MONOCLONAL ANTIBODY INFUSIONS TOO SOON? - CLL Support

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MONOCLONAL ANTIBODY INFUSIONS TOO SOON?

wizzard166 profile image
61 Replies

After I was exposed recently to a two year old who had symptoms and tested positive for COVID, I called the ER of a local hospital where I knew they would be willing to give me an Infusion of Monoclonal Antibodies. They brought me in and gave me a subsitute for the Regeneron, because they ran out of the Regeneron. What I got was what they referred to as an earlier version manufactured by a different company. I had not been tested back then, but I never got any symptoms.

My wife and I decided to take a driving trip to Washington DC, just to get away over Christmas and through New years. We left on December 24, stayed overnight in Fayetville on the 24th and checked in our hotel in Washington DC on the 25th. I had felt something funny in my throat the day before we left, but ignored it because it wasnt clearly a painful feeling. The first night in Washington it was worse and then the next day in Washington a head cold clearly emerged. Monday the cold got worse and we were able to buy a Rapid Test kit (really hard to find one), I tested Negative. Tuesday the cold continued and my Wife convinced me to cut our trip short and drive home. We got back last evening, and today my cold is almost gone.

My Question if anyone is knowledgeable enough to answer it is this: If I tested positive, would it have been too soon to try to get another infusion? I've read that they don't do infusions if you are beyond ten days of exposure or a positive test, and I don't understand that logic. Why wouldnt they give infusions if you are getting worse? Is there something dangerous about infusing a person with the Monoclonal Antibodies if the Covid infection has already taken hold? It makes no sense to me. In my case I didnt test positive, so I didnt seek out a place that might infuse me, but what would the situation have been. I would have been less than ten days, but would the fact I was recently infused have led to them rejecting me for another one?

I'm now passed that point, and getting better, but I am wondering now what to do if I test positive soon. Is there a reason why I shouldnt get another Monoclonal Infusion, if its within two months of my last one? Is there any guidance on how long we need to wait to get another infusion?

I like many of us on this site have blood tested for antibodies after the two vaccine shots, and showed 0 Antibody production. I'm now realizing that this new Variant Omicron could be the kiss of death for someone like me, and the darn thing is raging insanely everywhere. Those who produced antibodies are somewhat safe with Omicron because it isnt as dangerous as the Delta Variant, but for those of us who produce no antibodies (like me), I'm thinking my only hope is the Monoclonal Infusions. Is it for some reason potentially hazardous to get two Monoclonal infusions not so far apart?

Thanks for any input.

Carl

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61 Replies
GMa27 profile image
GMa27

Sorry about ur trip. Always worse when holiday time is involved.I don't know anything about timing of the monoclonal antibodies but know of CLLers who didn't get antibodies from vaccines so they got monoclonal antibody infusions. If they are the same then I can't see it being harmful since people get them when not sick.

Hope someone has more information.

🙏💕

SofiaDeo profile image
SofiaDeo

IDK if there have been any studies regarding a series of infusions. These drugs are very expensive, in short supply, and infusion reactions are possible. And since they are relatively new, no one has really good data to make decisions. You need large numbers of patients, to get good data for decisions. For example, from what I am reading here (US Covid 19 Treatment Guidelines), initial studies in hospitalized patients showed there wasn't a significant change in the death rate, and that's where the recommendation of "not used in hospitalized patients" came from. But that was early in the pandemic with Alpha, what's to say it may be different with Omicron? I don't think anyone really knows. IDK if there have been any studies on serial exposures or infections, maybe you can find something in this links' clinical data tab.

Maybe see if there's convalescent plasma available near you, that seems to be something you wouldn't have to find rationalization for, if you get exposed/ill again.

covid19treatmentguidelines....

wizzard166 profile image
wizzard166 in reply toSofiaDeo

Thanks Sofia

I guess the only reason then is that post hospitalization the benefits of Monoclonal Infusion are not significant enough to warrant its use. It works extremely well the earlier after exposure it is given, so moral of the story is get the infusion quickly after exposure or testing positive.

I've read that Monoclonal Antibody Infusion can last between two and eight months, which sounds something like the vaccine effectiveness period. Likely that is because of the frequent mutations of the virus; such that, after six months the virus is a whole new animal. Still as with the Omicron, having been vaccinated is resulting in being infected but having much less dangerous infections. I truly believe that is why Omicron is supposedly not as dangerous as Delta. It likely is just as dangerous, however a significant percentage of the population (at least the ones who can read) are vaccinated. The vaccinated ones are not protected from infection, but they handle the infection markedly better without deadly situations. Most hospital stays and people dying from Omicron are those who were not vaccinated. So hopefully my infusion will help prevent the Delta and earlier versions (if they are even around any more), and prevent serious illness if infected by Omicron.

My guess is I can go for another infusion after about two to three months, and I had no side effects or problems from my first infusion. I suspect that COVID is with us to stay, and we will battle the constantly changing variants as time goes on. With that said, if the logic presented here holds true, the hospitalization and death rates from COVID will constantly decrease over time.

Carl

bennevisplace profile image
bennevisplace

I wonder what it was you were given first time around. "An earlier version" of Regen-Cov (Regeneron) doesn't compute. When was this?

I'm not medically qualified and can't see what risk there would be in having a second monoclonal soon after the first. I hear they have stopped giving Regen-Cov where Omicron predominates. Based on lab studies sotrovimab seems to be effective but it's in short supply.

In clinical trials these monoclonal antibody treatments, also the new antivirals, were much more effective at preventing severe Covid if given early, preferably within 5 days of onset of symptoms.

wizzard166 profile image
wizzard166 in reply tobennevisplace

I was given Eli Lilly's infusion, which is fully explained here:bamandete.com While this combination came out before Regeneron, and one of our members below said it ended up no good with Delta, Regeneron has supposedly failed with Omicron. The Nurse in the ER at Boca Raton Regional Hospital, now part of Baptist of Miami, said they are finding it better with Omicron than Regeneron is.

Carl

bennevisplace profile image
bennevisplace in reply towizzard166

Interesting to hear the hospital nurse talking up Lilly's MAbs when in vitro neutralisation assays found both Regeneron's and Lilly's combos to be ineffective against Omicron:

Several highly neutralizing mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59) completely lost inhibitory activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (∼12-fold decrease, COV2-2196 and COV2-2130 combination) or minimally affected (S309).

S309 is sotrovimab from GSK-Vir. biorxiv.org/content/10.1101... Other studies have found similarly. Real world experience is what matters and I look forward to seeing the data, though it seems that where Omicron is rife sotrovimab is the only game in town.

newyork8 profile image
newyork8 in reply towizzard166

Evusheld works agsinst Omicron. You can maybe get it in Hollywood. Free. I got it 2 weeks ago.

Cgolen99 profile image
Cgolen99 in reply tobennevisplace

I watched a webinar on this and it had to do with how the antibodies attach to the spikes of the virus to prevent the spikes from attaching to the body. Once the spikes attach to the body/organs (lungs etc) then the monoclonal antibodies don't really work which is why they need to be given early. That was my understanding of what I was watching anyway.

Justasheet1 profile image
Justasheet1

Eli Lilly was making Bamlanivimab and etesevimab before Delta rendered it useless.

And I was told that after thirty days after given Regeneron, you’ve eligible for 1/2 dose infusion.

wizzard166 profile image
wizzard166 in reply toJustasheet1

I was given Eli Lilly's infusion, which is fully explained here:

bamandete.com While this combination came out before Regeneron, and one of our members below said it ended up no good with Delta, Regeneron has supposedly failed with Omicron. The Nurse in the ER at Boca Raton Regional Hospital, now part of Baptist of Miami, said they are finding it better with Omicron than Regeneron is.

Carl

Justasheet1 profile image
Justasheet1 in reply towizzard166

Carl,

Interesting 🤔; I haven’t seen that bamlanivamab mentioned at all lately. The US government rescinded the EUA best to my limited knowledge on this subject.

Jeff me

bennevisplace profile image
bennevisplace in reply toJustasheet1

Yes, EUA for bamlanivimab monotherapy was revoked in April, but EUA for the combination was not.

SeymourB profile image
SeymourB in reply towizzard166

I suspect the nurse's statement should be interpreted as an adjuvant to the placebo effect. 😉

Davidcara profile image
Davidcara

Ok, without reading all of the replies, let me give you my take on timing of monoclonal antibodies.

First of all, don’t know what antibodies you received, or what strain of covid you were exposed too. Certain monoclonals cover Delta better than others, just as certain monoclonals cover omicron better than others. Actually omicron is the variant that is not well covered by most of the monoclonals.

First five days are best for monoclonals to work. The monoclonals sit on the covid receptor site, not allowing the virus to infect you. So the longer you wait, the more receptor sites have been occupied by the covid virus. In CLL, it is thought, the process of the virus occupying the receptors sites is slower than in people with normal immune system. Because of this, monoclonals could help past the five day window. The problem is, convincing someone of this.

Typically, you are not going to get a second monoclonal infusion. If you receive an antibody infusion that is sensitive to the virus strain that you have been exposed too, either they are going to work or they are not going to work

Those antibodies are siting on covid receptor sites, so no reason for another infusion Unless, it is discovered that you did not get antibodies that are sensitive to the strain of covid that you were exposed to, and they now become available, then a second infusion might help But chances of all of that being figured out and happening are just about zero

Even though you cannot tell in certain parts of the USA, monoclonal antibodies are a scared, expensive resource that is in short supply. If you already received one infusion, without sound evidence that you would benefit from a second infusion, those antibodies would be saved for someone else who could benefit from them

If you were to be exposed again or test positive in the near future, the best thing to do would be to call your MD for advice, with call your MD in bold lettering

Since you had symptoms, but never tested positive, you probably just had a cold.

Stay safe, wear a mask, pray for antivirals and direct antibody injections. Oh, and Happy New Year.

guzzifan profile image
guzzifan in reply toDavidcara

David, I interpret your explanation as meaning that the MABs occupy ACE2 receptor sites on the host cells and prevent the virus from infecting them. But according to the reference below, the MABs bind to the receptor binding domain on the spike protein of the virus itself. This would seem to better explain why the various MABs work more or less effectively depending on the strain of virus (the conformation of the spike protein). Have I misunderstood you? covid19treatmentguidelines....

Cheers. -Jim.

Davidcara profile image
Davidcara in reply toguzzifan

I was trying to explain it in lay terms. I guess it could be said, that the monoclonals get in the way of attachment of the virus to the host human? But yes, without doing research it appears as though you are correct. The monoclonal antibodies are attaching to the covid receptor binding, which prevents attachment of the covid virus to the human cell. Thanks for the clarification guzzifan.

Antibody
Davidcara profile image
Davidcara in reply toDavidcara

It actually might be nice if someone would like to explain what is happening in this picture. I’m too tired, might tackle it tomorrow. Happy New Years everyone.

SofiaDeo profile image
SofiaDeo in reply toDavidcara

The green antibodies are attaching at various places on the red Covid virus. This means the red Covid places have a difficult time attaching to the white receptors on human cells. The green antibodies are physically blocking the red virus from being able to attach to the white human cell. If one has a high viral load (really high exposue, self reinfection, being around an infected person who is shedding virus into the air/on surfaces), one is more likely to become ill, even with the infusion. There's only so many green bits, and if there are overwhelming red virus parts, more of them will be able to attach to cells.

Which is why it's important to not only avoid exposure to Covid, but to prevent spread/self infection. Limiting time around potentially sick people, breathing their air, is one way. Changing that pillowcase of a sick person physically removes any virus one breathes out onto it, so it can't make its' way back in, touching the mouth/nose. Or picked up from a drinking glass, if the same glass is used for a week without cleaning it.

Davidcara profile image
Davidcara in reply toSofiaDeo

Thank You SofiaDeo

wizzard166 profile image
wizzard166 in reply toDavidcara

Thank you very much David for the added knowledge you have given me and others who are reading this thread.

I tested negative using a Rapid Test we found thank God in a lower income section of Washington DC. Every other CVS or Walgreens we drove to or called, and that is over twenty, closer to where we stayed near the White House, had been empty of test kits for a week already. One of the managers of a CVS suggested driving into a bad area, where he said the chance of finding a kit was much greater, ended up working out for us. The thing is I don't know how accurate a negative reading was with a Rapid Test kit.

Really interesting thing is something I read a few days ago on the web. It had to do with a new finding on one symptom with Omicron, which is not found with the other COVID Variants. It is DRENCHING NIGHT SWEATS. How ironic that this is one of the symptoms we have with our CLL. I thought i was over what was believed to be a bad cold yesterday after six to seven days that started with a sore throat. Then last night I had a Drenching Night Sweat and this morning I'm coughing again. Still I feel that I've turned the corner, and hopefully the coughing is just old stuff from the cold finally coming up.

I've been asking the question about ability to get more infusions, not because of this current episode; instead, I'm thinking ahead to the next scare I'll have. Lets face it COVID is not and will not be going away; it is here with us for the long term without a question. It mutates hourly and the pharmaceutical combinations such as I had or the Regeneron, as well as the vaccines developed to date, will lose effectiveness against some of the new variants. With vaccines being useless for me, and an immunologist said she found evidence that antibody levels for older vaccines we all have had in prior years are at way too low levels in my blood stream, I feel my only hope to survive are either the infusions or the new pills Pfizer and Merck are developing. I was just wondering if I get a new infection in the next few weeks, if a second infusion (maybe Regeneron this time) would be dangerous to me.

By the way, as I added to a reply above this post, I had Eli Lilly's BAMLANIVIMAB 700 AND ETESEVIMAB 700 20 ML INFUSION.

Carl

Davidcara profile image
Davidcara in reply towizzard166

I’m definitely no expert, just voicing my own opinions from what I believe to be correct, or at least has the potential to be correct. Such a new changing virus, the information is always being updated, and not always agreed upon by the real experts. I think down the road, if you were to become infected or, had a significant exposure you should ask your MD about another round of monoclonal antibodies. Especially if it is felt you were exposed to omicron, and the hard to find omicron sensitive Sotrovimab monoclonals are available.

I personally like the Binax now home covid test. I think if you get a good sample from the nasal swab, that is half the battle for an accurate result. Have had luck finding them on Walmart online, for pick up

I’m just trying to be careful, which is pretty much all I can do at this point. I absolutely love my oncologist, he is not listed as a CLL expert but, he is an amazing smart and thoughtful person. Who in addition, did not mind one bit when I went for a second opinion at the beginning of this journey.

I’m hoping for more antiviral pills to be easily available, for folks like us who might need them.

Also cannot wait for Evusheld. In the USA we received 50,000 treatments. At least I think it is 50,000 treatments. One treatment is two doses, given one right after the other. California received 5000 doses or treatments, whatever it may be??? Hope to eventually get one treatment. My oncologist referred me to whoever is overseeing this for the healthcare system that I am a member of, Kaiser.

5000 for all of California right now is not much, but I am frequently checking my email, and trying to answer all phone calls.

Anyways, for whoever has read these post, hope they are not to boring. Kind of therapeutic, I guess.

You all of a healthy and safe New Year.

newyork8 profile image
newyork8 in reply toDavidcara

The MABs wear off/degrade which is why you need fresh ones. I had Regeneron and that may protect up to 8 mos. Now I got Evusheld which should protect for 6 months. So I have four different MABs in my system. The more the merrier. I have had 4 vaccines...no effect.

SeymourB profile image
SeymourB in reply tonewyork8

newyork8 -

My understanding is that REGEN-COV has detecatable MABs at 6 months, but how much they protect at that time and against what level of disease is highly debatable. The actual trials were much shorter duration, and against earlier variants.

Evusheld, on the other hand, was specifically designed to last and maintain effectiveness longer against death and hospitalization due to variants. Since there's only been 6 months or so of Evusheld patient data, that's the number often cited. It certainly lasts longer than that. But we shall see what variants the future holds.

I think that we have to demand that press and government cease the unqualified use of words like "protection" or "effective". We always need to know against what level of disease, and agains what variant. It makes for much longer headlines, which are understandably harder to digest. But it prevents disillusionment and despair due to misunderstanding.

=seymour=

wizzard166 profile image
wizzard166 in reply toSeymourB

Thanks Sy

I have to find out if I can get Evusheld. I'm in Lake

Worth FL, and I'll report here on whatever I find out.

Carl

newyork8 profile image
newyork8 in reply toSeymourB

Regeneron claims 8 mos protection with 81% reduction in infection. Not peer reviewed. Question. .why isn't the US govt mass producing MABs? Also there is no FDA commissioner and head of HHS missing in action. Easy to criticize but when those in charge fail they should be held accountable.

SeymourB profile image
SeymourB in reply tonewyork8

newyork8 -

If REGEN-COV was ever 80% effective, it was probably against death due to the original variant. I don't think any therapeutic blocks infection completely. Everyone still gets at least an asymptomatic infection unless they mask and distance carefully.

As the virus has mutated, REGEN-COV has been less and less effective against death, serious illness, and symptoms. It also loses effectiveness with time since infusion, because it gets filtered out by the liver and spleen. So not much is left from the original dose after months. The original hope was to maintain stated effectiveness percentages a month after infusion. All after that was bonus.

What ticks me off is the failure at state and hospital level to clearly implement priority for our population. They knew Sotrovimab was coming, and new it was intended for the riskiest patients, but never did the basic clerical and computer work, at least not here in Louisiana.

So I think it starts with state public health, which is already meeting with hospitals at least weekly

here.

Now, the issue is holidays and sick days among healthcare workers, since breakthrough infections may be mild in boosted workers, but they still happen.

Plus, the state of

Louisiana has not closed schools or mandated online classes, and doesn't have enough rapid tests for the surge, which starts on Tuesday. Even if they mask in the classroom, transmission happens in the lunchroom. My wife teaches 8th grade.

=seymour=

newyork8 profile image
newyork8 in reply toSeymourB

Regeneron not effective re omicron but delta still out there. CDC miscalculated amount of omicron. Lower vs delta then 1st reported.

wizzard166 profile image
wizzard166 in reply tonewyork8

Hey New York

Thank you for the input. If you have had four and no bad side effects, then I feel alot safer with trying some more. Sounds like this Evusheld is a winner with Omicron, so I'll begin to look into that one.

Carl

LeoPa profile image
LeoPa

Based on what I read so far monoclonal cocktails are less efficient against omicron because it has a great capability of escaping antibodies. But t cell based immunity is very efficient against it. Therefore even if your vaccines produced zero antibodies they should provide you with some t cell based immunity against omicron. Monoclonals were shown to last up to 6 months in the blood. At one moment they seemed like the solution for those who cannot produce antibodies. But that changed with omicron. Sotrovimab and Evusheld are the only partially efficient ones against it

Davidcara profile image
Davidcara in reply toLeoPa

You know how you see those car stickers that say Baby On Board, would love to be able to say Evusheld On Board.

LeoPa profile image
LeoPa in reply toDavidcara

I'd be glad to have paxlovid in the cupboard ☺️

newyork8 profile image
newyork8 in reply toLeoPa

DANGER...Paxlovid with Ibrutinib, etc. not advised. Do your research please if you are on the BTK inhibitors.

LeoPa profile image
LeoPa in reply tonewyork8

As far as I know it's a 4 day course. It should not be a problem to stop the brutinibs for that long but always check with your doctor of course.

mikec11 profile image
mikec11

I’m in Florida and SARS-CoV2 is huge again. Influenza is starting a similar tract as 2018-2019. Rhinovirus has been very active. So if it was a “cold” or a mild COVID-19 it’s been inconsequential for you, Thank God! Rapid tests are tricky with Omicron. When you test positive, you are positive. When you test negative you can’t rule it out. Especially with one test.

I had a very similar “cold” that tested negative even as it developed into a moderate sinus headcold and my second Rapid Test was also negative.

My plan going forward is continue rapid testing if I get sick and based on signs and symptoms retest often, go to a drive through to cross check my home tests and if I’m not getting clarity within 2-3 days hopefully get monoclonal abs. If I get severe enough head to the ER and deal with whatever grief I’m given by the staff.

Right now I’m self-isolating until the surge passes. The biggest threat to us is poor healthcare by burned out healthcare workers who blame the patient for contributing to their stress.

Stay safe and Happy Newyear

Davidcara profile image
Davidcara in reply tomikec11

Appreciate your input mikec11. I do think the healthcare workers are not blaming people like me and you. I think, just like many people, the healthcare workers are blaming the unvaccinated.

You stay safe and Have New Year too!

SofiaDeo profile image
SofiaDeo in reply toDavidcara

If I were still working, I would be really, really upset at all the unvaccinated. And it may have driven early retirement, unfortunately continuing to the staff shortage. My feelings are, if these people don't care, I am not risking my life. I bet a number of those who quit feel the same.

Similar to the airline personnel problems causing flight disruptions; I was reading how the overtime hours that many staff usually accept are now being refused due to violet passengers. So the projected staffing needs that historically count on overtime acceptance, didn't happen. I am sure it's the same in hospitals.

wizzard166 profile image
wizzard166 in reply tomikec11

Hey Mike

Yea I did worry about the possibility of a false negative, but I didnt follow up with a regular PCR. I felt I was improving daily and decided it wouldnt matter even if I tested positive on a second test. Trouble with me is I've been fooled too many times in the past, when I believed I had beaten a cold that hung with for a week or so; then, all of a sudden it revives and goes down lower into my chest. Three times this has resulted in me ending up in an ER and then into a hospital bed with Pneumonia. I finally got wise about four years ago, and if I hadnt beaten one in four days I called my Dr and got an antibiotic. Now I've not had Pneumonia since January 2016. This time I didnt try to see a physician, because I had just had the infusion and figured I'd be safe from a more serious illness. We'll see.

I felt much safer in Washington than here in Florida, and ten times safer in New York City last September than here in FL. What it comes down to is that in NYC you couldnt go into a restaurant, never mind other places like Theatres, without showing proof of vaccination accompanied by a picture ID. Then I felt totally safe sitting with people all around me, knowing I was protected by the Herd. Back around home in FL so few people wear a mask, and you can go anywhere with no proof of vaccination. In Boston, where I go every six months to see my CLL Specialist, everyone even walking in the streets has a mask on (and I really mean everyone).

Carl

mikec11 profile image
mikec11

Very wise actions you take. My last pneumonia was from RSV at the start of the pandemic. I also go to Boston every year and trust my Specialist at Dana Farber.

wizzard166 profile image
wizzard166 in reply tomikec11

Hey Mike happy to hear you agree with me.

SeymourB profile image
SeymourB

wizzard166 -

I think that antibodies from previous infections, boosted vaccines, and MABs have a harder time with Omicron. Even if an antibody does not neutralize, it still may help reduce virus particle count. Many of us with CLL (maybe half?) still have CD8 T-cells that help, too. So I'm cautiously optimistic about Omicron. The catch is that it spreads so quickly, and could knock some of us for a loop if we have comorbidities. Thankfully, it doesn't seem to infect lung cells nearly as much, and doesn't seem to cause as much immune system overload like earlier variants.

A preprint from Scotland investigates why Omicron does not cause lung trauma, evades many (but not all) existing antibodies from previous infection, vaccines, and MABs:

gla.ac.uk/media/Media_82936...

The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism

They conclude that it's because Omicron no longer relies on the ACE2 receptor and TMPRSS2 (TransMembrane Serine Protease 2) that are found in such abundance in lungs. Instead, it relies on old fashioned coronavirus "endosomal fusion."

"Conclusions

The Omicron variant represents a major change in biological function and antigenicity of SARS-CoV-2 virus. In this study, we demonstrate substantial immune escape of this variant with clear evidence of vaccine failure in dual vaccinated individuals and partial restoration of immunity following a third booster dose of mRNA vaccine. In addition, we demonstrate a shift in the SARS-CoV-2 entry pathway from cell surface fusion, triggered by TMPRSS2, to cathepsin-dependent fusion within the endosome. This fundamental biological shift may affect the pathogenesis and severity of disease and requires further evaluation in population-based studies."

TMPRSS2 is an enzyme in our cells that goes to work after the SARS-CoV-2 spike protein binds with the ACE2 receptor that is found mostly (but not exclusively) in our lung cells.

Cathepsins are standard enzymes that split up proteins inside our cells, and are part of our innate cellular immune defense.

So Omicron is really different - and not just due to the spike protein mutations as in past variants. It's like a hybrid with earlier coronaviruses.

I'd like to be one of the first people in 2022 to say that Omicron does not cause the symptoms that we call COVID-19. I still want some Evusheld, because Omicron will probably not be the last variant.

Also, we need to be on the lookout for why the few people who have died from Omicron actually died. Counts from England as of Friday were only 75 deaths, with 981 hospitalizations, and about a half million cases of Omicron. I'm also curious to hear about simultaneous Omicron and influenza infections.

assets.publishing.service.g...

I think the bigger problem with Omicron is the surge it causes on hospitals, and the resulting denial of service for other illnesses. So, let's be careful walking on ice, please. And in the US, Delta is still spreading in some states as well. It would be a real shame to relax because of what we hear about Omicron, and then catch a case of Delta.

=seymour=

SofiaDeo profile image
SofiaDeo in reply toSeymourB

My understanding is that well over 99% of omicron deaths are in the unvaccinated; even without affecting ACE inhibitors I think it may play out to be the virus itself, much like the Alpha variant. Viral load may indeed be the reason behind the deaths. And the only way unvaccinated folks can really significantly reduce viral load, is to vaccinate.

AussieNeil profile image
AussieNeilPartnerAdministrator in reply toSofiaDeo

SofiaDeo, I can see US media reports stating 99% of Omicron deaths being in unvaccinated folk. That's remarkable, given concerns that vaccinations may be less protective against the Omicron variant and that in the US, about 74% have had one vaccination and about 63% have had two vaccinations. See:

mayoclinic.org/coronavirus-...

usafacts.org/visualizations...

The sources below don't report as high a percentage in favour of being vaccinated, but there is still a huge discrepancy.

ourworldindata.org/covid-de...

ons.gov.uk/peoplepopulation...

Perhaps this will finally convince the vaccine hesitant to be vaccinated, but in leaving vaccination so late, they will be facing most of the Omicron wave without much in the way of vaccination protection.

Neil

newyork8 profile image
newyork8 in reply toAussieNeil

Is it not the case that fully vaccinated (2 doses) people are getting Omicron? I know personally 6 of them. Now people need a booster which wanes after 10 weeks, right? Prior infection with Alpha and Delta doesn't protect much right? I know 3 of those people. Omicron is not nearly as serious as Delta right? So maybe it's better that everyone gets omicron and we finally get some herd immunity? Or will it be like the flu, lots of people get the flu and lots die from it every year and the world doesn't stop for that. We CLL patients don't get a positive immune system vaccine reaction for flu or pneumonia either right? Nothing new there. Now why don't the governments crank out loads of Evusheld and Strov and give everyone immunity? Seems to me that's the solution for even us. The hesitant should not have as big a problem with MABs. I've had 4 vaccines and Regeneron and Evusheld. But I have no protection for flu and pneumonia even though fully vaccinated for those. The key is also treatments ...Remdesivir....steroids, etc.

AussieNeil profile image
AussieNeilPartnerAdministrator in reply tonewyork8

The issue is that you can't quickly "crank out loads of" monoclonal antibodies. It's a classic critical path problem you see in production, usually illustrated by comparing it with giving birth, which takes 9 months for one woman, but you can't reduce it to 3 months by giving the task to three women.

Neil

newyork8 profile image
newyork8 in reply toAussieNeil

Curious if Evusheld is at maximum production. Can new plants be created if massive resources are applied?

AussieNeil profile image
AussieNeilPartnerAdministrator in reply tonewyork8

I don't think you appreciate the problem with biological processes. Your ability to speed them up is constrained by multiple factors, which I'm sure have all been optimised for high yield with a short production cycle. Companies hate inventory; you have to fund the production and only get your return on your investment when it is produced and sold. If it takes 2 months to make a batch of monoclonal antibodies, if you build 100 plants (which can take months too to build and then get them up and running smoothly), eventually you'd get 100 times the production. It still takes two months to make a batch, by which time we could well have another variant for which you now have a massive quantity of rather expensive product which may not work that well.

newyork8 profile image
newyork8 in reply toAussieNeil

No I don't appreciate the problem very well. But are you confident the governments around the world have devoted sufficient resources to ramping up production when our US govt can't even get testing supplies out? I wonder has the same fiscal effort been apllied to MABs as to the vaccine itself? They said it takes 10 years to create a vaccine--wrong. Would you rather have an effective MAB or an effective vaccine. The vaccines are getting beat by the virus as well. But the MABs solve the problems of the immunocompromised which are the ones most at risk for hospitalization and death. The vaccines are of much less benefit. The death rate for healthy sub 70 year olds is less than 1%. And sub 50 much lower and we wonder why healthy young people are hesitant.

AussieNeil profile image
AussieNeilPartnerAdministrator in reply tonewyork8

Sure we can do much better! It's becoming impossible to get RAT tests in Australia and PCR test times are stretching out so long that you risk going past the treatment window. That's if you can even get access to monoclonal antibodies or antivirals! I face a 6 hour drive to get access to either, IF there's a hospital bed when I get there. Of relevance, those hospital beds are more likely to be free if those with competent immune systems would get vaccinated!

It shouldn't be a choice between an effective MAB or an effective vaccine. We need both! Just bear in mind that for the same cost of protecting one patient with an infusion, you can protect around ten times as many by vaccination, without tying up constrained hospital resources. The challenge is that both vaccines and MABs require a long time to develop, test and manufacture. That's a recipe for disaster, because the further you look ahead, the less accurate your predictions. The standard way of compensating for invariant production times is to do production in parallel with the approval trials, just as we did with vaccines. That unfortunately means you have to underwrite the risks of producing products you may never use.

Don't forget that a large part of why we are in our current situation, is because we are trying to navigate the challenge of keeping our economies running while attempting to save lives. That's playing out in an environment with extremely long supply chains, because most economies outsourced their manufacturing to provide lower prices.

Neil

Justasheet1 profile image
Justasheet1 in reply toSofiaDeo

Sofia,

“And the only way unvaccinated folks can really significantly reduce viral load, is to vaccinate.”

Or have a Doc write you a Rx for something you and I need greatly.

Jeff

SofiaDeo profile image
SofiaDeo in reply toJustasheet1

Well, the drugs are really expensive (not just cost of manufacture, but staffing/administration as well(, and have their own side effects. People with comorbities on a number of other meds are going to have contraindications taking ritonavir, and need much more monitoring with possible hospitalization from side effects in this group. Plus I have concerns as I see people here have difficulty accessing the various meds to begin with.

SeymourB, I am not sure it's a red herring. Of course as a population gets vaccinated the hospitalizations will have mostly vaccinated folk, but it seems the death rate is very different between the groups (vaccinated vs. unvaccinated). And disregarding the death rate, hospitals are overwhelmed. We're happily not seeing the deaths we were with Alpha, but it's still a strain on resources & affecting staff as well as the ability to care for medical problems other than Covid.

It is to be expected that even in vaccinated groups, there will be more mortality in the subset of very young /older/comorbidities, like exists with influenza. If you read about the 1957-58 influenza, the deaths were mostly limited to these age groups because adults vaccinated. In 2009, the "swine flu" vaccine couldn't be made fast enough before the virus peaked. But swine flu wasn't as transmissible/deadly.

weather.com/health/cold-flu...

It's just mind boggling to me that we have the tech and know-how to clamp down on these much more virulent, transmissive strains, and people in the US won't vaccinate.

SeymourB profile image
SeymourB in reply toSofiaDeo

SofiaDeo -

I think that vaccination status vs death is a red herring, since if 100% of the population is vaccinated, whatever deaths will be in vaccinated people. What we need, and what we lack are comparisons of absolute numbers of vaccinated vs unvacccinated people by age group to compare with deaths in vaccinated and unvaccinated population so that we can calculate risk. The UK data comes close to providing this info, but does not come out and calculate a risk yet.

The latest UK Omicorn data indicates that 73 to 80% of hospitalized Omicron cases in England are vaccinated to some degree:

assets.publishing.service.g...

That's understandable, since the majority of the population has had at least one dose.

I looked further for more detailed stats, and found:

assets.publishing.service.g...

See p36 and ff for statistic on vaccine status vs hospitalization and death by age group and number of doses.

A footnote on p37 says:

"In the context of very high vaccine coverage in the population, even with a highly effective vaccine, it is expected that a large proportion of cases, hospitalisations and deaths would occur in vaccinated individuals, simply because a larger proportion of the population are vaccinated than unvaccinated and no vaccine is 100% effective. This is especially true because vaccination has been prioritised in individuals who are more susceptible or more at risk of severe disease. Individuals in risk groups may also be more at risk of hospitalisation or death due to non-COVID-19 causes, and thus may be hospitalised or die with COVID-19 rather than because of COVID-19."

P38 gives us: Table 10. COVID-19 deaths (a) within 28 days and (b) within 60 days of positive specimen or with COVID-19 reported on death certificate, by vaccination status between week 47 and week 50 2021

We see that more deaths are in vaccinated than unvaccinated, and this increases with age. Again, this is due to more vaccinations in older groups.

I should add that week 47 to 50 may have still had some Delta, although Delta has since declined rapidly.

Hence, I still would like to see an anlysis of primary and secondary cause of death in Omicron cases, especially Omicron vaccinated cases.

=seymour=

wizzard166 profile image
wizzard166 in reply toSofiaDeo

Sofia ( I do realize this is not your name)

I just saw the Governor of Maryland (Hogan) in an interview with Dana on CNN this Morning. He said: " 92% of all Maryland Hospitalizations since Omicron were people who WERE NOT VACCINATED. He went on to say that it is incredible that segments of our population believe the lies that have been spread against masks and vaccines, but he said it is what it is and we need to be aware of the dangers of the unvaccinated.

This is exactly what I was alluding to earlier in my Post that started this whole string. I didn't exactly knock the lies spread in states such as my own, but instead I praised the situation in New York and Boston. In New York you cannot enter any restaurant, even the small ones on side streets, without showing a Vaccination Card and Photo ID. Of course you can't go into a theatre or a Play without the same. Prior to the onset of Omicron I went to a Play on Broadway and ate in Tavern on the Green in Central Park, went to smaller restaurants, and stayed in a nice hotel near Central Park. I loved life and doing those things, and I never got ill, and I know I was protected by the Herd around me from COVID. Now with Omicron I realize it is totally different, as Seymour fully explained just prior to Sofia's reply, and I know the Herd can't protect me right now. I wish that in my Home State of Florida things were very different, but it is what it is.

Carl

SeymourB profile image
SeymourB in reply towizzard166

wizzard166 -

Is this the CNN segment?

cnn.com/videos/politics/202...

AT 4:15 he said that 92% of the state is vaccinated - not necessarily fully vaccinated, or boosted, BTW. He went on to say that 8% of the state's unvaccinated people are responsible for 75% of people filling COVID beds. That leaves 25% of COVID beds having some vaccination.

I say all this because overstating the case for vaccination plays into antivaxxer sentiment. Vaccination does not provide sterilizing immunity (immunity that prevents infection), and some vaccinated people will surely die. There will be a story for each case involving comorbidities, I am certain. Antivaxxers love to deal in absolutes. Vaccination is not an absolute thing - especially not with Omicron.

To properly assess the protection given by vaccination, scientists must compare at least 2 population groups - a jurisdiction that's largely unvaccinated with one that is highly vaccinated. Then they must do arithmetic to observe the symptom, hospitalization, or death rate in the 2 groups. This has been done for all previous variants, and the UK data is beginning to show it for Omicron. The key observation is that single and double dose are not that protective for Omicron - a boost is needed. Even so, Omicron does not appear to be that deadly overall - vaxxed or not. But we have no data on various levels and types immune compromise.

We cannot do a simple survey of a given hospital and extract meaningful data from how many people at that hospital are vaccinated or not. As I said before, even if everyone is vaxxed and boosted, there will still be deaths due to SARS-COV-2 infection. The difference is that there will be fewer deaths than in a comparable unvaccinated group.

=seymour=

wizzard166 profile image
wizzard166 in reply toSeymourB

Hey Sy

Really good information and analysis. I particularly love the following, which is what I was trying to say in my post:

He went on to say that 8% of the state's unvaccinated people are responsible for 75% of people filling COVID beds

When a prior reply to my post was referencing that most of the hospitalizations would be from vaccinated people, it did reference that was because a greater percentage of the group in question had been vaccinated already. What I was trying to say in simple analytical terms is that the truly valid analysis would compare percent of hospitalized of unvaccinated versus percent of those hospitalized of the already vaccinated. The sentence I'm highlighting above from your reply points this out in Spades. 8% of unvaccinated resulted in 75% of hospitalizations. That means that almost ten times the number of hospitalizations are from unvaccinated people.

Carl

Justasheet1 profile image
Justasheet1

NY,

No it’s not.

ncbi.nlm.nih.gov/pmc/articl...

“The half-life of ibrutinib is 4 to 6 hours and the drug does not accumulate after repeated oral dosing.[48].

Metabolism: Primarily through CYP3A. Active dihydrodiol metabolite. DDIs with mod...

Absorption: Median Tmax 1–2 hrs. Steady state AUC at 420 mg/d dose = 680 ± 517 ...

Distribution: 97.3% plasma protein bound in vitro (reversible). Vd at steady state 683 L

Elimination: Mainly as metabolites via feces; high first-pass effect. Half-life 4 to 6 hours”

Jeff

newyork8 profile image
newyork8 in reply toJustasheet1

I stand corrected as to half life...thanks. However, the effects of Ibrutinib on our system does not clear for 7 days or so. So one should find out the interaction of these new covid treatments to determine how or even whether it is safe for us on BTK inhibitors to take them. Can we stop Ibr take the pill, and then start Ibr again? I worry many prescribers of the pill won't check interactions.

AussieNeil profile image
AussieNeilPartnerAdministrator in reply tonewyork8

The issue with the interaction of any drugs (like ibrutinib) that rely on CYP3A for clearance, is that CYP3A inhibitors slow the rate of clearance from your body after you take the drug. Thus the drug blood serum level stays elevated for longer, increasing the risk of side effects. The standard management approach is to reduce the interacting drug dose to compensate.

See the Imbruvica Prescribing Information section 2.3 Dosage Modifications for Use with CYP3A Inhibitors at imbruvica.com/files/prescri...

The version states at the moment!

Coadministered Drug Recommended IMBRUVICA Dosage

B-Cell Malignancies

Moderate CYP3A inhibitor

280 mg once daily

Modify dose as recommended [see

Dosage and Administration (2.2)]

Then there's a table entry for a few drugs, then finally:-

• Other strong CYP3A inhibitors

Avoid concomitant use.

If these inhibitors will be used short￾term (such as anti-infectives for seven

days or less), interrupt IMBRUVICA.

Neil

PS You can correct your half life statement by selecting 'More v' below your reply and then selecting 'Edit'.

newyork8 profile image
newyork8 in reply toAussieNeil

So is that the issue with Paxlovid?

AussieNeil profile image
AussieNeilPartnerAdministrator in reply tonewyork8

Yes, per: fda.gov/media/155071/download

Risk of Serious Adverse Reactions Due to Drug Interactions:

Use of PAXLOVID, a CYP3A inhibitor, in patients receiving concomitant medications

metabolized by CYP3A may increase the plasma concentrations of those concomitant

medications.

Use of concomitant medications that inhibit or induce CYP3A may increase or decrease

concentrations of PAXLOVID, respectively.

These interactions may lead to:

• Clinically significant adverse reactions, potentially leading to severe, life-threatening, or

fatal events from greater exposures of concomitant medications.

• Clinically significant adverse reactions from greater exposures of PAXLOVID.

• Loss of therapeutic effect of PAXLOVID and possible development of viral resistance.

SofiaDeo profile image
SofiaDeo in reply toAussieNeil

And the ritonovir part of Paxlovid, which causes the problems, is necessary to get high enough blood levels of the other agent, which is the one that affects the Covid virus.

newyork8 profile image
newyork8 in reply toAussieNeil

Sounds like bad stuff! I'll pass.

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