Category: Immunity

South African and UK: two Covid-19 variants – two countries in crisis ?

Post author By alansilman
Post date 24th Dec 2020
2 Comments on South African and UK: two Covid-19 variants – two countries in crisis ?

The UK and South Africa are two countries where the transmission of the virus has escalated. Last week a highly transmissible new strain was identified as the source in the UK. Three days ago, the explanation of a marked upswing in cases in South Africa was also shown to be related to a new genetic variant of the Covid-19 virus. Indeed, in an unpleasant twist, two cases of this variant were also yesterday reported to the UK. The outbreak caused by these new variants will be much more challenging to control, both within these countries and beyond.

(I hadn’t intended blogging again before the holiday, but these new data are sufficiently concerning I thought readers would want some of this background!)

Some comments on terms!

Mutation – a change in one of the genes of the virus as it multiplies
Variant – as a consequence of one or more mutations, a different version of the virus appears with slightly different genes from the initial version
Strain – often refers to when a particular variant becomes an important cause of some or all of the cases in a particular outbreak

Thus the new UK strain has some 23 separate mutations and this variant has become the dominant strain causing infection in much of this country

What do we know about the new South African strain?

South Africa has seen a marked increase recently in the number of new cases of Covid-19

Around 90% of new cases in that country are due to a new strain, based on a number of mutations
As well as the 2 UK cases, the South African variant has now been found in Australia and Switzerland
No doubt as other countries undertake the necessary complex genetic analysis this strain will also be identified in many other countries

Concern in younger people

At the beginning of the epidemic less than 0.5% of cases in South Africa were in people under 30 (which may be related to who was being tested)
In some South African provinces the peak age is now in the 15-19 year age group

https://www.plenglish.com/index.php?o=rn&id=62600&SEO=south-africa-affected-by-second-wave-of-covid-19

As with the new UK strain, the new South African one multiplies much more quickly than the previous common strains
The problem is that those infected with these strains then produce much larger amounts of virus.
Thus, the concern is young people infected with these strains have higher levels of virus than they did with the previous strain: the latter of which only rarely led to a severe illness.
The greater viral load with the new strain could make them sicker
Indeed, there are a few unconfirmed reports from South Africa, of young people with no pre-existing illnesses who became seriously ill with this strain
It is too early to know how big these numbers are

How close are the South African and UK strains?

Both strains are quite different variants
Both however contain a number of mutations in the spike protein region, thought to be responsible for the increase in transmission
Thus both the South African and the new UK strain carry the same ‘N501Y’ mutation in the spike protein
It is likely that that these two variants have arisen spontaneously in different countries, but by chance both of them are particularly highly transmissible
We may see other countries reporting on other highly transmissible strains

For the UK variant, is there any new analysis of its impact?

In my post last week I thought it was highly likely that the UK strain would result in an increase in R
The graph below, from an epidemiology modelling unit in Oxford shows that the transmission rate, R, is now well over 1.0

http://epidemicforecasting.org/country-rt-estimates?region=GB

It is fairly definite that the increase in R is because of the UK’s new strain (now called B117 or VUI-202012/0)
What is interesting is that South Africa and the UK are two countries which, despite all the current lockdowns and mitigations, have two of the highest estimated R values in the world
- UK R=1.26
- South Africa R=1.33
As a comparison the estimates for other high prevalence countries are lower
- USA R= 1.03
- France R = 1.06
- Italy R = 0.88

Conclusions about these new strains remain the same

New strains occurring during a pandemic are not unusual
The fact that these strains are more likely to transmit infection does not mean that the infection is more serious, but this will need to be monitored
Most experts also still expect the new vaccines to be effective, as the antibodies generated by these vaccines should still ‘work’ against even the mutant forms of the spike protein
As I mentioned last week, if necessary new vaccines can be made very easily against a new strain
Indeed, one sensible suggestion this week was that even if the vaccines turn out to be less effective against any new strain, that wouldn’t necessarily be a big problem
Given what is known about the effectiveness and safety of existing vaccines, it may be possible for regulators to approve slightly modified new vaccines without the need for additional lengthy trials

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Covid-19 Immunity transmission Vaccines

What percent of the population needs to be vaccinated to end the pandemic?

Post author By alansilman
Post date 13th Nov 2020
8 Comments on What percent of the population needs to be vaccinated to end the pandemic?

As I mentioned in my posts this week, a vaccine protects us in two ways: (i) direct benefit from our our vaccination and (ii) by herd immunity – the vaccine protecting enough of the population to put an end to the virus spreading between people. There is a need for any CoVid-19 vaccine programme to produce herd immunity as the vaccine may not work in everyone and its effects may not last. In this post I consider, given our current knowledge about the possible vaccines and the behaviour of the virus, just how easy it will be to induce herd immunity.

(A quick note to say that I have tried to make the answer to a complex question easy to follow, especially for people who are not experts in maths! Feel free to go straight to the conclusions at the end! You might find it easier to read this on an iPad or laptop rather than a mobile to take it all in – but do feedback whether it is too complicated).

A quick refresher on herd immunity!

During an epidemic we can divide the population into 3 groups
- those who are infected (the red figures below)
- those who are susceptible – ie have no immunity to the infection (the light blue figures below)
- those who are immune-ie are protected against infection and therefore cannot pass it on to others (the green figures below)
- (Individuals can be immune either because of natural infection or because of vaccination)
In the picture below, when there has been no vaccination programme, the larger red figure can spread the infection to lots of the susceptible people

https://www.technologynetworks.com/immunology/news/herd-immunity-is-a-dangerous-strategy-for-tackling-covid-19-339142

Now, following a vaccination programme, together with people who have become immune naturally, the situation is as in the picture below
The infected person has far fewer people that they can pass on the infection to. More importantly, the people who are still susceptible are less likely to come in contact with an infected person. In this picture the large red figure can only infect one other person, whilst the light blue figures are surrounded by people who are immune

When transmission of infection effectively stops, we say that there is a state of herd immunity.
As shown in the pictures, we don’t need for everyone to be immune to bring about herd immunity
The proportion who need to be immune varies between viruses. The more infectious a virus, the higher the proportion needs to be

What are the key factors that will determine how many people need to be vaccinated to achieve herd immunity with Covid-19?

A paper in the Lancet* on November 4^th showed that is possible to calculate the answer to this question
The calculations need to consider the following factors:
- What is the rate of transmission?
- The short term efficacy of the vaccine
- How long the vaccine protection will last

These are considered in turn below

*https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32318-7/fulltext

What is the rate of transmission?

This is the ‘R’ we’ve been hearing so much about
We all know that if ‘R’ is below 1.0, then the infection will die out (and theoretically no vaccination is needed)
We can only achieve an ‘R’ of that level with very strict social distancing and other mitigation strategies (eg face masks)
Without any mitigation strategies, the natural ‘R’ for Covid-19 is around 2.5-3.5 (each infected person, on average, infects between 2.5 and 3.5 other people)
In my calculations, I have considered 3 possible scenarios with a vaccination programme
- We continue to adopt mitigation measures such as face masks and social distancing, accepting that the ‘R’ will fall to say 1.2, but won’t get below the magic 1.0
- Once the vaccination programme starts, those who have been vaccinated then go back to normal life, ie the transmission rate is 2.5
- As above, but a more pessimistic R of 3.5
This is what the calculations show:

To explain this graph, the blue bars show the percent of people who need to be vaccinated to achieve herd immunity for different values of R
If R is 1, as explained above, we don’t need a vaccination programme as the infection will disappear in time
If R remains as 1.2, then only around 16% of the population will need to be vaccinated to achieve herd immunity, but that means staying in some kind of lockdown until that has been achieved
If we go back to normal life and R is as high as 3.5 then we would need to vaccinate around 70% of the population to achieve herd immunity (shown approximately by the white arrows)

The short term efficacy of the vaccine

The calculations above assume the vaccine is 100% effective
The Pfizer vaccine data suggested 90% efficacy – that might be optimistic and may not apply to all sub-groups, e.g. those who are elderly
Obviously the lower the efficacy, the lower the proportion who are vaccinated who are actually immune
We also do not know what the efficacy of other vaccines might be, so I have assumed that the range will be from 60% to 100%
I have recalculated the figures from the graph above to allow for differences in the efficacy rate
This is what I found:

Let me help you to follow this graph*
The orange bars could represent Pfizer’s vaccine, with its reported 90% efficacy
The yellow bars could represent another company’s vaccine which may report 70% efficacy
Thus, if we remain in some kind of lockdown, ie with a ‘R’ of around 1.2, then to achieve herd immunity we would need to vaccinate 18.5% with the Pfizer vaccine and 22.8% with the new vaccine (red arrows)
If we resume normal activities and accept an ‘R’ of 3. 5, then we would need to vaccinate 79% with the Pfizer vaccine and 98% with the new vaccine (blue arrows)
Comment: it is highly unlikely that we could achieve anything like a 98% coverage

*It’s a bit confusing as there are two percentages here. The figures above the coloured squares show the percentage efficacy of the vaccine. The numbers on the vertical axis of the graph show the percentage of people that need to be vaccinated

How long the vaccine protection will last?

This will also prove to be a challenge
We don’t know how long the immunity reported in the initial findings of the Pfizer trial, or with any of the vaccines, will last for
This is important as it will influence over how short a time the vaccination programme needs to be delivered. This will then impact on how long herd immunity will last for
If herd immunity begins to be lost, then booster immunization programmes will be needed
The Lancet paper did some fairly complex calculations and from their figures I have produced the following graph based on an assumption of
- A vaccine which is 80% effective
- An R value of 2.5

What this graph shows is that if a vaccine is 90% effective then herd immunity will last for around 17 months. If it is 97.5% effective it will last for over 2 years. If it is only 75% effective it will last just 10 months
Whenever that time point is reached then, as stated above, if the infection is still around a booster may be needed
None of these calculations have considered the fact that over time a new vaccine may be required to cope with a changing strain of the virus
However, the vaccine developers have shown they ae very nimble and should be able to adapt production of any new vaccine to cope

Conclusions

Whether or not the vaccine is effective for any of us as individuals: for our continued protection and for society to return to normal, we need a vaccination programme to deliver herd immunity
The chances of herd immunity are obviously increased the more effective the vaccine. Vaccines with lower than the current reported success for the Pfizer vaccine can achieve herd immunity – but these would need very high take up rates of vaccination
Herd immunity will be easier to achieve if coupled with a continued stringency in adherence to mitigation actions such as mask wearing and social distancing – although this is something of a balancing act, as the aim of a successful vaccination programme is to return to normality

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Anti-viral drugs Immunity Outcome transmission

Genetic mutations in the virus and in humans: Do they offer a way out?

Post author By alansilman
Post date 13th Oct 2020
3 Comments on Genetic mutations in the virus and in humans: Do they offer a way out?

As the pandemic progresses the virus mutates. Mutations in us result in differences in how our immune system fights the infection. In this post I review how recent research on the impacts of these mutations could change the way we control and treat the disease – I found the results really interesting and even hopeful!

What is a mutation?

The different genes in every organism, from virus to man, consist of chains of different sequences of 4 building blocks, called nucleotides
The 4 – referred to as ‘A’, ‘C’ ‘G’ and ‘T’- can form very long sequences with up to 2 million in any one gene
You can think of genes as very long necklaces made up of Lego blocks in the 4 main colours

The exact sequence of the nucleotides in each individual gene does vary:
- no two humans have identical sequences in any of our genes: there are many points of difference
- even though a virus has far fewer and much shorter genes, there can be many differences in the genes (these are then referred to as different ‘strains’)
Such differences in the sequence of nucleotides are referred to as mutations. Mutations continually occur in all species
In some mutations, there is a substitution of one nucleotide for another
- In the example below a ‘red’ T was substituted by a ‘blue’ ‘C’

source: http://biology4alevel.blogspot.com/2016/06/133-genetic-mutations.html

In other mutations, sequences can be missing from one gene to another: this is called deletion
In yet other mutations, extra sequences can be added, often copies of short sequences, this is called duplication

How common are mutations in the Covid-19 virus?

This virus just has one strand of the genetic material RNA
This strand though has 30,000 nucleotides
Already scientists have identified 13,000 separate mutations
Although this might seem very high, the level of mutations is 6 times lower than in the influenza virus

What are the potential consequences of Covid-19 mutations?

Most mutations will have no consequences in terms of the infection
Even so, identifying such individual mutations can be very helpful in tracking the spread of infection between people
Of those that do make a difference, some mutations can affect the transmissibility of the virus (ie how easily it spreads) and others the severity of the infection
Early on in the pandemic, one mutation (OK it’s called D614G) was thought to be responsible for altering the spike protein on the surface of the virus that causes it to stick to human cells (and is the bit that most vaccines are directed against)
This mutation is now present in 80% of Covid-19 virus samples studied
The Chilean outbreak is thought to be due to further mutations in the spike protein gene making it even more sticky to human cells
There are other mutations, associated with a deletion of some of the virus’s genetic sequence, that make it less infectious
A study from Singapore in the Lancet in August suggested that that country’s lower death rate may be due to a deletion which produces less severe disease

The results were impressive-Singapore has lowest fatality rate in the world:

What is interesting is that mutations in the virus are likely to occur in response to how humans combat the infection. There could be both beneficial and harmful consequences:
- Beneficial: Consider for example there are two mutations: the one that causes very serious infections and the other that causes mild infection. People carrying the latter are more likely to spread the infection and thus that version of the virus will become more prevalent.
- Harmful: There are several examples of viruses mutating to try and overcome our body’s immune response
We should not forget that significant (but what significant means is difficult to be precise) mutations in the virus could affect the success or otherwise of any new vaccine
Although at the moment most vaccine researchers believe their vaccines should be resilient against the types of mutation currently recognised

How common are mutations in humans?

The answer of course is immensely common, each one of us probably has millions of mutations
Many of these mutations affect how our immune systems fight infections
The interesting question is therefore to ask if mutations in these immune genes explain why some people have more serious infections than others
The short answer from a vast number of research studies is yes: differences in these genes between people are linked to various dimensions of the outcome, including mortality
An example of a recent study is the one referred to below from the USA that showed that some people have a mutation that reduces the body’s production of interferon, which is our natural anti-viral drug.

Indeed, other studies have shown that an effective interferon response is necessary to fight this virus
To be honest, at first sight knowing that people who have more severe disease than others have a genetic basis for this might seem not that helpful, as we cannot change our genes

But what this kind of research can do is to help suggest new drug possibilities. Just yesterday came a press release from the biotech company ILC Therapeutics for an inhaled version of interferon that might be a useful new drug
This follow from another small UK study in July of the use of another type of interferon which showed an 80% reduction in the likelihood of severe complications
These are early days and more evidence is needed

Conclusions

There has been a massive amount of research into the genes that:
- allow Covid-19 to invade and cause such mayhem
- impact on our immune response
None of the research findings individually will be a game changer, there is a very complex jigsaw of how all the pieces fit together
A better understanding of the mutations in the virus can help in tracking the infection both over time and between regions and local outbreaks
More importantly these insights from genetic mutations can help focus attention on novel approaches to treating the infection

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Covid-19 Immunity Re-infection

Hong Kong report a man catching Covid-19 twice: no cause for concern

Post author By alansilman
Post date 25th Aug 2020
No Comments on Hong Kong report a man catching Covid-19 twice: no cause for concern

The Journal of Infectious Diseases yesterday issued a press release highlighting a report they had accepted for publication. In that report a young Hong Kong male who had definite but mild Covid-19 in March, was tested positive 10 days ago for a different strain of the virus-the first such case globally. The Hong Kong scientists suggested this should cause concern about immunity following infection, although other scientists have been reassuring. What issues does this report raise?

A note about the public release of this report

The full scientific report is not, at the time of writing, available on the Journal’s website, so the details cannot be explored
This is not acceptable: if reports are going to be released to the public, then the full report must be available for scrutiny.
Note that in CNN’s news bar they falsely mentioned the case was a woman!

What is the significance of a single case report?

There have been 24 million cases of Covid-19 documented worldwide.
There have been cases suggesting people being ill twice but this is the first to show definitely a new infection.
Of course, other second cases may have arisen and not identified, but if there had been a significant number we would know.
The fact that this is the first is reassuring.

Should we worry that the second infection was a different strain?

There are new strains of the virus emerging all the time.
As said before in this blog, that is normal for a virus but interestingly Covid-19 shows less tendency to mutate than other viruses
If it hadn’t been a separate strain, identified by more stringent genetic testing than is usually done, then it would not have been possible definitively to say this was a new infection

Does this case prove that immunity from a first infection would not protect against a different strain?

It is already well known (and discussed in this blog on 28 July) that immunity can fall over time especially in cases of mild infection
What is not known is whether, despite falling immunity, when faced with a new infection, the body’s antibody and other immune protection mechanisms would still come into play
For sure, the more different the second strain of a virus, the greater the possibility that the existing immunity might not full give protection
BUT the antibody response may still give some protection across strains

The Hong Kong case is interesting because….

The young man had no symptoms the second time
Although he was positive on swab testing the second time confirming the presence of the virus, he may have had an antibody response which protected him from any serious consequences
Thus (and not wishing to make conclusions on one case) perhaps it is reassuring that he did not become ill

Any issues about vaccines?

Not really, as the vaccines are designed to be active against the spike protein
There is no evidence yet that the spike proteins vary in different strains

Conclusion

Nothing is certain about this virus (perhaps justifying this blog!!!)
However, the case should not have received the publicity it did.

Tags Hong Kong

Covid-19 Immunity

“I have had the infection, how long will I will be immune for?”

Post author By alansilman
Post date 28th Jul 2020
No Comments on “I have had the infection, how long will I will be immune for?”

Some recent reassuring data

What was already well known about Covid-19 immunity:

Within 2 weeks of infection, people infected with the virus produced antibodies to the virus
The level of antibodies was greater in people
- who had symptoms compared to those who did not have symptoms
- People who had severe symptoms compared to those who had mild symptoms

What we didn’t know was:

How long would the antibodies last for?
Would those antibodies protect against further infection with Covid-19? (Not all antibodies ‘neutralise’ the virus – ie they are present but do not do anything useful)