Reviewing the latest data regarding BA 2.86, another Omicron variant. When will this end?
Why is the immune response still skewed to the Wuhan variant, even with Omicron boosting?
Lasrado, Ninaad, et al. “Neutralization escape by SARS-CoV-2 Omicron subvariant BA. 2.86.” Vaccine (2023).
https://www.sciencedirect.com/science/article/pii/S0264410X23012537
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Timecodes
0:00 Intro
0:35 The speaker discusses the strange situation of the pandemic being declared over but cases still raging across the world, highlighting the need for more research and autopsy analysis to understand what is happening.
4:27 The video discusses the global spread of different variants of the Spike protein in 2023.
8:03 The original virus has a stronger antibody response after boosting compared to variants.
10:53 Understanding the different types of antibodies and their roles in the immune system is crucial in combating infections and ensuring effective vaccination.
14:28 The video discusses the significance of the COVID-19 pandemic during the winter period and the role of igg4 in the immune response.
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hi good evening to everyone thank you for joining me um currently trying to analyze where we are in terms of the pandemic we have a very strange situation where the pandemic has been declared over but yet we are still having raging cases across the world the CR question is what does it mean and sadly because we haven’t done adequate research and for me adequate research would have to include histopathology with autopsy analysis of deaths to try and understand exactly what is happening I’m going to be sharing some thoughts that I think are relevant to what may be happening now and why it could be relevant for the future so I’ll be looking at this paper neutralization Escape by sarov 2 Omicron subvariant baa 2.86 and this here was we have a publication date the 13th of November I think it’s been out for a little bit more than that time um but this is the date on it so we’ll come back to that paper in just a few minutes and I’ll I’ll well be sharing some thoughts about igg4 um and just an explanation about it as well as we look at what could be happening in the context of the pandemic additionally I plan to look at some data from Finland to try and understand what’s happening in a place where they’re actually measuring and looking at cases so before I start just a reminder for anyone who is interested coming up quite shortly diabetes coid and vaccines why autoimmunity is so critical I think this is a very very important topic because I anticipate that diabetes is going to become it was already a global epidemic I think that it will be accelerated in the context of the pandemic and then just looking at some of the reasons around it so getting back to this immune storm about coid 19 we are currently in very complex times we have a situation where from a political and from a a corporate point of view many people would prefer for the past to just be behind us and we move forward our problem is is that we still have circulating virus and once that is occurring we then have to question what are the longer term implications that’s really all I’ve been saying from the start don’t just assume let’s look let’s study let’s try and anticipate in whatever way we can what could be coming next so let’s get back to the point about the paper here so I’m going to share with you this uh neutralization escape and what they were looking at here is they were anticipating this new variant ba 2.86 being able to spread because it had evaded in terms of it’s um it’s in terms of the changes on the uh on the virus Spike protein it had over 30 mutations on that Spike compared to ba2 and xbb 15 and so they were worried that it might evade neutralizing antibodies induced by vaccination or infection and so they were comparing it to the other variants that were out there at the time I’ll I’ll show you uh a bit more detail here about what exactly is happening across the world with regards to the to the variance and the spread of variance because it highlights that we’ve got a real problem so this is looking at the global transitions of the different variants that you have and here you see this is looking from April 1st all the way through to September 30th so this is over about a 6mon period here uh this was in 2023 and you can see that this red variant was X bb15 and that has gradually been decreasing this one that has remained relatively consistent uh this light blue one is xbb um 116 this one here that has been expanding significantly across the world uh this purple one here is the I think when I look at the slide it’s the EG 5.1 and at the very top here what you can barely see is a slight blue Mark for the ba 286 right at the very top here so it was only just starting to evolve and they were concerned about it because of the the transitions of um of this variant so these are important things and when you look at the emerging variants across different parts of the world here you can see the countries where the emerging variants are most commonly sampled this was in China they primarily have EG 5.1 Australia similarly has EG 5.1 Sweden as well so across the world EG 5.1 is the main the main variant except probably for South Africa and you can see here in South Africa the ba 2.86 seems to have taken a bit of a surge so this is something that we’re seeing happening across the world it’s important to acknowledge for those who were stating that this was being driven by the unvaccinated cohorts I think it’s very clear now that that probably was not accurate science and this is where the politics and the science get compounded and it caus is for lots of problems as we have said before what I want to do now is highlight what exactly they saw with regards to looking at ba286 and the impact that this would have against uh antibodies so here they had a cohort of people this was not a a large cohort of people and they were looking at whether or not first this line is if they took the balent booster at the time and this was if they didn’t so these are people who have been vaccinated and boosted this is now the most recent bivalent booster um that has um has come out which is a combination the Omicron and the the original um original original virus or Spike protein and when we look across here in terms of the balent booster you have here this is the wa 2020 so this is the original variant and at this end here is the ba 2.86 and they’re doing this across all of the periods in this this is the Baseline this is at month six with no infection and this is at month six with infection and in case just to make sure you can see the numbers here so at Baseline here um with the booster it was about 6 6,172 the highest response from an antibody point of view this is what caught my attention was still the original virus even though we have all these variants and you can see down here they’ve gone through all the variants ba125 xbb and finally have B ba 2.86 so even though this is a more recent variant or even the xb16 down here the Ron variants have a weaker response after boosting than the original and this was part of the concern that I would have had where you have this immune imprinting where even though you are facing a different kind of virus your primary response is still to the original virus and you can see here that at month six with no infection this has come down a bit to 10,000 and you see this gradual fall across these um antibody levels when it comes to month six with infection this number jumped to 35,000 from 16,000 that’s almost double and what they were happy about I guess was the fact that VA 2.86 went from 304 um to here it went to 979 and this is uh this was what they wanted but again you can see there’s a huge difference in terms of the response to the uh original variant and this is what we call immune imprinting now one important part of that question that hasn’t been adequately answered because they were looking to see whether or not the antibody neutralizes the virus so they infect cells with it to look at it but here is the question that has been missed over and over again it’s just been talked about from the scientific Community but but the relevance of it we haven’t fully understood and this is to do with the IGG response now what they had looked at before was was looking at total IG but here is an important study that showed that when it came to infection after this is postc dose po post third dose of vaccines what they found here with igg4 was a huge jump a 38 times jump with igg4 levels so igg1 stayed stable there is some increase with igg2 ig3 actually decrease now one and three are the ones that tend to trigger the immune system igg4 tends to be the one that is immune tolerant it tells your immune system not to respond and this one jumped 38 times actually when we look at this is an example of our antibody profile you can see here IGM IG D IG G IGA and IG this is the one that responds usually first to an infection and IGG is the one that is usually long-term infection response but IG can be broken down into four different categories IG 1 2 3 four the one and three are the main ones that usually trigger the immune system to respond to a foreign virus or bacteria ig2 we’re not quite sure about it doesn’t tend to be so much relevant at the moment but igg4 is the one that triggers tolerance so it helps your immune system to not respond to what it thinks is no longer a problem like what I said beekeepers get when they’re continuously stung by bees they tend to have high igg4 so this is what we’re worried about is causing the immune system to not respond as well when it’s faced with infection and that could explain why we see such high circulation of virus in regions that have high vaccination levels so these are important things that we have to understand I think that why I’m concerned is that if we don’t fully understand the immune mechanisms that are occurring how do we know that even mild infection should not be taken seriously because in many countries there is no concern about the spread of infection as long as it’s not severe coid 19 but suppose it still is relevant suppose it still makes patients die but just not in the same way is that not a problem is it that patients blocking icus is a problem rather than the fact that they die this is an important question that we have to answer in order to to be clear now I also want to highlight one more part of the interesting puzzle and this is data from Finland I’d seen a a news um article from Thailand medical news that caught my attention and they were looking at here the number of cases with regards to coid 19 it starts all the way from 2020 and this is the bit that I was interested in here deaths temporal related to Corona virus within 30 days okay so within 30 days what is actually happening when you look at the period here so this is the period here now this is from September uh 2023 you can see here that the cases are now starting to rise in case you didn’t notice it when it when we went down this is all the way down into August and so on you can see here that there are only 20s and 30s of cases zero deaths um only a few deaths related 1 3 4 but what’s happening in Finland now that is causing concern is as you roll down into September suddenly the cases are rising and also the number of deaths that are related within 30 days are rising and you can see that this is now into October where it’s starting to Peak so 26 cases 18 deaths 193 cases 12 deaths this is very significant because we are only now moving into the winter period and you can see here this is now the 25th of um of October 2023 Peaks at about 341 cases 10 deaths and this is 30 days so from there we don’t actually have the accurate numbers for this bit but this is indicating that we are facing still a very significant phase in the pandemic what what we need answered is the interaction with igg4 and this is the final image I’ll show you here and this one here is showing the different stages and you have to remember igg4 is primarily something that is an mRNA response it doesn’t happen so much with infection it doesn’t happen even with adenovirus uh VOR vaccines it’s primarily mRNA and I do explain that at a different time and this is original where blue represents Spike specific IGG and you can see in in infection or even in the um original just one dose primarily it’s IGG um one that is produced but by the time you have this point here no mRNA but no infection what you’re seeing here is the ig4 is occupying almost 45% of the immune response this has got to be relevant but we are unsure what that means in the context of infection and what I consider to be an immune storm that is Raging within so here is my final thought or my final concern if we are facing a situation where even with asymptomatic or very mild infection this is causing a immune storm that is not presenting as severe coid 19 with respiratory Illness but can still lead to severe disease and death within a time frame of up to about three months is that important do we need to know is it as long as the icus are not blocked it’s not important these are important questions for us to answer and as far far as I’m concerned they cannot be answered without adequate autopsy adequate ability to understand exactly what is happening especially from an immune perspective so these are my thoughts at the moment and expect that as these numbers continue to rise and the impact continues to hit there will eventually be a response that may not be what you think it is I think that this is going into a very scary time I think this winter could be quite challenging across the Northern Hemisphere let’s hope for the best but critically if we don’t have answers we’ll be unable to find mitigation Solutions have a great [Music] evening [Music]
