New variants versus new(ish) vaccines: which are winning?

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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