will ensue unless the exit is managed carefully.

Am I being too sanguine in hoping that the government is already producing such a plan?

 

 

 

 

Coronavirus – some information

Coronavirus – some information

A The virus

  • COVID-19 is the name of the disease. The name of the virus is SARS-CoV-2. Not very snappy, but it identifies its relationship to the virus (SARS-CoV) that caused the SARS outbreak in 2002. The virus that caused the MERS outbreak in 2012 (MERS-CoV) was also a coronavirus, although a different type. (see below for more about these diseases).
  • It is a virus, not a bacterium. Therefore antibacterial disinfectants will (probably) not be effective. Alcohol (70%) and hypochlorite (bleach) will kill it.
  • Coronaviruses in general are not uncommon – for example, they are estimated to cause about 10% of colds.
  • The genetic material of coronaviruses is RNA, not DNA. This is significant because RNA genomes tend to mutate more rapidly.
  • The RNA is contained in an envelope, which is surrounded by an array of spikes. These are glycoproteins (proteins with sugar molecules attached). The spikes are necessary for attachment to human cells, by binding to specific receptors. The spikes are the likely target for an immune response,
  • After attachment of the virus, the RNA enters the host cell and uses the protein synthesis machinery of the cell to produce the proteins needed for copying the RNA and formation of new virus particles.
  • The cell then dies and releases the new virus particles which go on to infect other cells.

B. COVID-19 and other coronavirus diseases

  • When you cough or sneeze, or, to a lesser extent, speak or just breathe, you shed droplets of various sizes. If you are infected, these will contain virus particles, depending on their size. Bigger droplets are more likely to contain virus.
  • The larger droplets will fall quite quickly (and may contaminate surfaces); smaller ones may remain airborne for some time. These droplets are mainly water. Because of the large surface-volume ratio, the water evaporates readily, forming tiny ‘droplet nuclei’ which can consist of a virus particle and not much else. They may remain airborne for a long time.
  • Incidentally, those droplet nuclei are too small to be intercepted by a mask, so even a well-fitting mask will offer imperfect protection against infection. However, the particles emitted by an infected person are larger, and can be intercepted by a mask. So wearing a mask will reduce the infectivity of someone with the disease.
  • For most respiratory pathogens, it is these droplet nuclei that are the problem, as they are small enough to bypass the mechanical barriers in the respiratory tract and penetrate right into the lungs. SARS-CoV-2 seems to be unusual in that picking it up from contaminated surfaces seems to be more common, and also in that it can infect through the eyes. Hence the advice to decontaminate surfaces and wash your hands frequently
  • The vast majority of infected people show few if any symptoms. This may be due to a level of non-specific immunity to coronaviruses, from previous infections with other coronaviruses, and/or the body’s natural resistance to infection.
  • A small proportion develop severe disease, and some die. In part this it thought to be due to an over-reaction by the immune system. Most of those who die have some underlying health condition, including reduced immunity and pre-existing respiratory tract conditions.
  • There is uncertainty about the real mortality rate (primarily because of uncertainty about the actual number of infections), but the general consensus is that it is about 1%. The mortality rate increases with age, from 50 onwards. This could be due not to age itself but the higher prevalence of underlying conditions, especially the reduction in immunity as you get older.
  • SARS (Severe Acute Respiratory Disease) started in China in 2002. There were over 8000 cases, mainly in China and Hong Kong, plus a number in other countries in the region (e.g., Taiwan, Singapore, Vietnam.) Apart from an outbreak in Canada (257 cases, traced to a traveller from Hong Kong), there was only a sprinkling of cases in the rest of the world. The apparent mortality was quite high (about 10%).
  • MERS (Middle East Respiratory Syndrome). The first case was identified in Saudi Arabia in 2012. Most subsequent cases were in Saudi Arabia, plus smaller numbers in other middle-Eastern countries. There were few cases elsewhere in the world. The disease has reappeared repeatedly in Saudi Arabia, and there was an outbreak in South Korea in 2015 (traced to a man who had visited Saudi Arabia). MERS appears to be more severe, with mortality rates estimated as high as 40%.
  • Why have SARS and MERS (in contrast to COVID-19) not spread more widely? That is a very interesting question, and I wish I knew the answer!

C. Testing

  • The commonly used test is a molecular one technically known as RT-PCR (Reverse Transcriptase- Polymerase Chain Reaction). This copies the RNA into DNA and then amplifies it to an extent that it can be detected. It is very sensitive, but it detects the RNA and not the whole virus. So you may remain positive for a short while after the virus has been eliminated, and you are therefore no longer infectious. Conversely, it may not pick up the infection in the very early stages, when only a few cells are infected.
  • This test requires sophisticated materials and equipment, and skilled technicians. All of these are in short supply, which limits the number that can be done. Some countries were better prepared than others and/or were quicker to react and get everything in place.
  • How important is testing? It is useful for essential staff (esp NHS workers) to know whether or not they are infected, so they can continue to work. Widespread testing would be useful, as getting a better handle on the actual number of cases would inform policy decisions, but I’m sceptical as to how important this is. The traditional view, that finding cases enables the identification of contacts who can then be quarantined, becomes untenable with large number of cases, at least without a degree of surveillance that might well be unacceptable except under authoritarian rule.
  • A different test, that relies on the detection of specific antibodies, is much discussed. Such tests are being evaluated. However, they tell you whether someone has had the disease, not whether they are infected.

D. Interpreting the data

  • We are showered with statistics – numbers of cases or deaths, in various countries. These are a few points to consider when we look at those numbers, especially when comparing data from different countries.
  • Are the numbers adjusted for the population size? Very often they are not, or they don’t say one way or the other. Clearly, a large country would expect more cases than a small one.
  • Do they refer to the cumulative number (the total number of cases/deaths during the epidemic) or the number that day/week?
  • If considering the number of cases, the definition of a ‘case’ may vary between countries. In particular, consider the impact of testing. A country like Germany (which is doing a lot of testing) will identify a large number of cases with few if any symptoms that may not be counted by other countries – and hence will be expected to have a large number of ‘cases’.
  • The number of deaths is often regarded as a more reliable comparison, but this may also have problems. Does it include those who die outside hospital? And remember that many who die as a result (probably) of coronavirus infection actually die from e.g., pneumonia, heart failure, multiple organ failure, etc. How are these deaths recorded? Procedures may vary between countries.
  • To overcome these difficulties, it is best to look at the trends in different countries, i.e., the number of cases/deaths over time. This assumes that the practice in each country is consistent, which is not always true – the UK figure of deaths suddenly jumped today (3 April) after a change in reporting procedure.
  • Bear in mind that there is a delay between ‘cases’ and ‘deaths’ – so you might expect the death rate to continue to go up while the infection rate is levelling off.
  • The trend line will also show where the countries are on the epidemic curve. Italy for example had its first case earlier than Germany did, so comparing those two countries needs to take account of that, in effect looking at where Italy was a short while ago.
  • When considering deaths, it is important to remember that many deaths are among the very old or those who have other serious conditions. Trying not to be callous about this, we have to remember that some of them would be expected to die anyway in any given period. To get a true picture of the impact, we should look at excess deaths – i.e., the number of deaths above the number that would be expected to happen anyway. Bear in mind that there are normally about 0.5 million deaths per year (England and Wales).

E. In defence of ‘herd immunity’

  • The course of an epidemic is determined by a parameter known as R, the Reproduction Number, which is the number of people infected by a single case. At the outset, for COVID-19, R has been estimated as about 2.5.
  • R itself depends on a number of factors; I’ll just consider two of them. Firstly, the number of contacts a person has while they are infectious, and secondly how likely it is that those contacts are actually susceptible to the virus.
  • ‘Social distancing’ (or in extreme cases, isolation) is obviously a way of reducing the first of these.
  • The second factor comes into play when a significant number of people have had the disease (and are, we hope, immune to re-infection). This is the natural way in which an epidemic becomes self-limiting. As more people become infected, and hence immune, R falls. When it gets down to less than 1, the epidemic stops, even though there are a number (possibly a large number) of people still susceptible. This is ‘herd immunity’.
  • The point at which herd immunity kicks in (the Herd Immunity Threshold or HIT) is related to the initial value of R (Ro). Mathematically, the proportion still susceptible at the HIT is 1/Ro. So, if Ro is 2.5, we would get herd immunity with 40% still sensitive, or 60% having been infected. That’s a lot of people. But if we combine it with other measures, effectively reducing the value of Ro, say to 1.5, we get herd immunity after 33% have been infected. And if we reduce Ro still further, to 1, then we get herd immunity straightaway.
  • This is all a gross simplification! In particular, it assumes a homogeneous population, which is obviously not true. Someone living in London, especially if they still travel on public transport, will pass on the virus much more often than someone in the Highlands of Scotland. But it demonstrates the principle.

I hope this all makes sense. If you want to ask anything, or disagree with me, feel free to email me. You might also like to read my book Understanding Microbes which amplifies some of the basic issues (although not COVID-19 as it was published in 2013)

Coronavirus – has the Emperor got any clothes?

It seems to be universally agreed, by journalists, politicians, scientists and everyone else, that China, and potentially the rest of the world, is in the grip of a devastating infectious disease epidemic. I have seen no comments questioning this. But there are questions that should be asked.

1. Is this a new disease? Although this virus is a new one, at least as a cause of human disease, coronaviruses as a group are very common, causing perhaps 10% of common colds, and most people have been infected with one or more of them at some time. But as this is a previously unidentified form of coronavirus, we are justified in regarding it as a new disease.

2. How infectious is it? One estimate that I have seen put its ‘reproductive number’ at 3. That is, each case would infect three other people. While that is plenty for the establishment of an epidemic, it is well short of that seen in a number of other infectious diseases – for example the corresponding number for measles is estimated at 15-20. (That is admittedly an extreme example; estimates for most common infectious diseases lie in the range 2-7).

So it is infectious, but not wildly so – which calls into question the need for the extreme measures being adopted.

Face masks are one form of protection widely used Are they needed? Are they any use? Answering this question needs an understanding of how such infections spread. An infected person will liberate droplets carrying the virus – not just when coughing or sneezing, but when talking or even just breathing normally. Most of those droplets can be trapped by a face mask, as they are relatively large. But they are mainly water, which will evaporate rapidly in the air, leaving tiny particles (known as ‘droplet nuclei’). These carry the virus, and it is this form that is breathed in by others who thus become infected. But these droplet nuclei are too small to be trapped by a simple face mask. So a face mask will cut down the extent to which an infected person will pass on the disease, but offer virtually no protection against becoming infected. (There are also other limitations to a simple face mask, but one will do.)

3. How dangerous is it? While there have been a large number of deaths in China, that needs to be related to the number of cases. That is done by dividing the number of deaths by the number of cases (giving the ‘mortality rate’). The reports from China indicate a mortality rate of between 2 and 3%. That needs to be qualified. While we can be reasonably confident of the number of deaths, we are much less sure of the real number of cases. When a new disease occurs, and/or when there is pressure on resources, it is inevitable that the necessary tests are more likely to be done on subjects with serious disease. Those with a milder disease – and even more so those with no recognisable symptoms – are less likely to be investigated. If we include these subclinical cases, the number infected will be higher, and hence the actual mortality rate will be lower than this estimate. It is repeatedly seen, when a new disease emerges, that initial estimates of mortality are very high, but then drop substantially as more of the less severe cases come to light.

Even if we accept a level of 3%, this does not make it the ‘deadly virus’ that has been reported. This is similar to the mortality rate of a typical outbreak of influenza.

4. Are the resources being devoted to this disease justified?  The world is still suffering from many other infectious diseases, with many more deaths than those caused by this coronavirus. These diseases could be controlled or even eliminated if sufficient resources were available – cholera, malaria, tuberculosis for starters. If a fraction of the resources being poured into controlling this epidemic were applied to, for example, providing clean water and proper sanitation across the planet, we would eliminate cholera (and other water-borne diseases).

5. Why are these questions not being asked?  That brings me back to the title of this blog.

The Emperor’s New Clothes  is a short tale written by Hans Christian Andersen, about two weavers who promise an emperor a new suit of clothes that they say is invisible to those who are unfit for their positions, stupid, or incompetent – while in reality, they make no clothes at all, making everyone believe the clothes are invisible to them. When the emperor parades before his subjects in his new “clothes”, no one dares to say that they do not see any suit of clothes on him for fear that they will be seen as stupid. Finally a child cries out, ‘But he isn’t wearing anything at all!’” (Wikipedia).

No further comment necessary!

Why Labour lost

Various reasons have been put forward as to why Labour lost the recent General Election. Let’s look at some of them.

1. The Labour Party has moved too far to the left. Actually, the policies put forward in the manifesto were far from being extremist. Many of them reflect the current situation in some other European countries, and have also been shown in opinion polls to attract public support. It is a measure of how far the country has moved to the right that such a manifesto could be labelled as extremist. The problem was that the Labour Party never succeeded in shifting the debate onto such policies.

2. The Labour Party has been taken over by metropolitan elites and has lost touch with its core voters. Ever since I’ve been involved in politics (dating back to the 1960s) the Party has been a coalition of people with different backgrounds, and different perspectives – and it remains so. I doubt if an analysis of Jeremy Corbyn’s shadow cabinet would show a significant difference in class background from those of Attlee, Wilson or Blair. But there is some truth in the second part of the above statement. It was apparent in 2017, and even more so in 2019, that the Party has lost a considerable amount of previously automatic support in a number of constituencies.  Despite what many pundits are saying, this is not a recent phenomenon. Taking one constituency, Hartlepool,  the Labour vote varied between 22,000 and 27,000 in every election from 1974 to 2001. Then it went down to 18,251 in 2001 (Tony Blair’s 3rd victory) and again to 16,267 in 2010 and to 14,076 in 2015  Then it bucked the trend, going up to 21,969 in 2017 (under Jeremy Corbyn). In 2019 it was back down, to 15,464,  but this was still higher than achieved in 2015. Nevertheless, it is still far behind the vote achieved in the elections from 1974 to 2001, lending some support to the concept of ‘losing touch with the core voters’, even if that dates back to 2001 rather than recently. In my opinion, this is largely a consequence of the Thatcherite policies of dismantling heavy industry (shipbuilding, steel, coal etc) coupled with the emasculation of the Trade Unions. This has destroyed the social cohesion of these areas. This matters because previously, through those links, the workers in those areas were exposed to a variety of opinions, and discussions, that helped to counter the right-wing propaganda they were fed through the media. So Labour has lost touch with those communities, not through any actions by the Party, but through other factors that the Labour Party has failed to counter. In this context, it can be said that a major failure of the Blair administration was that they did nothing to reverse Thatcher’s anti-Trade Union legislation. In addition, I remember, when I first joined the Party, back in the 1960s, that there were a number of very able people who had missed out on formal education for various reasons, and had worked their way up through the Trades Unions, coupled often with self-education. I suspect that this is less common now, partly because of better educational opportunities (including the expansion of the Universities) – which is obviously a good thing – but also because there are fewer opportunities for ‘working-class’ people to rise through involvement through the Trade Union movement.

3. Brexit.  It is undeniable that a large slice of the population was (is) completely fed up with the Brexit issue and wanted it to go away. Hence the success of the ‘Get Brexit done’ slogan. Labour thought that the debate could be shifted onto other issues, but this proved to be impossible. The policy that they (eventually) went into the election with made sense, theoretically, but was open to the criticism that it would prolong the acrimonious debate – which proved crucial. Labour was too ‘nice’ to point out that it was Johnson and his cronies who were responsible for dragging it out so long.

4. Corbyn. JC was subjected to a continuous barrage of abuse and misinformation, which undoubtedly struck home with some electors. Unfortunately, some of this came from Labour MPs and others who claim to be on the same side. It is very difficult to fight an effective campaign when you are repeatedly stabbed in the back by your own side. This factor was present in 2017 as well, but was to some extent countered by the excitement of having someone new who, when they saw him on the television, came over as fresh and different, and not the ogre he was painted out to be. In 2019. JC’s TV performance seemed, to me, to lack that degree of freshness and excitement; he seemed much too cautious.  However, it has to be said that he leaves the Party in a much better shape than it was. In this constituency (High Peak) membership has soared, and very many of the new members were out on the streets campaigning – which has helped a lot in sealing any initial differences between the new members and the ‘old guard’ – one of whom commented to me that it was great to have a team of people to help him when he previously had to do it all on his own.

5. Where do we go from here? It would be a serious mistake to shift away from a radical agenda to something more ‘centrist’. Although it is of course important to gain power, it is essential to do something with that power, otherwise it is pointless. And the aim should be to achieve changes that are essentially irreversible. The Attlee administration achieved this with the establishment of the NHS (the Tories are still only nibbling at the edges), although many of their other changes were subsequently reversed., as were most of the radical measures of the Wilson years.  The Blair governments (for all their faults) did achieve that with the Nation Minimum wage. But for an extensive and long-lasting shift in the power balance in the UK we have to look at the Thatcher years – de-industrialisation, sale of Council houses, anti-Trade Union legislation – all of these changed the nature of British society in a way that we are still struggling to cope with. So I hope that Jeremy Corbyn’s successor will be elected in a comradely manner, and that s/he will carry on the good work of developing a radical, socialist agenda – and that the Parliamentary Labour Party (and other major figures in the Labour movement) will pull together to re-establish Labour as a dominant force in the country.

Changing cheque signatories

How to change cheque signatories (or not) – a diary

Back in May, I became Treasurer of the Glossop Labour Club. There were other changes to the Committee as well, so we needed to add 3 new signatories to our bank account (and take off 3 as well). No problem, I thought; just pop into the bank and get a form. But it wasn’t that easy. They told me it was all done electronically now, so I had to ring their Business Team to get an electronic form.

21 May. I rang them, and they sent me an email with a PDF attached, into which we had to insert signatures (as a jpg), and attach PDF copies of photo ID (passport or driving licence) and proof of address. Taking a photo of my signature was a pain, but eventually I got something I thought was OK.  I then needed to pass it on to the others to do the same. But neither of them could get the form to work. So they passed all the details to me and I finished filling in the forms. That all took about a month.

I also got them to send me a form to apply for online banking, which was simpler – just print it out and fill it in, then return it by post, which I did on 19 June.

28 June.  What do I do with the signature forms now? There was a button marked Submit. But all that did was create a gmail account that I didn’t want. So I rang them again. “Oh” they said, sounding surprised. “Well, then email it to us.” “But you haven’t given an email address.” So they gave me one, and I emailed it to them.

At the same time, I asked about the online banking form. It had been received, but they couldn’t process it because I wasn’t a recognised signatory.

9 July. As I hadn’t heard anything, I rang them again. “You sent an e-mail? We get so many e-mails we don’t bother to read them. You had better print it off and post it.”

16 July. Still no news, so I rang them again. “We received it yesterday. Ring again in a week’s time,” (Their website says it usually takes a few days).

24 July. “We’re still working on it, Ring again next week.”

30 July. One of the signatures is unclear. So I did some electronic enhancement on it, and sent it back by post.

7 August. We received a letter saying the other two signatures are unclear. They provided a piece of paper for us to sign and return by post, which we did.

9 September. No news, so I asked at the local branch if the new signatories were now OK, which they weren’t. So I rang them again. The problem now was that the Chairman, who signed the form to say that we had passed the appropriate resolutions wasn’t a recognised signatory (he’s one of the ones being added) so he had to go into a bank branch to verify his identity.

3 October. So that’s where we are now. I’ve been Treasurer for coming up to 4 months and I still can’t sign cheques. I wonder if we will get this finished before the next AGM when we might have to start all over again. And online banking is still a dream – that process can’t start until the signatories have been changed. I hope that doesn’t take as long.

An update:

11 October. I rang the Business team: ther’s a bit of a delay. Call back next week.

21 October. The business team have not heard from the local branch about our Chairman’s identification.

November. Our Chairman confirms that he has presented his documentation to the Branch. So I checked with the Branch – they say they have no way of passing the information to the Business Team.

10 December. I rang the Business Team again (Every time I do this, I get a recorded message saying they are having a higher than normal number of calls!). He said that there seem to be no further deficiencies, and he is trying to get ‘them’ to activate it.

17 December. I asked at the Branch, and they said it had not yet been done. So I am still waiting.

Further update, January 2020.

I can’t believ it! It’s been done! I can now sign cheques – after over 7 months trying.

Now to try to get them to allow us online banking.

 

An excellent day !?

I left the house at about 8.20, caught the train into Manchester. So far, so good.

But, just after we left Flowery Field, the train ground to a stop. And stayed there. The very helpful guard explained that there was a problem with the overhead power lines, and we were likely to be there for some time. After about an hour (!), he told us that we would have to do a ‘controlled evacuation’ and walk back to Flowery Field station where a bus would take us into Manchester.

So we did that. But there was no bus. We were told to walk to Hyde North station, which was only a few minutes away, and get another train from there. He didn’t say it was a few minutes by car, and about 15 minutes on foot.

When we eventually got to Hyde North, a train did arrive, but then it sat there to wait for everyone else. We finally got to Piccadilly about 11.30. I decided I had done enough walking and would catch the free bus, but that didn’t turn up for about 15 minutes. Then at the junction with King Street, there was a lorry blocking the road. We sat there for a while and then were told to get off and walk. (Ironically, it was  Kingspan lorry!)

So I eventually arrived about 12.15 – nearly 4 hours for a journey that normally takes about 1.5 hours door to door. I then checked in, and was told that by that time they had sorted out all the jury panels that were needed that day, so I could go home again!

Fortunately the journey home was uneventful and I got back at about 1.45 having spent 5.5 hours achieving nothing (apart from experiencing a controlled evacuation and finding out where Hyde North station is.)

Vaccination

Despite the clear success of vaccination in the control of a number of infectious diseases, there are still far too many people who decline vaccination, for themselves or for their children. Why is this, and why does it matter?

The reasons fo declining vaccination, ignoring inertia, are i) doubts over the effectiveness of vaccines and ii) concerns about safety. The first point is totally unfounded. Smallpox was completely eliminated, in large part due to the success of the vaccine. Polio has been almost eliminated – and could be by now if the few countries where it still exists were not so resistant to use of the vaccine. Diphtheria, tetanus, – the list goes on.  All the vaccines in current use have been shown to be effective (leaving aside the use of BCG for control of TB, which is a complicated question).

That brings us to the safety issue, and especially the MMR (measles, mumps, rubella) vaccine. In 1998, Andrew Wakefield and colleagues published a paper describing a study of 12 children with autism and chronic intestinal disorders. An incidental finding was that most of these children had received MMR. Although the paper actually states that they did not prove an association between autism and MMR, it was widely believed that they had. This erroneous belief still persists, despite numerous large and well-conducted studies that have failed to find any association whatever, and despite the fact that the Wakefield paper has now been withdrawn. To a large extent, the misplaced belief is fuelled by the fact that the age at which the MMR vaccine is given is the age at which signs of autism often first appear – so it is inevitable that in some cases autism will show up soon after the vaccine is administrered.

A very similar situation arose in the 1970s with the whooping cough (pertusssi) vaccine, where some children showed neurological problems after having the vaccine. This wasn’t anything to do with the vaccine – it’s just that some children do have these symptoms at about that age. But the unjustified fear of the vaccine led to a decline in its uptake, with the consequence that in the winter of 1978-79 there wee 100,000 cases in the UK, with many deaths and even more neurological problems.

Finally, does it matter if some people refuse the vaccine? Isn’t it a matter of personal choice, to accept the risk of getting the disease? The answer lies in the question of how can we protect those who cannot be vaccinated – especially very young children who are too young to be immunised (because their immune system is not fully devloped)?

Spread of a disease depends on an infected person coming into contact with others who are susceptible to the disease. If you can reduce the proportion who are susceptible to a low enough level, then the disease will not spread. This is known as herd immunity. For smallpox, it was quite easy – only about 75% needed to be vaccinated to stamp out the disease completely. Measles is much more infectious, and the critical level is much higher – about 95%. Failure to achieve that level means epidemics will occur – and they are occurring. So those people who refuse vaccination are not only putting their own children at risk, but they are putting others at risk, including all those babies who cannot be immunised.

For a more complete coverage, read my book Understanding Microbes