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Evusheld, long lasting aspects, and possible side effects

frozenborderline

Senior Member
Messages
4,405
research Evusheld in the future but do not have time today. If it is an infusion like you said, are both of the MAB drugs given at the same time (meaning are they mixed together into one formula) or are they given in two separate infusions? If they can be given separately, this is better from an anaphylaxis perspective.

Also with infusions, the minute you have ANY allergic symptom (even if your throat or ears felt itchy), they would immediately stop the infusion and give IV Benadryl (or anything else needed). It would have to be given in the hospital with nurses monitoring (if there is an anaphylaxis risk
It's a muscle injection but in other ways is the same as mabs... I don't know how they make the dose low enough to fit in a single muscle injection butbyeah it's two mabs
 

frozenborderline

Senior Member
Messages
4,405
have an appt with my main doctor in about a month and I will ask his opinion re: Evusheld (although his feedback would pertain to my specific situation and not to anyone else).

efinitely agree that we are all individual on this and my decision re: the vaccine was solely my own (based on my research and conversations with my doctors). Like you I have a history of severe MCAS (with history of anaphylaxis) but if this was the sole factor, I could have gotten the vaccine in the hospital and stayed overnight to ensure that there was a safety plan if I had anaphylaxis.

The bigger issue (for me) was re: my known history of Lambert Eaton Syndrome (LEMS), Autoimmune POTS, Hashimoto's, etc. Every aspect of my illness turned out to be autoimmune and it was three years of infusions & treatments for autoimmunity / immunosuppressants that led to my remission. The most risky thing that I could possibly do would be something that is extremely immuno-stimulatory like a vaccine. It could end my remission forever and I could not take this risk
It's tricky. I have pretty severe reactions to a lot of things but the research i did made me think the tradeoff with novavax and evsuheld might be worth it. I need to be able to go to doctor appointments without worrying about getting covid and long cogid is the main thing. Otherwise I'd just mask up and stay home.

I have honestly felt like even paxlovid being available would make me a bit more comfortable with the possibility of getting covid without immunization but I'm not sure if paxlovid interacts with my meds.

I think evusheld is so safe generally that even the most cautious and vaccine sensitive people have gotten it. But I just am spooked out by how it's made to be long lasting in the body. On the other hand it's derived from convalescent plasma antibodies that are semi natural and then augmented some... so maybe it can break down similar to igg... speaking of I have scig and I'm supposed to get ivig which could help protect against covid ...
 

frozenborderline

Senior Member
Messages
4,405
"
2022-05-03-how-evusheld-works-asm-1.jpg
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2022-05-03-how-evusheld-works-jnlimm-1.jpg
But… but… but! How exactly did they get the antibodies to have such amazingly long half-lives?! Following the references in their bibliographies led us to 3 papers (actually more, I just ran out of energy at 3) from 2002 - 2013 on this subject. [5] [6] [7]

It appears there’s a thing called the “YTE substitution”, which in the usual protein mutation notation makes the triple substitution M252Y/S254T/T256E (hence YTE). This was found to extend dramatically the half-life of antibodies, by 2-4x. Since these are somewhat older papers, they were of course done with antibodies that had nothing to do with SARS-CoV2. The discovery with Evusheld was that the technique carried over to SARS-CoV2.

Everybody points back to the Dall’Acqua papers as the source of this magic. But a quick read-through was maddening: although the results were described, they were not motivated. How in the world did anybody think to try that?! I’m mystified.

The Weekend Conclusion… and Some Remaining Puzzles
So the answer to our question of “how can it possibly work?!” seems to be, at the surface level:

  • The YTE modification is known to increase antibody half-life in the body, in this case around 90 days.
  • They administer it at very high levels, maybe 6x - 22x what is required, so after 2 half-lives (180 days) it’s still well above prevention-effective levels.
But there are still some questions that bother me:

  • How was the YTE substitution discovered? They weren’t just messing about by chance!
  • How does the YTE substitution work? What exactly is the physics of why antibodies with this triple substitution live so long?
  • Why isn’t this substitution done for every antibody infusion? For example, if we take bebtelovimab, the antibody infusion still in use to treat COVID-19 Omicron, would it be better if we did the YTE substitution to it?
So we learned something… and we also learned how little we know.

A typical day in science"
@Hip @Learner1 found some in depth discussion on it
 

frozenborderline

Senior Member
Messages
4,405
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Gingergrrl

Senior Member
Messages
16,171
@frozenborderline I will try to read over the rest of your posts later tonight or tomorrow when I have more time (vs. trying to rush through them right now) and appreciate the info :thumbsup:
 

Gingergrrl

Senior Member
Messages
16,171
@frozenborderline I'm sorry for the delay and I've now read through your posts and did a little research on Evusheld. But I don't have enough science background to give an opinion on the specific questions that you asked re: Evusheld and am hoping that you can ask your doctor.

I thought the reason adjuvants were used in some cases is that mrna vaccines already create a stronger immune response in other ways. And make more of the spike protein... so the non mrna ones need adjuvants to make up for that...

As far as I know (and I am about 99% certain), the mRNA vaccines for COVID do not have any adjuvants in them. They definitely have other ingredients that can cause anaphylaxis but not adjuvants that have been added to increase the immune reaction and make them even more immuno-stimulatory. All vaccines are already immuno-stimulatory (and that is of course their purpose!) but adding known adjuvants can increase the risk even further re: triggering autoimmunity.

I guess I had considered that a possibility but a rare one! The way my mcas manifests is very severe quality of life wise, but no anaphylaxis yet.

What I said re: anaphylaxis may not pertain to you if you have never had it (but I wanted to mention it just in case).

I should update my medical alert bracelet. I have one for covid.

What do you mean that you have a Medic Alert bracelet for Covid? I think I am just not understanding and apologize if it is obvious! My Medic Alert bracelet says "Anaphylaxis Risk" and "Adrenal Insufficiency: Needs Cortef" and a few other things.

We should get epipen but it's expensive even with insurance.

EpiPens without insurance are around $600 which is insane but luckily my insurance covers mine and it is only $50 for a two pack (of the brand name EpiPen). I do not get the generic b/c it involves more steps to use and it is more complicated which wastes time in a true emergency.

It's a muscle injection but in other ways is the same as mabs... I don't know how they make the dose low enough to fit in a single muscle injection butbyeah it's two mabs

I realized after researching Evusheld, and reading the package insert online, that it is two injections given together and not an infusion. From an anaphylaxis perspective, this is much more concerning to me b/c once you have given the injections, you cannot "un-give" them. Versus with an infusion, you can start at an extremely slow infusion speed and stop the infusion the moment that there is an allergic symptom and give IV Benadryl.

It's tricky. I have pretty severe reactions to a lot of things but the research i did made me think the tradeoff with novavax and evsuheld might be worth it.

I view each of these products on a case by case basis and what is right for me might be totally wrong for another person and vice versa.

speaking of I have scig and I'm supposed to get ivig which could help protect against covid ...

I Googled this too and everything that I found said that the current supply of IVIG now has Covid antibodies in it which can provide some protection (although I assume it is much less targeted compared to something like Regeneron).

From my research (again if I understood correctly), it seems like Regeneron would be given after someone tests positive for Covid vs. Evusheld would be given as a prophylaxis to someone who does not have Covid and has tested negative to confirm. Is that how you understood it, too?

It appears there’s a thing called the “YTE substitution”, which in the usual protein mutation notation makes the triple substitution M252Y/S254T/T256E (hence YTE). This was found to extend dramatically the half-life of antibodies, by 2-4x. Since these are somewhat older papers, they were of course done with antibodies that had nothing to do with SARS-CoV2. The discovery with Evusheld was that the technique carried over to SARS-CoV2.

I read through this part of your links but apologize that I did not understand it and the science is way above my understanding! I still have no idea how they dramatically increased the half-life of the antibodies in Evusheld.
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
How would one keep from get5ing covid or weigh that risk Against risks of these treatments
Wearing a mask everywhere is the best defense about getting COVID. I have been hearing from a lot of people lately who has avoided COVID for a long time coming down with it. It is too contagious and people are done with COVID and much to cavalier about mask wearing, even in medical facilities.

I think it's best to assume you will get it at some point and prepare yourself the best you can - wear a mask in all public indoor spaces and crowded outdoor places and surround yourself with those doing the same. Which is still risky. Evushield, IVIG and the vaccines offer some protection for many, with relatively low risk.
 

IThinkImTurningJapanese

Senior Member
Messages
3,492
Location
Japan
Wearing a mask everywhere is the best defense about getting COVID.

Mask wearing is at 100% were I'm at and we are still seeing 180,000 new cases a day of the Omicron variant. The government has even tried to get the public to remove masks outdoors due to the heat, but people have become habituated to them.

I wear a mask every time I'm inside a public place, even though I have rather vigorous immunity to Covid, it's not really a choice these days. The government here has never mandated masks, but businesses can legally refuse your access without them.

I've caught three Covid variants while masking up. I think @pamojja saved my ass with his research.