Evusheld, long lasting aspects, and possible side effects

Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
At this point I don't think evusheld or novavax are terrible risks compared to other immunization treatments against covid, or compared to effects of covid itself. However I do worry about one thing. i should like to ask an immunologist or a knowledgeable patient about this: if evusheld, the combination of two monoclonal antibodies made to be long lasting in the body, happens to cause a rare side effect or mcas reaction, will that reaction last for the whole time that the antibodies remain in the body, which is longer than many mabs? Even if the side effects are rare this is the one thing that concerns me. It is a type of biologic and is degraded similar to antibodies and natural igg in the body but it is also made to be particularly long lasting , which is good for protection from covid, but I guess i worry about what it means if one is the rare person to react to it.

I know there are some other mabs using the same technology to make them longer lasting. I know there are mabs that are short lasting which everyone seems to consider safe like regeneron.

I'm curious if the long lasting aspect would make evusbeld at all risky in rare cases of reactions and how immubologist would treat this. I may start a new thread for this.
@Learner1 you seem to know a lot about immune issues as does @Hip and @pattismith . What do you guys think about the problems with long lasting mabs like evusheld... they stay in the body for awhile but does that mean the side effects would necessarily last that long or does the body just stop rejecting them at some point

Evusheld and novavax and paxlovid are the three things I'm most excited for in terms of helping prevent getting even worse from covid. But I'm very frail so I do want to make sure that I am cautious about what decisions I make even if these are safer than the other vaccines.



.





I'm also more concerned with covid than evusheld, but I can be concerned about both, given how hyperreactive i am. Many things like vaccines and contrast I react to even when doctors, including me/cfs specialists, have said I'll be fine, so scrupulousness/scrupulosity? Isn't irrational totally.

The reason I asked is some of you seem to have a good understanding of a lot of immune mechanisms in particular so I thought you might know the answer to this. Not what the general side effects are or how safe evusheld is but rather what the risks of making the mabs long lasting might be if any, or if there are no risks compared to a short acting monoclonal antibody . I accept the risks are generally rare , my concern in this case is that if you have something that lasts for six months in your body and you do have a reaction, like an mcas reaction or immune intolerance of it In some ways, then would that mean you stay reacting for the whole six months? I've never had a drug that has a 90 day half life so this is a question I've never had to contemplate.
 
Last edited:

Learner1

Senior Member
Messages
6,253
Likes
11,580
Location
Pacific Northwest
, like an mcas reaction or immune intolerance of it In some ways, then would that mean you stay reacting for the whole six months?
Worst case, you do plasmapheresis and get rid of the offending antibodies.

Not to minimize your concern, but I do think precautions are in order. I did load up on quercetin, ketotifen, cromolyn sodium and benadryl before the shots and Evushield and for a couple days after. The 2nf and third shots made me feel awful, worse for the third one. The Evushield was much better, I felt a little tired but ok.

If your MCAS is that bad, perhaps looking into some other combo of drugs/supplements might be wise - see attached, or working on improving your microbiome - have you done a Viome Gut Intelligence Test ? Or reduced drivers?
 

Attachments

Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
Worst case, you do plasmapheresis and get rid of the offending antibodies
I think I could never afford plasmapharesis. I was interested in it as a general treatment for me/cfs, but I've never heard of it being covered by insurance and it's monstrously expensive.

So maybe the worst case would not be doing plasmapharesis which I certainly wouldn't mind if I needed it, but having a reaction and not being able to afford plasmapheresis.

Maybe an immunologist could answer this for me though. I mean in theory one can react to anything that is "foreign" but the monoclonal antibodies are biologics which degrade similarly to IgG just a bit slower so maybe even if one has an initial reaction it would be rare to have a reaction the whole time it's in one's body?

I don't exactly know how that works. Like I said I've never had a drug with such a long half life so I've not ever worried that a reaction would last a whole six months.
Interestingly even regeneron, the short lasting antibodies that even hard-core anti vaxxers seemed very comfortable with in the hospital , that is used for *acute* covid, are fairly long lasting , not as long as evusheld, but still pretty long ... about half as long I think. I will try and research it more but it seems like there is a favorable side effect profile for regeneron despite the long half life.

My mcas is severe, but its somewhat selective , there are people who react to chemicals and scents more than me and foods but I react terribly to airborne toxins/particulate pollution, mold and mycotoxins, and fairly poorly to some immune things like vaccines , at least since I've been sick. But no extremely restrictive diets or anything. So I can't predict what I'll react to. I am not very worried about anaphylaxis, just like i said, the possibility of a very long term intractable reaction.

I will ask my immunologist about it , even if it's a stupid question and I get laughed at for it.
 
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
Not to minimize your concern, but I do think precautions are in order. I did load up on quercetin, ketotifen, cromolyn sodium and benadryl before the shots and Evushield and for a couple days after. The 2nf and third shots made me feel awful, worse for the third one. The Evushield w
The problem for me with using mast cell drugs before a treatment is that I'm already basically maxed out on my doses for those meds. I'm at I think one of the highest possible doses of ketptifen , I take quercetin and cromolyn as well regularly and cyproheptadine at one of the highest possible doses. It is a good idea in general tho.

Even with those meds my trytpase and histamine are very high regularly. I think it's partially bc where I'm living is fairly moldy and toxic.

But also I have Hereditary alpha tryptasemia. Ihave a genetic component to this that makes it a bit harder to treat.
 
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
"The mean and individual concentration–time profiles for the components of REGN-COV2 — casirivimab and imdevimab — increased in a dose-proportional manner and were consistent with linear pharmacokinetics for single intravenous doses (Figs. S6 and S7). The mean (±SD) day 29 concentrations of casirivimab and imdevimab in serum were 68.0±45.2 mg per liter and 64.9±53.9 mg per liter, respectively, for the low (1.2 g) doses and 219±69.0 and 181±64.9 mg per liter, respectively, for the high (4.0 g) doses (Table S4); the mean estimated half-life ranged from 25 to 37 days for both antibodies (Table S5)"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781102/


I found this really interesting bc it's from an acute covid-19 MAB cocktail treatment. despite not being made to be a long term treatment, it is fairly long lasting. I think that the antibodies in evusheld have a specific modification to make them more long lasting, I forget the specific terminology, but MABs as a class might just be more long lasting even without that specific modification, maybe bc of the way antibodies in general are processed by the body, including endogenous produced antibodies... those antibodies may have different, longer lasting pharmacokinetics than most drugs. I hate having to research everything I put into my body bc of mcas and so on, but I have to admit this is somewhat interesting.
 
Last edited:
Messages
28
Likes
62
Histamine and MCAS seem to be closely related. I wonder if that may be the underlying cause? Don’t know, but the more I research this disease and the various treatments suggested, that seems to be an underlying theme. Histamines and MCAS are the driving force behind the various manifistations of the symptoms seen, and underlying individual predispositions are what is driving the variability seen in individuals. It makes more sense than any other theory and explains the inflammation that everyone experiences.

I just listened to this Dr., and it makes some sense. Whether that is the underlying factor, time will tell.
https://www.drtinapeers.com/mcas

Whether antibody treatments are the answer seem debatable to me.
 
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
Histamine and MCAS seem to be closely related. I wonder if that may be the underlying cause? Don’t know, but the more I research this disease and the various treatments suggested, that seems to be an underlying theme. Histamines and MCAS are the driving force behind the various manifistations of the symptoms seen, and underlying individual predispositions are what is driving the variability seen in individuals. It makes more sense than any other theory and explains the inflammation that everyone experiences.

I just listened to this Dr., and it makes some sense. Whether that is the underlying factor, time will tell.
https://www.drtinapeers.com/mcas

Whether antibody treatments are the answer seem debatable to me.
I'm not sure how your response relates to what I said. I'm looking at antibody treatments to protect against covid, not to treat me/cfs or mcas.
It is an obvious truism that high histamine is related to mcas.
 
Messages
28
Likes
62
I think your concerns about the “treatments“ or prevention are valid. Personally I use(d) Ivermectin when I am going on a plane or out and about as it has no immunological activity, it is a protease inhibitor which prevents replication. Omicron, as least historically seems to be a mild a case which confers immunity. Getting vaccinated seems to prevent the worst outcomes, but at the price of future outcomes. I prefer not to mess with the immune system as knowledge of how it works is poorly understood.
 
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
Omicron, as least historically seems to be a mild a case which confers immunity. Getting vaccinated seems to prevent the worst outcomes, but at the price of future outcomes. I prefer not to mess with the immune system as knowledge of how it works is poorly understood.
As far as I know, omicron still causes long covid at a significant rate.
 

Gingergrrl

Senior Member
Messages
15,850
Likes
46,943
At this point I don't think evusheld or novavax are terrible risks compared to other immunization treatments against covid, or compared to effects of covid itself. However I do worry about one thing. i should like to ask an immunologist or a knowledgeable patient about this: if evusheld, the combination of two monoclonal antibodies made to be long lasting in the body, happens to cause a rare side effect or mcas reaction, will that reaction last for the whole time that the antibodies remain in the body, which is longer than many mabs?
@frozenborderline I just saw your tag and re: Novavax, in my situation, it would be the worst option of the Covid vaccines b/c Novavax contains an adjuvant. The vaccines with adjuvants create an even longer & stronger immune response and this is specifically the purpose of the adjuvants. So for someone with a known history of severe autoimmunity like me, Novavax has an even greater risk of re-triggering my autoimmunity.

I actually do not know anything about Evusheld and would have to research it before commenting. Are you saying that it is a MAB drug (or the combo of two MAB drugs) similar to Regeneron except that it is longer lasting? Is it an infusion or injection (or some other modality of treatment)?

I would think that any anaphylaxis reaction (or severe allergic reaction) would be immediate or within a few hours so if the treatment were given at a hospital, they could be prepared with IV Benadryl and Epi. As far as longer term reactions, I would have to research Evusheld and ask my doctor his opinion.
 
Last edited:
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
just saw your tag and re: Novavax, in my situation, it would be the worst option of the Covid vaccines b/c Novavax contains an adjuvant. The vaccines with adjuvants create and even longer & stronger immune responses and this is specifically the purpose of the adjuvants. So for someone with a known history of severe autoimmunity like me, Novavax has an even g
Wow interesting, there's so much different info out there. I know I felt more comfortable with it bc it's a technology that's been in vaccines that I've had in my lifetime and also that the fda says it has less "reactogenicity", just in the general population less immediate side effects.

But truly, we are all so individual with this. I have mcas which could be considered autoimmunity and I have a lot of unknown immune issues but besides that I don't have any well defined autoimmune disease. With regard to this issue I would either get novavax or not get a vaccine bc im not comfortable with the mrna ones. It's not bc I believe a conspiracy theory like they alter your DNA but Moreso the amount of reactions I've seen people have to them with severe ME esp. That are long lasting. And it's a novel tech so there's a bit less precedent over time to see peopels reactions. So when novavax came out I thought "well maybe i will finally have a vaccine I feel comfortable with".


But I will have to do more research about the adjuvant now that you bring it up.

My mcas doctor is pretty good but she's a bit dismissive of concerns around vaccine reactions so idk about asking her about that. But maybe with. Evusheld she can explain it
 
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
actually do not know anything about Evusheld and would have to research it before commenting. Are you saying that it is a MAB drug (or the combo of two MAB drugs) similar to Regeneron except that it is longer lasting? Is it an infusion or
exactly what you're saying, yes.
Its a combo of two mab drugs, just like regeneron is, and all mabs seem to be *somewhat * long lasting already but not long lasting enough to be prophylactic. However with evusheld they have modified the two mabs with some kind of amino acid group, I forget the name for the tech, it's not totally novel and has been used in other mabs, and this makes it longer lasting. It's half life is 90 days and it lasts 6 months in terms of protection!
Whereas regeneron half life is something like 20 days?? Or 11?? I forget but while not as long as evusheld it's definitely longer than a normal drug. I'm trying to learn enough about evusheld and mabs in general to know whether to trust it since I don't have a doctor advising me on the details yet. And I've had doctors say things were safe and I still have bad reactions
would think that any anaphylaxis reaction (or severe allergic reaction) would be immediate or within a few hours so if the treatment were given at a hospital, they could be prepared with IV Benadryl and Epi. As far as longer term reactions, I would have to research Evusheld and ask my doctor his opinion.
Yeah I guess there is no option other than finding a doctor to explain it to me ...
 
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
I'm definitely not worried about anaphylaxis. I mean I'm generally at peace with d3ath (not in a suicidal way to be clear, just that I am religious and believe in an afterlife of some kind and my current life is not amazing, so I'm not afraid to pass on). However what really scares the heck out of me is becoming sicker long term. I'm right at the edge of what I can tolerate
 

Gingergrrl

Senior Member
Messages
15,850
Likes
46,943
Wow interesting, there's so much different info out there. I know I felt more comfortable with it bc it's a technology that's been in vaccines that I've had in my lifetime and also that the fda says it has less "reactogenicity", just in the general population less immediate side effects.
I've done a LOT of research re: the Covid vaccines, specifically in regard to autoimmunity and my own situation. From my research, and my discussions with multiple doctors (of different specialties), it was clear to me that vaccines with adjuvants create a longer & stronger immune response than vaccines without adjuvants because this is literally the purpose of why the adjuvants are added.

This is a separate and distinct issue from the technology or type of the vaccine (meaning mRNA vs. adenovirus vector vs. other types, etc). In addition, my research was specifically on autoimmunity and not on vaccine side effects or reactivity in the general population.

But truly, we are all so individual with this. I have mcas which could be considered autoimmunity and I have a lot of unknown immune issues but besides that I don't have any well defined autoimmune disease.
I definitely 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.

But I will have to do more research about the adjuvant now that you bring it up.
I think this is a good idea and it was very helpful in my decision. In my case, I will never be getting another vaccine (for anything) because the risk/benefit analysis is against them (in my specific situation). I took the risk/benefit analysis very seriously and did not make the decision lightly. But I have not a shred of doubt that I have made the right decision.

My mcas doctor is pretty good but she's a bit dismissive of concerns around vaccine reactions so idk about asking her about that. But maybe with. Evusheld she can explain it
I 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).

exactly what you're saying, yes. Its a combo of two mab drugs, just like regeneron is, and all mabs seem to be *somewhat * long lasting already but not long lasting enough to be prophylactic.
I will 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).

I'm trying to learn enough about evusheld and mabs in general to know whether to trust it since I don't have a doctor advising me on the details yet. And I've had doctors say things were safe and I still have bad reactions
I agree and will be curious what you find out.

I'm definitely not worried about anaphylaxis. I mean I'm generally at peace with d3ath (not in a suicidal way to be clear, just that I am religious and believe in an afterlife of some kind and my current life is not amazing, so I'm not afraid to pass on). However what really scares the heck out of me is becoming sicker long term. I'm right at the edge of what I can tolerate
I am sure that you already know this (and I don't want to take your thread off-track) but anaphylaxis is very serious but does not always kill someone. Someone could have anaphylaxis and their throat closes up and their brain is deprived of oxygen but they do not die and instead are left brain-dead or paralyzed. It is not something to mess around with and even though I have not had anaphylaxis since 2016, I carry an EpiPen in my purse and wear a Medic Alert bracelet 24/7.
 
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
was clear to me that vaccines with adjuvants create a longer & stronger immune response than vaccines without adjuvants because this is literally the purpose of why the adjuvants are added.
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...
 
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
am sure that you already know this (and I don't want to take your thread off-track) but anaphylaxis is very serious but does not always kill someone. Someone could have anaphylaxis and their throat closes up and their brain is deprived of oxygen but they do not die and instead are left brain-dead or paralyzed. It is not something to mess around with and even though I have not had anaphylaxis since 2016, I carry an EpiPen in my purse and wear a Medic Alert bracelet 24/7.
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. But you make a good point. I should update my medical alert bracelet. I have one for covid. I Also want to get a dnr. I already have a living will. Being brain damaged severely but living is terrifying. We should get epipen but it's expensive even with insurance.
 
Messages
4,306
Likes
4,916
Location
Vermont, school in Western MA
I've done a LOT of research re: the Covid vaccines, specifically in regard to autoimmunity and my own situation. From my research, and my discussions with multiple doctors (of different specialties), it was clear to me that vaccines with adjuvants create a longer & stronger immune response than vaccines without adjuvants because this is literally the purpose of why the adjuvants are added.

This is a separate and distinct issue from the technology or type of the vaccine (meaning mRNA vs. adenovirus vector vs. other types, etc). In addition, my research was specifically on autoimmunity and not on vaccine side effects or reactivity in the general population.



I definitely 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.



I think this is a good idea and it was very helpful in my decision. In my case, I will never be getting another vaccine (for anything) because the risk/benefit analysis is against them (in my specific situation). I took the risk/benefit analysis very seriously and did not make the decision lightly. But I have not a shred of doubt that I have made the right decision.



I 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).



I will 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).



I agree and will be curious what you find out.



I am sure that you already know this (and I don't want to take your thread off-track) but anaphylaxis is very serious but does not always kill someone. Someone could have anaphylaxis and their throat closes up and their brain is deprived of oxygen but they do not die and instead are left brain-dead or paralyzed. It is not something to mess around with and even though I have not had anaphylaxis since 2016, I carry an EpiPen in my purse and wear a Medic Alert bracelet 24/7.
Another thing to be terrified about oh no ...