Where’s our herd immunity?

Where’s our herd immunity?

In the early stages of the COVID-19 pandemic, there was a lot of discussion about herd immunity. Once a certain number of people had become immune through being infected, the epidemic would grind to a halt. This level is known as the Herd Immunity Threshold (HIT). There was (and still is) uncertainty as to exactly where this would kick in. Let’s call it 70%.

How many people have been infected? If we just consider those diagnosed, that ignores the asymptomatic cases. If we consider those who have tested positive, that understates the position because the tests weren’t available to start with, and there may still be asymptomatic cases not detected because they have no reason to take  a test. We can start with the number of deaths (as recorded on death certificates – currently about 150k). If the case fatality rate (CFR) is 1%, that translates to 15 million cases. (The CFR is higher in elderly and otherwise highly susceptible, and lower in younger people, but let’s focus on the concept rather than the accuracy of the data.) That’s about 20% of the population.

Of course, those earlier calculations were just based on becoming immune through being infected – but we now have the vaccines to consider. The headline figures that are generally quoted (e.g., BBC TV News) are that 90% of the adult population have had one dose, and about 66% have had both doses. You might think that we could add that to the above 20% who have been infected, but it’s not that simple – the two overlap (i.e., some of the vaccinated people will have had COVID already). Nevertheless, it is clear that the percentages are at or above the HIT. That is supported by surveys carried out by ONS which show that about 90% of UK adults have antibodies to SARS-CoV-2.

The snag here is the word ‘adults’ in the previous paragraph (i.e., those 18 or over). The ONS antibody survey shows that it is effectively 100% in those 50 or over, 95% for 35-49. dropping to 80% for 25-34 years, and only 60% for those in the 16-24 group. They don’t give figures for anyone under 16. (These figures are for England only; the details are different for the other nations, but the trends are the same).

Does this matter? It seems likely that if we consider the impact of vaccination and natural immunity combined, we should be near the HIT for the whole population. To show that it does matter, we have to consider the assumptions behind the concept of herd immunity. The most basic forms of epidemic modelling make two important assumptions: i) that the population is homogeneous, and ii) that it is randomly mixed. In more simple terms, this means that whoever you are, and wherever you are, if you have COVID, the number of people you are likely to infect is the same. This is obviously not true. If you live in a remote part of Scotland, you are less likely to infect others than if you live in central London. (I should add that modern epidemic modelling is much more sophisticated than the simple model, but the basic concept of herd immunity is still affected by these factors).

The most relevant, but somewhat less obvious, limitation here is the assumption of random mixing. Is the population in a specific area randomly mixed? If you have an infected 16 year old, are they more likely to pass it on to another 16 year old or to someone at 76? (I can’t remember the last time I came into close contact with a 16 year old!). So with the younger age groups not fully protected, it is quite possible to have rampant spread of infection there, while the older age groups are well protected.

To some extent, this is borne out by looking at the age group distribution of test positivity rates. Over the last month, these have risen from a very low level to 2-3% (daily) in school year 7 to age 24, and up to 1.4% in age 2 to school year 6, and those between 25 and 34. While there were increases in older age groups, these were much less. (A pinch of salt here – if more tests are done, you might get an apparent increase in the number of positive tests without there being an actual increase in the number of cases – you are just detecting them better).

So the current increase in the number of cases is being driven, to a large extent, by infections in younger age groups, who have not been vaccinated. This highlights the decision that was made in the vaccination campaign – to start with the older age groups and work downwards. Why was this decision taken? If the focus had been on simply controlling the number of cases, it might have been better to go all out for vaccinating everyone – especially as the younger age groups tend to mix more than the elderly do. The reason for starting with the most vulnerable comes down to the effect on the NHS. Older people (and others who are more vulnerable) are more likely to require hospital treatment, and especially intensive care, while those who are younger will often have only relatively mild  symptoms.

If we are to finally get on top of this disease, it is essential that vaccine uptake is increased in the younger age groups (and also in other groups that are at present under-vaccinated: e.g., some towns, some minority ethnic groups). It is disappointing therefore that the rate of vaccination has slowed markedly. In April/May, the total number of vaccinations (first and second doses) was as high as 600,000, Now it is down to not much over 200,000. Of these only 71,000 are first doses – so when they become eligible for a second dose, the number will be correspondingly low.

However, I am optimistic. The number of deaths is still very low compared to previous waves, either because the vaccination is reducing the effects of infection, or the proportion of cases amongst younger people is higher (or both). And if younger people are being infected without becoming seriously ill, that is doing the same job as vaccinating them – increasing the level of immunity. Let’s keep hoping!

Jeremy Dale

16 July 2021

Covid19 – another update

This is a good time to re-examine how well, or how badly, the UK has done, and some of the factors involved.

1. Number of deaths.

Data from https://www.worldometers.info/coronavirus/#countries [accessed 28-3-21]

We are frequently told that USA and Brazil have suffered greatly – and in terms of total deaths (562k, 310k respectively) that is true. But their population is much larger than that of the UK, and that has to be taken into account, by looking at the deaths per 100k population. If we do this for a selection of countries, we see the following table

CountryDeaths per 100k
UK186
Italy178
USA169
Spain160
Brazil145
France145
Germany91

I should add the caveat that the method of counting deaths varies from one country to another (even with the UK figures we get a different number from different sources), so the comparison is not absolutely reliable. It is also worth noting that some of the other countries have been catching up with us – the same comparison a month or two ago would have shown us to be further ‘ahead’. But it is quite clear that we have nothing to be proud of in the way we have dealt with the pandemic.

2. What could we have done better?

i) Lockdown and other controls. Obviously we were very slow to respond at the start; the Government delayed its response inexcusably. Would it have made any difference?

If we cast our minds back to January/February 2020, nobody knew when vaccines would become available, nor even whether effective vaccines would be possible. In the absence of a vaccine, all that can be achieved by lockdown (and other control measures such as border controls), would be a delay in the spread of the virus. It would not reduce the number of cases or deaths ultimately. The only factor that would eventually control the infection (in the absence of a vaccine) would be the much maligned concept of ‘herd immunity’ – eventually the number of people who had been infected (and hence became immune) would reach a level where further spread of the disease stopped. I should make it clear that this does not constitute advocating that as a policy; it is simply stating a fact.

That doesn’t mean that those control measures were pointless. Delaying the spread, or ‘smoothing the curve’, has a value. Spreading out the number of cases over time reduces the risk that hospitals would become overwhelmed. It also buys time for the development of a vaccine – and as it turns out that was critical. If our earlier control measures had been more effective, some of the people who died would now be available for vaccination.

ii) Border controls. Some countries have achieved a remarkable level of success by using border controls, coupled with rigorous lockdown measures. We are often told about New Zealand, Iceland, and Taiwan. for example. NZ and Iceland are much smaller countries, and much more isolated than the UK. Even Taiwan (which was cited as an example in a recent Guardian article) is only 1/3 of the size of the UK, and although it has frequent flights from China, it is more isolated than the UK. Although Britain is also an island, would it really be feasible to cut ourselves off from everywhere else in the way those other countries have done? All those ferries – and the Channel Tunnel – and including all the crews of the ferries, and the lorry drivers. To say nothing of the likelihood of informal passage from the continent. You can easily sail a small boat across the Channel, but I don’t fancy your chances of doing that to Iceland, or Taiwan; you would certainly need to know what you were doing. The experience of the Isle of Man is instructive here – they thought they had it sorted, and re-opened pubs etc. But it couldn’t be maintained, and now they have problems.

In the absence of a vaccine, such a policy would have to be continued until the disease was eliminated throughout the world.

3. We could have been better prepared.

i) General health. Many of the Covid-related deaths have been in ‘high-risk’ groups of people. Of these, I want to single out two factors: obesity and pre-existing respiratory conditions (for which air pollution is a major contributing factor). The Government has prevaricated for years over taking effective action to counter either of these problems. This is a major reason why we have done so badly in the current pandemic.

ii) The health service. The Government has treated the health service as a business, like selling soap. It’s not efficient to keep large reserve stocks of soap. You can predict how much soap people will buy, and if more is needed, you can get more supplies – ‘just in time’. That doesn’t work with the health service. Up to a point, you can predict how much spare capacity will be needed in an average winter, but that falls down when faced with an unexpected demand such a  pandemic. As we found out, it is not easy to suddenly buy in large supplies of PPE or respirators, when other countries are trying to do the same. And worse than that, you cannot suddenly increase the numbers of trained doctors and nurses. So the Government built all those Nightingale hospitals, forgetting that there were not enough staff available to run them – so they have been largely unused.

Several previous exercises had demonstrated that the health service was ill-equipped to deal with a pandemic – but these were ignored.

iii) Test and trace. We used to have a system where most hospitals had their own diagnostic laboratory, backed up by a network of laboratories run by the Public Health Laboratory Service. So samples could be taken locally (either in hospitals or by GPs), and tested locally. Hence people ddn’t have to travel long distances to get a test, and the results were available very quickly (often the same day). If contact tracing was required, that was also done locally, under the auspices of the local authority. That system could have been used to run test and trace, but much of it had been gradually eroded, by merging laboratories (so they are less local), abolishing the PHLS (the remnants being formed into the Health Protection Agency, HPA), and slashing local authority budgets, so the contact tracing teams are now a shadow of their former selves. The Government seemed to decide that was left of the system was not capable of doing the job, so they outsourced it, ending up with a system that was not fit for purpose, and was a gross waste of public funds.

Although I am cross about the waste of money, I’m not sure that it made any difference to the pandemic. Contact tracing is crucial in the control of some infectious diseases – tuberculosis and sexually transmitted diseases being two prime examples. In both cases, these are long-term infections, where the person concerned will go on infecting others for ages, so you not only have an opportunity to prevent further transmission, but you can also do contact tracing backwards – find out where they might have caught the disease, and deal with that as well. These diseases also highlight the value of having a team of trained, experienced contact tracers. It requires a good deal of tact and professionalism to ask someone where they might have contracted a sexually transmitted disease. Plus local knowledge as well. Someone with an hour or two of training, working from a call centre, is not going to get far.

The main problem with contact tracing for Covid comes down to timing. If you consider someone who is infected on day 0, then suppose they become infectious on day 4 (but not yet symptomatic). So they have started spreading it to others. They develop symptoms on, say, day 6. On day 7, they think “I’m ill, I must do something”. So they book a test, which is done on day 8. On day 9 they get the results and are told to isolate. On day 10, the contact tracers have talked to the identified contacts. But those who were infected on day 4 have now been infected for 6 days, and have started to spread it to others. I admit that the timings I have used are guesswork, but the general message holds – it is very difficult to get through the process quickly enough to interrupt transmission effectively.

4. Vaccine

Here, at last, we come to an area where the Government has done some things right. First of all, they seem to have got ahead of the curve in placing advance orders for large quantities of several potential vaccines, at a time when it was still uncertain whether any of them would work. We should also give credit to the UK’s regulator, MHRA, in giving speedy assent (on an emergency basis) to the vaccines. It is rather cheeky of the Government to claim credit for the development of the Oxford/AstraZeneca vaccine; the work of the Oxford Vaccine Group was largely based on blue-skies research in developing their vaccine delivery system.

The Government also made a good decision over vaccine delivery. They decided to keep their hands off! – and especially in not out-sourcing it. They just let the NHS get on with it, with the result that groups of GPs, community organisations, and many others moved very quickly to set up an impressive network of vaccination centres, including taking the vaccination out to the people who needed it.

But what about the variants? Are they going to compromise the success of the vaccines? The first thing to make clear is that variation is nothing new. Almost certainly, the flu pandemics that we have had from time to time will have been influenced by the occurrence of variants of the flu virus – indeed there is some retrospective evidence that this happened. And flu viruses seem to be more variable than coronaviruses. This is largely responsible for the repeated outbreaks of seasonal flu (the flu pandemics are caused by a more radical reshuffling of genes between human and animal strains). What is new about Covid-19 is that for the first time we have been able to follow the emergence of these variants as they happen.

Secondly, there are severe limitations on the extent to which the spike protein can vary. It has to be able to recognise a specific receptor on human cells. If it varies too much, it won’t interact effectively with that receptor and will lose infectivity. So the virus has to tread a narrow line between escaping immunity due to the vaccine (or prior infection) while still retaining infectivity. Furthermore, we cannot assume that a variant that becomes predominant, displacing a previous strain, is inherently more infectious. A variant that causes less severe disease can have an advantage, as those infected will be less ill, and therefore less likely to self-isolate. It has been suggested that the emergence of such a partially attenuated variant was responsible for the ending of the 1918-19 flu pandemic. In addition, our immune system is very complex. Each of us will produce a unique mixture of antibodies in response to the vaccine, or to infection; some of these antibodies will be very specific, and will fail to recognise the new variant, while other antibodies are less specific and will recognise a wide variety of related strains. So some people will be fully protected; others, perhaps less so. That’s one of the reasons why, when we get a bad year for seasonal flu, some get infected while others do not. So, there’s no need to panic – but it is sensible for the vaccine companies to make new versions of their vaccines – which they are doing, as it is relatively straightforward to do (and is already done for flu vaccines as new variants emerge).

5. What of the future?

It is certain that there will be future pandemics. We are better prepared for flu than we were for the pandemics in 1918, or even 1957 or 1968 – not only in the ability to produce new vaccines quickly but also because of the availability of antiviral agents that can be used for treatment of influenza. SARS-CoV2 is likely to remain with us after the current pandemic is over, perhaps producing seasonal outbreaks. We don’t yet have antiviral agents that can be used against coronaviruses, but they will come – there are many candidates being investigated.

But what about further novel pathogens? We have to recognise that in a sense we have been lucky over the last century or two. Influenza and coronaviruses are both only moderately transmissible and moderately pathogenic. After the experience of the last 12 months, that may sound a surprising statement. But an Ro value of 2-4 (for Covid) looks small compared to measles (Ro 15-20). And the case-fatality rate CFR (the chance of dying if you have been infected) of perhaps 1% for Covid is low compared to that for plague or smallpox (about 50%), or HIV/AIDS (where, before the advent of anti-retroviral therapy, it was effectively 100%). If you want a sleepless night, try imagining a pandemic caused by a pathogen with the infectivity of measles and the CFR of HIV.

Jeremy Dale

29/3/21