Coronavirus

[bkp_duke]

Got it. Agreed. So the boost improves the breadth. Should have stuck with that! This is why the booster is so good and of crucial importance. (And I guess “existing antibodies” includes those in the germinal centers that are really not amplified until the boost?)

Well, that's not how we define "breadth" in Immunology. Breadth = number of unique antibody epitopes. The number of antibodies increases, but the number of unique antibody epitopes does not.

 

[AlanSubie4Life]

The number of antibodies increases,

I see. I was just meaning the number of antibodies with unique structures when referring to “breadth.” The number of different antibodies increases and the quantity of each different type increase with the boost, as I understand it (caveat that with they may all have technically “existed” before the boost, but haven’t been boosted yet (and are really not very useful upon infection as a result) because they arose through somatic hypermutation as much as 3-4 months after the second dose, when the body would not have been churning out massive numbers of those antibodies). Is that reasonably close to correct?

 

[bkp_duke]

I see. I was just meaning the number of antibodies with unique structures when referring to “breadth.” The number of different antibodies increases and the quantity of each different type increase with the boost, as I understand it (caveat that with they may all have technically “existed” before the boost, but haven’t been boosted yet (and are really not very useful upon infection as a result) because they arose through somatic hypermutation as much as 3-4 months after the second dose, when the body would not have been churning out massive numbers of those antibodies). Is that reasonably close to correct?

I'm too busy to draw this, so I hope the verbal description works below:

Wuhan strain Vaccine - think of 1000 "possible" antibody epitopes. First dose generates robust response to say 700, booster second shot then gives you more of the first 700, and you see antibodies to 100 additional epitopes (800 total). 3rd shot, you get up to 850 total (starting to taper off). You are filling in sides of the bell curve, but you never get to the full 1000 (random number I picked to make stats easy).

Now, with the Omicron variant, of the THEORETICAL 1000 antibodies from the first show, only say 60% will even bind to the S-protein from Omicron. So that original 700 that could react to Wuhan, only 420 can react to Omicron (0.6 x 700). Second shot, you are up to 480, and after the third you are at 540. You are still protected, but there are holes in the next, so to speak.


Now, imagine instead you are boosting with an Omicron-specific booster. You have the first 800 unique epitopes on board from the first 2 shots, but now you have say 500 MORE epitopes that the Omicron-specific booster can bring (500 independent of the first 1000). Lets say you get the same efficacy from the omicron-specific shot as your first show (this is a low estimate, it's probably higher) and get 70% of the possible epitopes. That's 350. 350+800 = 1150 unique epitopes.

The second scenario obviously gives you a much "broader" response with many more 3D protein epitopes covered than just keeping using the same booster. This is basically how your annual influenza vaccine works (but with 4 variants in one shot, and with some "bleed off" from last year's booster because it wanes).

Hope that makes sense.

 

[AlanSubie4Life]

I'm too busy to draw this, so I hope the verbal description works below:

Wuhan strain Vaccine - think of 1000 "possible" antibody epitopes. First dose generates robust response to say 700, booster second shot then gives you more of the first 700, and you see antibodies to 100 additional epitopes (800 total). 3rd shot, you get up to 850 total (starting to taper off). You are filling in sides of the bell curve, but you never get to the full 1000 (random number I picked to make stats easy).

Now, with the Omicron variant, of the THEORETICAL 1000 antibodies from the first show, only say 60% will even bind to the S-protein from Omicron. So that original 700 that could react to Wuhan, only 420 can react to Omicron (0.6 x 700). Second shot, you are up to 480, and after the third you are at 540. You are still protected, but there are holes in the next, so to speak.


Now, imagine instead you are boosting with an Omicron-specific booster. You have the first 800 unique epitopes on board from the first 2 shots, but now you have say 500 MORE epitopes that the Omicron-specific booster can bring (500 independent of the first 1000). Lets say you get the same efficacy from the omicron-specific shot as your first show (this is a low estimate, it's probably higher) and get 70% of the possible epitopes. That's 350. 350+800 = 1150 unique epitopes.

The second scenario obviously gives you a much "broader" response with many more 3D protein epitopes covered than just keeping using the same booster. This is basically how your annual influenza vaccine works (but with 4 variants in one shot, and with some "bleed off" from last year's booster because it wanes).

Hope that makes sense.

Yep, understood, that's how I understood it, essentially. Sorry for the confusion.

And we could fill in more of this hypothetical and show that the Omicron shot alone (not layered on natural immunity or prior vaccination) provides quite poor cross-neutralization of prior variants (very few of the 500 (or more, maybe it is 1000 total) Omicron booster epitopes elicit antibodies binding to prior variants ). These prior variants could re-emerge, potentially, especially if not suppressed with additional immunity.

(This image annoyingly doesn't provide the x-axis, that's for WT or something (have to go to the tweet and click on the paper), so poor cross-neutralization.)

Coronavirus

Wearing a mask (make it an N95, folks, it’s easy and they are more comfortable) might be good even if you get infected. Aside from the benefit of reducing infection. The minimum infectious dose model of infection seems to really be a thing…...

teslamotorsclub.com

 

[AlanSubie4Life]

I'm too busy to draw this, so I hope the verbal description works below:

Wuhan strain Vaccine - think of 1000 "possible" antibody epitopes. First dose generates robust response to say 700, booster second shot then gives you more of the first 700, and you see antibodies to 100 additional epitopes (800 total). 3rd shot, you get up to 850 total (starting to taper off). You are filling in sides of the bell curve, but you never get to the full 1000 (random number I picked to make stats easy).

Now, with the Omicron variant, of the THEORETICAL 1000 antibodies from the first show, only say 60% will even bind to the S-protein from Omicron. So that original 700 that could react to Wuhan, only 420 can react to Omicron (0.6 x 700). Second shot, you are up to 480, and after the third you are at 540. You are still protected, but there are holes in the next, so to speak.


Now, imagine instead you are boosting with an Omicron-specific booster. You have the first 800 unique epitopes on board from the first 2 shots, but now you have say 500 MORE epitopes that the Omicron-specific booster can bring (500 independent of the first 1000). Lets say you get the same efficacy from the omicron-specific shot as your first show (this is a low estimate, it's probably higher) and get 70% of the possible epitopes. That's 350. 350+800 = 1150 unique epitopes.

The second scenario obviously gives you a much "broader" response with many more 3D protein epitopes covered than just keeping using the same booster. This is basically how your annual influenza vaccine works (but with 4 variants in one shot, and with some "bleed off" from last year's booster because it wanes).

Hope that makes sense.

Reflecting this general simplified framework, a simple summary of how neutralization looks with “booster” infection by BA.1 vs. boosted vaccine, vs. BA.4/5. Obviously this is not protection against severe disease; that’s a somewhat less correlated metric (lots of non-neutralizing epitopes!). Looks like about 3x less neutralization of BA.4/5 vs 2x less of BA.2.

Note this is also not representative of protection with just prior infections (no vaccination) - that’s worse, unless perhaps you’ve been infected 2 or 3 times previously. (Seems not worth it!)

Seems like this makes it likely that BA.4/5 could spread widely in the US and become dominant, but I guess we’ll see how the overall immunity picture works out (could be another variant that takes over too!).

Very glad to have got my second booster; can just wait for better coverage later, seems like it’ll be another 5-6 months; perfect timing. Guess I’ll be sticking with that N95 for another 5-6 months.

We have to hope there isn’t another jump from Omicron of course (some models estimate 30% chance per year).

https://twitter.com/x/status/1529099593832468481

 

[bkp_duke]

Youngest went back to school today, finally had a negative antigen test. No one else has gotten sick in the family, and we didn't take any precautions.

It's rampant in the school right now, but the school nurse said no one had any severe symptoms, just cough.


Honestly, if the school hadn't asked that we test, I would not have bothered, symptoms were so mild (cough only).

 

[AlanSubie4Life]

Youngest went back to school today, finally had a negative antigen test. No one else has gotten sick in the family, and we didn't take any precautions.

It's rampant in the school right now, but the school nurse said no one had any severe symptoms, just cough.


Honestly, if the school hadn't asked that we test, I would not have bothered, symptoms were so mild (cough only).

Great news. Worst I have heard from people lately is awful sore throat (strep type sore, feels ulcerated but is not) which seems to maybe affect half of people. And maybe some loss of smell briefly. Hopefully nothing long term.

All vaccinated of course. Vaccines work! But could do with some up-to-date mucosal immunity.

 

[JRP3]

Not directly Covid related but it will give the anti vax 5G chip nutters additional fodder for their conspiracies. Pfizer CEO talking about tracking chips in pills for real

 

[NikolaACDC]

Article
https://www.washingtonpost.com/health/2022/05/25/long-covid-vaccines-slight-protection/

about a study by the Department of Veterans Affairs
Long COVID after breakthrough SARS-CoV-2 infection - Nature Medicine

and a report by the CDC
Post–COVID-19 Conditions Among Adult...

"Six months after their initial diagnosis of covid, people in the [VA] study who were vaccinated had only a slightly reduced risk of getting long covid — 15 percent overall. The greatest benefit appeared to be in reducing blood clotting and lung complications. But there was no difference between the vaccinated and unvaccinated when it came to longer-term risks of neurological issues, gastrointestinal symptoms, kidney failure and other conditions.
...
This week, the Centers for Disease Control and Prevention released new estimates of the syndrome’s toll in the United States, suggesting it affects one in five adults younger than 65 who had covid, and one in four of those aged 65 and older. People in both age groups had twice the risk of uninfected people of developing respiratory symptoms and lung problems, including pulmonary embolism, the CDC found. Those in the older age group were at greater risk of developing kidney failure, Type 2 diabetes, neurological conditions and mental health issues.
...
The Veterans Affairs study, believed to be the largest peer-reviewed analysis in the United States on long covid based on medical records, looked at patients who either had two doses of the Moderna or Pfizer—BioNTech vaccines, or one dose of the Johnson & Johnson vaccine. It did not assess the impact of booster shots. While the study population contained a wide range of ages and racial and ethnic backgrounds, it did skew older, Whiter and more male than the United States as a whole.
The VA study also had no way to tell how different variants may change the risk of long covid. These breakthrough infections, for example, took place at a time when alpha, delta and prior variants were at high levels in the United States. It does not cover the period when the omicron variant and its subvariants began circulating in late 2021.
...
The question of vaccines and long covid has been a critical one for doctors. Some patients have claimed a vaccine has cured them, while others have avoided the shots for fear of triggering symptoms.
Igor Koralnik, chief of neuro-infectious diseases at Northwestern Medicine, said recent research suggests neither is true.
...
“There is a neutral effect of vaccination. It didn’t cure long covid. It didn’t make long covid worse,” Koralnik said.
...
David Putrino, a long-covid researcher who serves as director of rehabilitation innovation at the Mount Sinai Health System in New York, shares those concerns. He worries that public health leaders are not taking the current surge seriously enough because they are discounting the risks of long covid.
Putrino said that demand for appointments at his medical center’s long covid clinic continues to increase and he does not anticipate a slowdown any time soon. The clinic has seen about 2,500 patients since opening in May, 2020.
“We failed in our health messaging that death is not the only serious outcome of a covid-19 infection,” Putrino said. “. . . I’m very concerned that what this is going to do is lead us into a continuation of this mass-disabling event we are seeing with long covid.”
____________________

Still better to not get infected...

 

[AlanSubie4Life]

Still better to not get infected...

Yes. Frustratingly little good data on occurrence of long COVID in the vaccinated (and boosted!). Even 1 in ~20 (perhaps) infections yielding long COVID in the CDC data is high but predates Omicron and does not account for vaccination or boosting. It’s a difficult problem to assess but seems risk is probably high enough to try to avoid it, and keep training the body to recognize the pathogen.

Anecdotally I don’t know anyone (yet) infected after vaccination and boosting who has any long COVID symptoms.

 

[AlanSubie4Life]

A point of view on the VA study referenced above.

https://twitter.com/x/status/1529611542043496448

 

[scottf200]

https://twitter.com/x/status/1529628202817228800

 

[JRP3]

Worldometers shows about half as many new cases for yesterday, May 25th, I wonder why the discrepancy?
Interesting to see the areas that are decreasing vs increasing, I wonder which might be a leading indicator?

 

[FlatSix911]

I recommend if you really want to dig deep into how the immune system works in this regard, go read the latest edition of Kuby et al. "Immunology". Great college textbook that is kept up to date by the authors.

EDIT - to be specific - the booster is performing affinity maturation against the ORIGNAL strain. It's unfortunately not able to select out antibodies against the Omicron variant because those Omicron-specific sequences are not present (just sequences common to Omicron and the original strain).

Thanks for the recommendation on the Immunology textbook... I just finished reading the NYT bestseller, Immune and was looking for more information.

Immune: a Journey into the Mysterious System that Keeps…

A gorgeously illustrated deep dive into the immune syst…

www.goodreads.com

 

[bkp_duke]

Thanks for the recommendation on the Immunology textbook... I just finished reading the NYT bestseller, Immune and was looking for more information.

Amazon.com

Not cheap, but it's updated about every 5 years (and this is a slow progressing field).

Amazon.com

www.amazon.com

No affiliation, just considered one of the best nuts+bolts immunology books out there. Fair warning - it's information dense.

 

[AlanSubie4Life]

Worldometers shows about half as many new cases for yesterday, May 25th, I wonder why the discrepancy?
Interesting to see the areas that are decreasing vs increasing, I wonder which might be a leading indicator?

Yeah it is possible we are within a week of a nationwide local peak. The Northeast and Midwest have peaked for now. However, lots of people in CA, FL, and TX. But, those states don’t seem to be accelerating rapidly, and may even be slowing their rate of growth . Reporting will be messed up for the next week or so. South particularly has some room to run, but not clear it will be enough to offset other declines. Maybe Memorial Day will help get things back on track. Sharing is caring.

 

[AlanSubie4Life]

https://twitter.com/x/status/1530275529353355265

Note this is for breakthroughs; assumes vaccination. Those with just one round of infection and no vaccination are going to be in some trouble (with regards to infection at least).

1) BA.4/BA.5 have substantial escape from vaccines and BA.1 breakthrough. BA.2 breakthrough provides substantially better protection against BA.4/BA.5. Indicates that we may see another wave due to BA.4/BA.5 in a couple months, but at least we're getting some good BA.2.12.1 coverage right now (unclear how that will cover BA.4/BA.5 but hopefully at least as good as BA.2).

2) Overall BA.2 is more immunogenic than BA.1. Still less immunogenic than the original.

3) Looks like BA.4/BA.5 and maybe BA.2.12.1 are perhaps a bit more pathogenic. The march to endemicity continues, lol. (As usual, note that Omicron BA.1 was about the same pathogenicity as the Wuhan strain.)

Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis...

www.biorxiv.org

 

[heltok]

Anecdotally I don’t know anyone (yet) infected after vaccination and boosting who has any long COVID symptoms.

My mother had 3x pfizer when she got omicron. Was out for a week, still not fully recovered 4months after. Her husband who introduced it was sick for like a day. Her 4th dose with moderna literally knocked her out, fell, hit her head and struggled with getting up. Imo that 4th dose 2 months after omicron was not positive risk/reward. Does that make me an antivaxxer?

 

[AlanSubie4Life]

Imo that 4th dose 2 months after omicron was not positive risk/reward. Does that make me an antivaxxer?

That sucks. Certainly seems unnecessary to get that dose, but I guess if you had a rough time of the infection maybe it makes sense? Would be better if it were targeted.

The people I know who got Omicron after their boost are not rushing for a fourth. They’ll wait for the retarget assuming they make a good choice with it. BA.2 or something later would be better than targeting BA.1 it seems. They seem to be twiddling their thumbs though.

Maybe after they get results from this trial they won’t bother with trials anymore; that would speed things up.

I certainly don’t have that much faith in my fourth dose of Moderna (changed it up) at this point, other than helping make it a bit more mild, and making it slightly possible I might be immune. I’ll line up for that fifth assuming no infections though. And no major variant change. Ran out of room on my card.

 

[JRP3]

Ran out of room on my card.

Should be room on the back for two more. They gave me a new card after my second booster because they were a bit sloppy when filling out the original shots and over ran the lines. Probably never expected to need more boosters.