Author: alansilman

Around the world’s media yesterday (January 4^th) were reports of a new fast-spreading variant of the Covid-19 virus: ‘XBB’.   Within a few short weeks from its first identification in the USA, it had become the most common variant in that country.  A small handful of cases in the UK (and I am sure other European countries) are now being recorded.  New variants, though, have emerged regularly during the pandemic.  Why do scientists now believe that the immunity we have both from our vaccines and our previous infections might not protect us against the  new Omicron ‘kid on the block’?

*https://www.theguardian.com/world/2023/jan/03/could-new-omicron-variant-xbb15-fuel-further-covid-infections

How do we know about new variants? 

• All viruses mutate and this is especially true during a pandemic 
• Because of modern genetic tools, scientists can examine in minute detail the genetic code of the viruses that infect different individuals over time
• During the pandemic there has been a worldwide collaboration to undertake this exercise on a massive scale
• As a result we have a week-by-week analysis of the changing pattern of variants.
• Look at this picture from the Sanger Institute in Cambridge (UK) which shows the percent of each major variant identified at different time points

*https://covid19.sanger.ac.uk/lineages/raw

• The different colours represent different variants that have come and gone during just the past 4 months – the speed of change is vast!

What do I need to know about the names of the variants?

• Originally the variants were named after their first place of detection eg South Africa, but that was dropped given concerns about ‘naming and shaming’
• The place names were replaced by Greek letters applied in order of the Greek alphabet, starting with alpha and that is how the name Omicron* emerged
• More recently geneticists have used a series of letters and numbers  to describe newer variants which probably all derived from the first Omicron variant
• For the layman (and me!) these suffixes are confusing eg BA.5 BQ.1, XBB etc.  (It is OK to give up on these  and just considering them as colours is fine!)
• Look at this picture, which shows how the different major variants have changed in 5 countries between June and November 2022

*For the linguists among you, I have deliberately used capital O for Omicron as, in this case, it is used as a name!

The big question then is how much are we protected against the newest variants?

Surprisingly this is a very difficult question to answer, and scientists can only give an approximate answer.  For those scientifically minded amongst you the reasons for this difficulty are given below, otherwise just skip to the next paragraph!

• It was much easier to undertake clinical trials to study the effectiveness of the first vaccines in comparison with a dummy (placebo), because very few people had any existing protection
• Virtually everyone now has either been vaccinated and/or had a natural infection and when faced with exposure to a new variant we ‘start’ with some, although quite different, levels of protection
• In addition, comparing rates of new infections between people with different vaccine histories cannot easily consider our different risks of exposure depending with whom we have been in contact  
• The level of protection from vaccines, and from a natural infection, is not constant and we know wanes in time, but to differing extents in different individuals
• The information we have comes mainly from laboratory research 
  • These studies measure both the level of antibodies and how effective these antibodies are when blood samples are infected in the lab with different variants 
  • But the results may not reflect what happens in real life when we are exposed and become infected with newer variants
  • That is because when faced with a new infection in real life: (i) we have other forms of protection apart from antibodies and (ii) our antibody protection will be ‘awakened’ to increase the amount of antibodies
• There are very few studies from real life and such studies do need to separate the risk of any infection from the risk of symptomatic and severe infection

How useful is the 4^th booster?

• The most recent data comes from a clinical trial in Israel, following those who were given a fourth  booster compared to a control group. 
  • All the participants had had a third booster with Pfizer 
  • The research also compared the responses if the 4^th booster was Pfizer or Moderna
• The study collected both lab data plus the numbers who became infected
• The lab data looked at antibody levels weekly for 10 weeks
• The graph shows the levels of antibody starting at one week after vaccine; and then the level weekly over the over the next nine weeks. (100% was the level achieved at one week)

• As you can see there is a very rapid decline, to almost undetectable levels, at 9 weeks
  • The decline is greater with Pfizer than Moderna
  • We should note that antibody levels following any vaccine always decline with time; but hopefully to rise, as mentioned above, when faced with infection
• This research then looked at how effective the boosters were in reducing the risk of infection compared to those who had no 4^th booster 
• In the graph below, the blue bars give an indication  of  the rates of infection for those who had had the 4^th vaccine dose, compared to the rates in the unvaccinated control groups – shown in the orange bars

• As you can see, there is little difference in the rate of infection following booster: ie the 4^th booster added little to the existing protection achieved from a 3^rd booster
• There was better news when looking at severe symptomatic infection, with reductions of 89% and 71% respectively in the Moderna and Pfizer vaccinated groups compared to those who had no 4^thdose
• But these data were gathered when the predominant strains were those (such as BA.4 and BA.5) that  we would expect to have been resistant to the new bivalent vaccine 

Why the recent worry?

• First look at the data from London, UK: 
• There has been a doubling in the rate of infection between November and the most recent data (the 2 weeks after 9 December)

https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveypilot/23december2022

• This rise has been associated with a dramatic shift in the predominant strains from those that the new vaccines were designed for (especially BA.5)

• Whilst it seems likely that these new strains will lead to a rapid increase in the numbers who are infected, we just don’t know if these strains will pose any greater risk of severe disease than the previous Omicron variants: there is no reason to suspect they will 
• What did we learn this week, though, was in lab studies that our existing protection might offer little defence against these newest variants

• I should say that the headline is unusually dramatic, and maybe inappropriately so for a scientific paper!

Conclusion

• Some of you will remember we have been here before with alarms about new variants!

• The new data confirm what we already know – that vaccines do not stop the spread of Covid-19 infection
• Up to now, perhaps because the newer strains are milder, as well as the protection we have from vaccines and previous infections, the risk of severe infection remains very small 
• The development of new vaccines can only play ‘catch up’ and can’t match the emergence of new strains 
• Hopefully that will remain so, but it is right that we keep a watchful eye 

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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 7^th May (blue arrow) by 9^th 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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The media have been full of headlines about a tiny number of cases of the viral disease monkeypox.  What do we know about it, why has there been a recent surge and, given the experience with Covid-19, should we be getting concerned?

What is monkeypox infection like?

• Monkeypox is a viral infection that causes flu-like symptoms
• It also causes swelling of the lymph nodes
• It has a characteristic blistering rash especially on the hands, feet and face
• Most people recover within 2 weeks

Is there more than one kind of monkeypox?

• Like Covid-19, there is more than one genetic strain
• There appear to be 2 major strains, one predominant in Western Africa in countries such as Ghana and Nigeria, and the other in Central Africa in countries like Democratic Republic of Congo
• The Western Africa strain has a very low mortality – even in poor rural populations – of around 1%, whereas mortality is much higher – 10% – from the Central Africa strain
• Fortunately the strain identified as causing cases in Europe and America is the milder West African strain

Why have public health experts got excited recently?

• Basically up to the last week or so, cases of monkeypox were only seen in Africans or in people from Africa who had spread the infection elsewhere
• The recent concern is that the new cases in Europe, Australia and North America do not seem to have had any African contact 
• Obviously, the number is growing but around 200 cases have now been diagnosed in the past week outside Africa which is more than the entire total of non-African cases diagnosed since 1970
• Why this should be so is unknown

How does monkeypox spread? 

• Monkeypox spreads differently from Covid-19 
• Basically it requires much closer contact 
• Also – unlike Covid-19 –  asymptomatic spread, ie catching the disease from someone without symptoms at the time of contact, is (or was) very unusual

Anything unusual about the new cases in Europe?

• As mentioned above, the lack of contact with an affected African individual is very unusual 
• Secondly, and at this stage only based on individual reports, there does appear to be asymptomatic spread, which could be worrying
• Thirdly, the recent cases have been proportionately greater in gay and bisexual men aged 30-50
• Whether this suggests that it is transmitted by sexual intercourse is unknown, but monkeypox had not been thought to be a sexually transmitted infection

What do we know about the monkeypox virus?

What about the connection with smallpox?

• This is probably the good news bit!
• Smallpox and monkeypox viruses are closely related
• Smallpox was only transmissible from person to person and hence a widespread international vaccination campaign led to the complete eradication of smallpox
• The last case of smallpox in the world was in Somalia in 1977
• Thus for decades there have been no new cases of smallpox and there is no need for anyone now to be vaccinated it
• Studies from Africa show that smallpox vaccine provides 85% protection against monkeypox which is good news for older generations who have received this vaccine
• Interestingly smallpox vaccines are used as a treatment for new cases of monkeypox, as well as for protecting close contacts
• There are also specific monkeypox vaccines that have been developed for use in Africa, which seem to be very effective with low risk of side effects

The outstanding questions:

• If this virus is now spreading from asymptomatic cases, that will make quarantining and containing spread more difficult.
• Whilst older people will have been vaccinated against smallpox, and hopefully protected against monkeypox, if any kind of outbreak takes hold it could it spread quite quickly amongst generations who were not vaccinated 
• Remember it is a mild disease, but I’m not sure that any country would wish to see an outbreak, or any individual developing an infection, even with ‘only’ a 1-2 week duration of being unwell, given what we have all gone through with Covid-19!

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As the original Omicron variant continues to mutate, its greater ability to transmit has been offset in terms of the public health risk by (i) the milder illness it causes and (ii) the protection against severe disease from both natural infection and the current vaccine regimes.  However, should we now be worried about the new variants now spreading from South Africa to Europe and North America?

A bit about the original Omicron 

• The original Omicron variant when originally identified was not thought to have significant subvariants 
• Then in South Africa, in late 2021, 3 sub-variants of Omicron were identified, and are now referred to as BA.1, BA.2 and BA.3
  • These 3 had many different genetic mutations from the original Omicron, but also differed from each other
  • All these subvariants were associated with mild infection, although some of the protection against serious infection will be a consequence of immunity from either, or both of, vaccines and natural infection
• One or more of these variants rapidly predominated in Europe
• Indeed in the UK, during the 2021/22 winter peak of Omicron, around 95% of new cases reported were from BA.2
• There have been many reports now of people having a repeat attack from one of these original Omicron variants, but these have also been mild
• As a consequence, and despite the greater transmissibility of Omicrons BA.1-3, the milder disease consequent on our natural and vaccine immunity led to the lifting of behaviour rules and also a reduction in self testing which has had a knock-on effect on our not knowing the exact numbers of cases

What are Omicron BA.4 and BA.5?

• These are two quite different subvariants of the original Omicron BA.1-3
• Both were first identified in South Africa this year in two provinces: BA.4 in Limpopo in the far north and BA.5 in KwaZulu-Natal in the south east. 
• These two subvariants have some of the same mutations as the original Delta variant
• They also have different mutations on the spike protein to other Omicron subvariants,  which makes them more sticky onto human cells and hence more likely to lead to infection
• Thus, not surprisingly, there has been a massive increase in the proportion of cases in South Africa due to these subvariants over a very short time
• As shown in the picture below, almost all cases in South Africa now are either BA.4 or 5

Have these variants spread to other countries?

• Indeed yes and they are already contributing to a growing proportion of cases in the few countries that have been able to test for these

• Thus they probably amount to 15% of all cases in the UK (both variants combined)

Do we need to worry about these subvariants?

• Obviously, the big question!
• Compared to the original Omicron subvariants, BA.4 and 5 are probably more transmissible so the absolute number of new cases is likely to increase (compared to what the numbers would have been if BA.1-3 were predominant)
• Indeed, the number of notified cases in South Africa has risen from around 1000/day in mid-April to over 10,000/day by the end of last week, a tenfold rise in less than 4 weeks
• As a consequence of the numbers alone, this has had a knock-on effect on the numbers being admitted to hospital; and indeed the challenge of increasing sickness amongst South African health workers with the new sub variants
• As with the original Omicron subvariants, the disease though is predominantly mild

What about protection from vaccines and previous infections with the older Omicron subvariants?

• That at the moment is the big unknown
• Experts are asking if this surge in cases in South Africa means that these new subvariants can evade our acquired immunity?
• Alternatively is any protection from the vaccines/previous infections waning? Hence the increase in cases from these subvariants just represents that phenomenon and would have happened with any circulating variant.
• This is where a research paper published this week might provide some insights to address this issue:
• This is what the research did

Their conclusions as summarised below was interesting and perhaps sobering!

• In brief the ability of this virus to mutate means that herd immunity is not an achievable outcome 
• Just giving boosters of the existing vaccines derived from the original Wuhan variant may not be of much benefit

But to some extent this is the situation with seasonal flu – except that Covid-19 mutations seem to be occurring in a 6-month cycle (see this picture from this week’s Nature)

And finally are there new more effective vaccines coming on stream?

• Before the BA.4/5 issue, both Moderna and Pfizer were already  modifying their mRNA vaccines to be effective against Omicron BA.1-3
• They have promised results by June 30^th
• I wonder if the BA.4/5 story means that the virus is mutating so quickly that major beneficial changes cannot be achieved with these new Omicron-derived vaccines
• The virus can mutate more quickly than vaccines can be developed to stop transmission

Conclusion

• Covid-19 is clearly here to stay and will continue to mutate
• The good news is that whilst repeat infections are likely, and may be impossible to prevent, the dire consequences of 2020 should not recur

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Despite the worldwide relaxation in Covid-19 mitigation and the awful situation in Ukraine displacing other news, that does not mean that Covid-19 has gone away.  What do the latest data show?

We cannot rely on the numbers of self-reported cases

• Regular readers of this blog will know that the number of self-reported or health care professional-reported cases cannot be relied on as a source of the true underlying trends
• Such information can only be gained from epidemiological studies of random samples of the whole population. In the UK, we have been fortunate to have 2 such studies: 
  • REACT which which has nearly 100,000 people sending in swabs every month in England
  • The Office of National Statistics (ONS) Covid-19 Infection survey which has 180,000 people sending in swabs every fortnight from all 4 countries in the UK
  • These studies therefore pick up anyone who is positive, whether or not they have symptoms and whether or not they did – or did not – report (for example) the results of a home lateral flow test
  • These studies can usefully estimate the total number of Covid-19 cases there are likely to be in the whole country
• This is the most recent data:

• Thank goodness we have stopped seeing these meaningless reports in the media of the number of reported cases
• I am sure that the same under-reporting is a worldwide phenomenon, we are just fortunate in having UK funding of these population studies*

*Although the Research Lead for the REACT study told me on Friday that government funding is ceasing for that study at the end of the month as they believe it is all over!

What do these epidemiological studies show?

• In England there has been very little change in the rate of new cases since the beginning of the year
  • Monthly rates hover around 4% or 1 in 25 of the population
  • If anything, last week saw a small rise

• In Scotland the recent rise is more pronounced and is unlikely to be due to the normal ‘up and down’ in such data

• A similar recent rise has been seen in Northern Ireland, with 1 in 17 of the population being positive 
• These differences between the UK constituent nations are also mirrored by different trends in different parts of England

• Thus for example the Southeast has had no fall
• The current higher rates in London and the Southeast might reflect their greater social mixing and work patterns
• There have also been differences between age groups in the trends: 

• The take home message is that since the start of the year there has been a decline in rates, especially in children, but conversely a slight rise in those over 50
• Childhood rates had been very high and they are now, as expected, approaching those in the rest of their households
• The slight rise in the older age groups might reflect the expected greater mixing following the relaxation in mitigation measures

Do we know anything about hospitalisation rates?

• Trends in hospitalisation rates based on the national reporting systems should be a reasonable indicator  of the underlying trend in the number of new severe cases 
• As is well-known, hospitalisations have been falling since the beginning  of the year due to a combination of the success of vaccines and the dominance of the milder variant Omicron
• Indeed declines in the number of people being admitted with Covid-19 have been observed in all the major European countries 
• However in the last couple of weeks there has been a worrying slight increase in the number of cases admitted in the UK, but not in other major European countries 

• By contrast, in the past week across Europe there seems to be quite a marked increase in the number of reported cases
• It will be interesting to see if these rates translate into more hospitalised cases over the next two weeks 

Is Omicron still the main variant?

• Indeed Omicron accounts for 99% of all UK cases 
• The interesting thing though is the proportionate increase in the sub-variant BA.2*
• This variant is even more transmissible than ‘regular’ Omicron but does not differ in severity
• The figure below shows the estimated percentage of all new cases in England due to BA.2:
  • The green blobs – show the daily laboratory  reports of the proportion of samples that are BA.2 positive
  • Because the numbers tested each day are quite small, the statisticians allow for this by giving a range – the green vertical lines
  • No BA.2 cases were identified before mid-January, whereas by 20th February the proportion of BA.2 was approaching 50%

*Despite its name BA.2 is not an advert for the world’s favourite airline!

• It seems that the vaccine protection against BA.2 is the same as against other Omicron variants. 
• Whether previous infection with the latter protects against further infection with BA.2 is not known, but certainly there are many reports of people having a second Omicron infection 

Conclusion

• Just because Covid-19 is not in the news, it has not gone away and might be increasing
• No new variants of concern have arisen and the latest variant BA.2, although responsible for keeping the virus spreading within the community, is not causing any specific new medical concerns 
• It is obvious that the overall risk of a significant infection to any fully vaccinated individual is based on the combined effects of the local infection rates and the severity risk of the predominant current variant(s)
• There is no evidence of the risk declining and possibly a small increase in risk, but mainly of mild infection
• Thus, despite Covid-19 not being in the news, no reason to change whatever feels individually comfortable in mask wearing etc

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I was looking at the data on the rate of new cases in different countries.  This showed the Faeroe Islands – a group of islands to the north of Great Britain – currently have the highest rates of infection in the world. On 25^th January they reported 913 new cases, equivalent to almost 2% of the population, just in 1 day

• To see how these rates are so much higher than elsewhere, look at this graph:

• The key question is what is the variant underlying these phenomenal rate rises and does it pose a risk for the rest of Europe and indeed the world?

What variants are infecting Denmark?

• The key variant is the so-called BA.2, which has mutated from the original Omicron variant, (correctly referred to as BA.1)

• Over a very small number of weeks BA.2 has become the most common variant in that country
• Below is a screenshot (apologies for poor quality) of the graph from the main Danish lab showing the takeover by BA.2

• It thus seems highly likely that BA.2 is more infectious, explaining the growth in the number of cases
• My suspicion is that, given the close links with Denmark, the surge in the Faeroe Islands is also due to BA.2

Is there any difference in the infection caused by BA.2?

• The variant is even more infectious but not more severe than BA.1 Omicron 
• There hasn’t been a surge in the number of deaths from Covid-19 in Denmark 
• Although there has been an increase in the number admitted to hospital, this is only to the extent that is expected from the increase in the number of cases
• Further weeks of observation on this new variant are needed to confirm these reassuring observations 

What about other countries?

• This is the strange thing!
• In England, which has one of the best developed PCR laboratory services, there have only been 400 cases of BA.2 identified up to last week despite the first case being identified as long ago as December 6^th
• I cannot find any data about BA.2 in France, which also is in the middle of a major surge
• The first handful of cases of BA.2 have now been identified in the USA
• Why I think this is very strange:
  • Given the data from Denmark, a bit like the situation when Omicron (BA.1) arrived, we might have expected a very rapid takeover by the new BA.2 variant in all countries
  • This takeover has not happened yet in any other country, suggesting that outside Denmark, the cases of BA.2 were not so much more infectious than BA.1 – which has its own very high transmission rate

What about vaccination rates?

• As frequently described in this blog, vaccines offer little protection against transmission of asymptomatic infection, but do offer some
• For what it’s worth, Denmark (and the Faeroe Islands) have very high population rates of vaccination (2 doses) compared with the rest of the EU and the UK

• Experts do not believe that the vaccines are any more, or any less, effective against BA.2 Omicron than they are against BA.1 Omicron 

A final comment on how is BA.2 identified?

• First identified in the UK by the national genetic screening of samples sent for PCR testing
• Initially considered just one of several sub-variants that typically will have arisen by chance from Omicron and possibly of little significance 
• BA.2 has several different mutations compared to the original Omicron (called BA.1)

• One of these differences is that the BA.1 variant of Omicron has a gene missing in its spike protein (the so-called  ‘S-gene dropout’)  – this  dropout is not seen in the BA.2 spike protein  
• S-gene dropout is easy to detect in a laboratory, and is widely used to decide if Omicron is present
• The worry is that the laboratories round the world have been relying on this approach to diagnose Omicron: this strategy would therefore miss detecting BA.2 Omicron

Conclusion

• Is the BA.2 surge in Denmark a worry for the rest of Europe and the world is not easily answered
• The infection the variant causes is no more severe and perhaps if it infects more of the population more quickly, then maybe such countries will achieve the benefit of population-wide natural immunity 
• We also don’t know, but need to know, if this variant might lead to an increased likelihood of re-infection: ie for people who have had BA1; is there a greater chance of being reinfected with BA2 than a second dose of BA1?
• The WHO has labelled BA.2 as a Variant of Interest as opposed to a Variant of Concern.  
• This seems sensible, we have no need to panic but we need to keep a close eye on the rates of new cases especially if cases continue at their current high rates

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In the UK, with the pressure on hospital beds from Omicron being containable, the government announced last week a relaxation in the rules brought in to minimise transmission of infection.  In this post I consider why the data might not support this decision

What is happening to infection rates in UK, Europe and North America?

• There is no shortage of data on reported infection rates in every country
• In this graph I show the rates of infection since the start of the Omicron wave in 5 selected countries 

• The broadest conclusion is that over the past 2 weeks, rates have certainly not fallen, and in France indeed are rising
• Many other European countries are also showing even more substantial rises
• in total, cases in the past week are 15% up from the previous week across the whole of Europe

• We need to be careful, though, as these data are of ‘confirmed cases’:
  • If the number of people seeking to be tested falls, for reasons perhaps related to the logistics of obtaining a test – 
  • Then (everything else being equal) these published numbers of confirmed infections may underestimate the true number of cases
  • The opposite may occur, of course, if tests are easier to obtain
• As an example, though, the UK government on 11^th January removed the requirement to have a PCR test if you were asymptomatic despite having a positive lateral flow test
  • Whilst this was not unreasonable given the demand for PCR tests, it inevitably could have resulted in the initial fall in the number of PCR positive cases
  • I have shown, that after January 11 (red arrow on the graph above), there was a fall for a week but that this fall has now levelled off 
  • Given the upward/flat trend in other European countries, I question how accurate are the UK figures, reported daily in the media.
    
• Thanks to KS for also reminding me that another inaccuracy in the daily data from England is that the number of cases reported excludes anyone who has been registered as having an infection in the past: reinfection

Can we know the true rates of new infections? 

• A simple question but a bit complicated to answer (typical epidemiologist!)
• Fortunately, in the UK, there is the Office of National Statistics (ONS) weekly survey of a random population sample, using PCR tests on everyone in the sample – whether they have symptoms
• The most recent results, published 3 days ago, provide the best guide to the numbers of people who are positive on the day of testing in the 4 UK countries
• The graph below shows the data for England from December 1^st to January 15^th, ie in the period since cases of Omicron started to be seen in the data

• The data showed that on 15th January, it was estimated that 5% of the population were infected: 1 in 20
• Remember also a positive PCR does not absolutely indicate a current infection
  • PCR may take a few days to become positive
  • The PCR can then be positive for 2 weeks or longer 
  • Thus ONS in their data assume that across the total number of people who  are PCR positive today, the “average” date they caught their infection is probably about 2 weeks ago
  • Thus, their most accurate assessment of the rate of new infections is on January 1^st, which if sustained suggests that each week, at the start of the year, which is consistent with 5% of the population were developing a new infection
• Now look back at the first graph, which shows the flattening trend over the past couple of weeks
• Inevitably sophisticated data sets such as the ONS survey are playing ‘catch up’
• Over the next couple of weeks there may be an important downward trend in new infections, but we cannot be certain yet
• Conclusion: Difficult to be accurate but even if the weekly rate of new cases is now not quite as high as 5% of the population, it is unlikely to be much lower and the infection must be considered as still unacceptably widespread in the population

Should boosters not have impacted on these trends?

• An obvious question, but why haven’t the rates dropped since the booster programmes have now been rolled out in many countries?
• We know that the main effect of the boosters is to reduce severity of the infection

• Indeed, the report this weekend from the USA showed that triple-vaccinated people had one third of the rate of symptomatic Omicron, (including those with just mild symptoms) compared to doubly vaccinated, which is great news
• But current vaccines do not have a major effect of preventing transmission
• The consequence is that being in a room of triple-vaccinated people does not preclude a significant risk of contracting the infection 

Is there a rationale for relaxing measures aimed at reducing transmission?

• A summary of the above is therefore that there is still lots of Omicron around which can continue to infect fully vaccinated people
• The data are still being collected on the chance of catching Omicron twice, but it won’t be negligible 
• For sure, Omicron is milder, especially in fully vaccinated people, and there is a line of argument that says transmission of an infection of that (low) level of severity need not be a public health concern
• But if we can reduce transmission even of this milder but highly infectious illness, without societal cost, why not?
• There is a Latin expression which underpins much of medical guidance: primum non nocere (first do no harm)  
• I mention that because wearing masks on public transport and other places, at a time when there is a background infection rate of 1 in 20, would seem to be a no-brainer
• For statistically inclined readers, rate of 1 in 20 does not mean that if you are in a gathering of 19 people, you are protected!  In fact, with that background rate, in any gathering of just 10 people, there is a 40% chance that at least one person will be infected

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