Covid-19 infections are on the increase, many people are now getting their second or third Covid infection but now with Omicron BA.5* as the main culprit. Why is this happening, and why is there so little apparent protection through immunity either from previous infections and or from the vaccines?
*In this blog I mainly focus on BA.5 variant where there is separate information. Much of the available laboratory and epidemiological data do combine the results from BA.4 with BA.5, as they are very similar in their effects. Hence some places I will refer to BA.5 and other places BA.4/BA.5
How much more infectious is Omicron BA.5?
- We are used to new strains of Covid-19 virus emerging during the 2.5 years of the pandemic and rapidly becoming the predominant strain
- The reasons why this happens relate, firstly, to the new strains evolving to overcome the immunity mounted to older strains and, secondly, in some instances the new strains being naturally more infectious
- You may recall the ‘R’ number being the infectiousness score of a virus
- Indeed we were worried by the R for the original Wuhan strain creeping above 1.0 as it would represent a growing epidemic as from this slide from the BBC back in May 2020 – an R of 1.1 was ‘bad news’:
- As a comparison the R value for BA.5 is above 3!!
BA.4/BA.5 are now the predominant strains in many countries
- The figures below are from the USA (but other countries are the same!) and show that BA.4/BA.5 from being barely registrable on 7th May (blue arrow) by 9th July BA.5 accounted for 70% of all new cases (red arrow)
Could we face other, even more infectious, strains?
- Coming to terms with BA.5 is challenging enough but are there still other new strains to come?
- This of course would always be expected in a pandemic
- Indeed this week a new strain from India (unhelpfully given the nickname “Centaurus” and currently referred to as BA.2.5!) is increasing there and has been found in the UK, Germany and Netherlands
- The worry is that this new strain could bypass our immune system (see below) like BA.5
- For now I will focus on BA.5
How different is BA.5?
- Well here is the interesting thing!
- Genetically it is very similar to the other Omicron variants from BA.1 onwards that had been responsible for all the cases since the beginning of the year
- When I say the genetics are similar, I mean that the detailed DNA of the virus and its all-important spike protein are similar to other Omicron variants and, indeed, quite different from the earlier variants
- In the picture below, the relationship between the structure of all the major variants of Covid-19 since the start of the pandemic is shown
- Essentially how close to each other the different variants are positioned on this drawing is an indication of their genetic similarity
- It is easy to see that BA.4 and BA.5 are positioned very close to the other Omicron (BA) variants and some way from older variants like Delta
- But this is not the whole story!
- Although BA.5 is similar genetically, the same cannot be said for the body’s immune response
- In practice the body’s immune system ‘sees’ BA.5 as no more similar to the other Omicron variants than it does to the original Wuhan variant
- Look at this picture where a laboratory examined the immune patterns of the different Covid-19 variants
- In simple terms the closer two variants are placed in the diagram, the more likely the body’s immunity to an infection from them is similar
- What this picture clearly shows is that (to me surprisingly!) BA.4 and BA.5 are very different from the other Omicron variants in this respect
- As a consequence, the immunity from a prior infection say with the first Omicron variant BA.1 (we may have caught in January this year) would provide less protection against BA.4 or BA.5 than it would do against the original Wuhan variant!
- Why is this so: basically BA.4 and BA.5 have a few extra crucial mutations – not only in the spike protein – but in other key bits of the virus that allow the virus to stick to our cells and multiply
- Thus BA.5 can easily evade the immunity we have established with previous infections both from other Omicron as well as non-Omicron variants
Do these theoretical differences transfer into what is happening ‘on the ground’?
- The above all refer to research from the laboratory; do these worrying trends reflect what is happening in terms of reinfection rates?
- Thus one measure of how successful BA.5 is at evading our immune response from previous infections is to look at the risk of second infection
- Here are some data from France showing the risk of a second infection following a first infection with different variants within each particular wave (typically over the 2.5 years of the pandemic each wave lasts around 6 months)
- At the start of the pandemic with the Wuhan variant, reinfections during that first wave were very rare – so rare that there were headlines if there was a second case in the same person!
- With Omicron in the current wave, second infections, and maybe third or more, are increasingly common. Given the above information about the differences between the Omicron variants, this is perhaps not surprising
What about vaccines?
- It is well known a full course of vaccines, including boosters, protect against getting serious infection and this applies to all the known variants including BA.4/BA.5
- Similarly the vaccines do not protect against getting any infection, and that is as true, or more true, for BA.4/BA.5 than older variants
- Hence, we would not expect the current vaccines to prevent mild infections with BA.5
- There are new vaccines, designed to be more active against Omicron, which are being trialled, but my guess is they may still not be much use against BA.5
The big question is about severity
- Does it matter if our immunity to BA.5 is weak, if the infection from it is less severe and/or that our vaccines will still protect us from any severe consequences?
- As overwhelmingly most of the population at risk of severe infection from BA.5 (ie age over 60) have been vaccinated, it is very difficult to know what the severity would be if they had not been vaccinated
- There have been recent rises in the absolute numbers of cases admitted to hospitals in many countries, who have tested positive for BA.5
- These rises are driven by the growth in the overall number of cases and not by any difference in the severity of infection caused by BA.5 compared to other Omicron variants
- ie if the hospitalisation rate during the current BA.5 wave is say 1/1000 cases
- in a region with 1 million cases there would be 1000 hospital admissions
- in a region with 100,000 cases, there would be 100 hospital admissions
But what about long Covid?
- What causes and drives ‘long Covid’ is still a mystery
- There is no evidence that any particular variant is associated with a greater risk of long Covid than any other variant, and that is just as true with BA.5
- But recent data from the USA suggests that the likelihood of having long lasting symptoms following an infection with Covid, increases with each infection
- This study published last week does have some weaknesses and it may be that by chance alone, the more bouts of infection, the greater the chance that one will have longer lasting symptoms
- Many people will though now be having a second or even a third infection from BA.5, because it is so much more infectious – and this theoretically increases the likelihood of long Covid
- It does not seem likely that BA.5 on its own poses a greater risk of long Covid
Conclusion
- It is certainly the case that BA.5 has shown we are going to have to live with the risk of having repeated minor infections with Covid-19 and there is no obvious end in sight
- Existing vaccines and even previous infections do not offer the protection against mild infection with all its consequences including the risk of long Covid
- Mask wearing, which was compulsory in many situations and now only advisory, absolutely cannot be off the agenda
And finally..
The author of this blog succumbed to my first infection a month ago, nasty but fortunately short-lived but may have coloured my views a little!
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Making sense of CoVid-19 with Silman 