Coronavirus

[Jeff N]

The very solid evidence (very large dataset, and peer-reviewed methods to deal with observational bias) we have is 88% (symptomatic) efficacy against Delta from PHE (no vaccine-type breakout of their recent 79% number). However, that was with a longer dosing interval.

Didn’t the UK start with Pfizer later on? I think I recall that their data doesn’t extend as long as Israel’s. I think the Pfizer CEO claimed the UK and Israel data was consistent if you matched time periods. It isn’t clear to me that the conjecture about the importance of the time gap between first and second doses (3 vs 12 weeks) has been conclusively demonstrated. It wouldn’t surprise me if it were partially true but what is the actual effect?

As I said, I wouldn’t be shocked at a drop of efficacy from 80% to 60% in older people who are 8 months out, but as an average efficacy, I would be pretty surprised actually, based on the evidence so far.

I think the Pfizer CEO said they weren’t seeing large differences in efficacy fade based on age although he thought that might make sense for people who are otherwise immunologically compromised. We haven’t seen all of that data published yet, I think.

And I have no concerns that the booster will restore efficacy to good levels close to (but lower than) the trials. It has to be lower than the trials, not because it is delta immune escape, but because people are being exposed to higher viral loads. That lowers actual efficacy (vaccinated people are more likely to become infected, while the risk to unvaccinated people is much less dependent on the viral dose, since they have no barrier to infection). The higher viral loads are both because of delta, maybe, and because of reduced mask use, etc, quite likely.

The Pfizer CEO said the 3rd shot raised antibody levels 10x times the level reached soon after the 2nd shot and 100x times higher than the levels reached ~8 months after the 2nd shot. Those levels may well offset the increase in viral load. I don’t think you can say that 1000x nasal viral load means 1000x transmissibility. We’ve only seen overall transmissibility estimated as being 2-3x higher. Things are complicated.

 

[AlanSubie4Life]

Or even an updated version more effective against the latest variant.

Yes, though those are likely to be so far off that there probably won't be the opportunity to wait that long, since waning likely will occur in enough of the population after 9-12 months that any booster is probably better.

They're only just starting trials now so I wouldn't anticipate actual updates to the vaccine until next year.

Studies to Address Emerging Variants | Pfizer

www.pfizer.com

And if Moderna's results are anything to go by, the targeting of Delta may not help all that much - they're just planning for a reduced dose of the original since it seems to make minimal difference vs. one targeted at Beta (also, the immune system naturally evolves to deal with variants, as it turns out - sounds crazy but apparently this is a thing...):

https://investors.modernatx.com/static-files/c43de312-8273-4394-9a58-a7fc7d5ed098 (starting slide 24)

 

[AlanSubie4Life]

It wouldn’t surprise me if it were partially true but what is the actual effect?

No one knows. It's just a known difference that may have an effect. It may also have minimal to no effect.

Pfizer CEO said the 3rd shot raised antibody levels 10x times the level reached soon after the 2nd shot and 100x times higher than the levels reached ~8 months after the 2nd shot.

It would be good to see detailed data from them both on their antibody levels and their clinical trial results (which are ongoing, as linked above).

A 10x antibody level increase from the original level (that increase can be defined in many ways and I wonder how it is defined here - GMT?) may provide minimal additional protection - it's not clear. At some point, you probably do reach a limit where for reasons unrelated to antibody levels, the infection can break through in some individuals, probably setting the ceiling for efficacy. 100x the 8 month level, yes, that probably does provide protection against delta and other earlier variants as well. As you say, things are complicated (and very non-linear).

We'll see what the trials say. I do think it's very likely it improves efficacy! Just not clear whether it is needed for most people at this time, and it's certainly not the optimal strategy to stop any winter wave. All depends on whether we're interested in saving lives and ending the pandemic and keeping hospitals properly loaded, or whether we want to really protect the people who are already vaccinated (and remain well protected against hospitalization) who want to be vaccinated again. (I say we just do both, but focus on getting vaccination rates up, no matter what people say about not wanting them. Keep pushing and addressing their concerns.)

Pfizer CEO said they weren’t seeing large differences in efficacy fade based on age

I'm not sure how they would know. Older people got vaccinated earlier and were of a different economic status most likely. I mean, it is knowable, eventually. Would just be good to see the data.

I'm very interested in particular in the severe data. Once that starts ticking up substantially there's a MUCH stronger argument for boosters.

Hopefully Pfizer is not using these data! (I'm sure they are not) ->

https://twitter.com/x/status/1427650571515928591

 

[Jeff N]

I'm not sure how they would know. Older people got vaccinated earlier and were of a different economic status most likely. I mean, it is knowable, eventually.

They may have data from health care workers (certainly in the Israeli data) who received the vaccine around the same time as the first group of older folks. Also, there is on-going study of the people in the phase 3 trials that covers a wide age range.

 

[eevee-fan]

Refuse vaccine and you get a monthly check. LOL

 

[AlanSubie4Life]

They may have data from health care workers (certainly in the Israeli data) who received the vaccine around the same time as the first group of older folks

Right but that would be hard because that is not a representative group. I guess I’m general you’d expect such a group to wane less - but also their exposures are completely different than the normal population!

Also, there is on-going study of the people in the phase 3 trials that covers a wide age range.

Yes that will be interesting to see and as a randomized blinded study should provide some clarity, though I wonder if it will be sufficiently powered (maybe less than prior trials). Probably will be the best we get though. I doubt it will have sufficient power to show clear trends in efficacy vs. age but I hope I am wrong. Hopefully in the end overall efficacy against any symptomatic disease gets boosted way up. And hopefully protection against severe disease remains very strong or even improves.

 

[Slipstream]

Regarding the booster: we know mixing mRNA with AstraZeneca or Jaansen is being recommended.

What about if you started with an mRNA (Pfizer or Moderna)? Would you do a different mRNA for the booster (i.e. if you had Pfizer first, do Moderna for the booster, or vice-versa) or stick with the same mRNA type?

I know some will say it doesn’t matter, but perhaps there’s data out there to show it does matter. I’ve searched and can’t find anything so far.

 

[AlanSubie4Life]

Well, the Biden administration is saying boosters after 8 months (seems long).

Claims are:
- Waning antibodies
- Delta may require higher levels of neutralizing antibodies to protect against infection
- Variety of data indicate waning efficacy against delta over time (particularly in older groups but unclear how that was separated from waning).

I guess one of these days we’ll get solid data on what is happening so people can understand their risks, but it appears to no longer matter!

 

[madodel]

Well, the Biden administration is saying boosters after 8 months (seems long).

Claims are:
- Waning antibodies
- Delta may require higher levels of neutralizing antibodies to protect against infection
- Variety of data indicate waning efficacy against delta over time (particularly in older groups but unclear how that was separated from waning).

I guess one of these days we’ll get solid data on what is happening so people can understand their risks, but it appears to no longer matter!

Initially I think they want to concentrate the boosters on the most at risk (elderly and immunocompromised) and health care workers who started getting vaxxed in January. My wife will be very happy. She had Pfizer in January. The rest of us have to wait and the people in poor countries will just have to wait longer.

 

[Jeff N]

I think the Pfizer CEO said they weren’t seeing large differences in efficacy fade based on age although he thought that might make sense for people who are otherwise immunologically compromised.

This general claim about age was re-enforced in this morning’s White House Covid briefing where they announced the new booster shot plan. Surgeon General Murthy briefly addresses this around the 32 minute mark.

 

[AlanSubie4Life]

This general claim about age was re-enforced in this morning’s White House Covid briefing where they announced the new booster shot plan. Surgeon General Murthy briefly addresses this around the 32 minute mark.

Yeah. I think in general this is the right decision (precautionary principle), and I don’t see why it necessarily has to limit doses to the rest of the world significantly (it’s not clear to me that supply is the only limitation in rollout).
But data on who is vulnerable and how vulnerable they are remain sparse. In some ways it reminds me of last year’s recommendations on masks, and various other recommendations which weren’t strongly supported by evidence (some of which turned out to be the right call).

Still, I believe the most effective way for vaccinated people to avoid infection is to have others get vaccinated. I think this is pretty clear but I guess it is not an obtainable goal? I didn't hear that emphasized this morning, though they did talk about the importance of getting vaccinated, they did not mention to vaccinated people that the path to minimum risk is for others to get vaccinated. Anyway, we should not lose sight of that if we want to avoid a winter wave and reduce infection risk. Seems like now everyone is just going to be worrying about their boosters, which for most people probably don’t matter much (data lacking!).

 

[Jeff N]

Initially I think they want to concentrate the boosters on the most at risk (elderly and immunocompromised) and health care workers who started getting vaxxed in January. My wife will be very happy. She had Pfizer in January. The rest of us have to wait and the people in poor countries will just have to wait longer.

The recommendation is to get the booster 8 months after the previous shot. The vaccinations early in the year started slowly and didn’t really get rolling until February. From March onward, many of those doses were 2nd shots.

As these boosters are rolling out gradually in the U.S., vaccine manufacturing at multiple companies will at the same time be greatly ramping up far in excess of the 3rd shots that will be administered here. So, the overall effect of 3rd doses here will have a relatively small impact on the total vaccine shots available globally.

 

[Jeff N]

But data on who is vulnerable and how vulnerable they are remain sparse.

In particular, the folks briefing us today were pretty vague about the future waning of t-cell response and thus most of the protection against hospitalization and death. The early data around that seems to be confused and inconsistent right now.

 

[JRP3]

 

[Jeff N]

View attachment 698204

Yes! An immediate regimen of Z-Pak Azithromycin is highly contraindicated. Hydroxychloroquine too!

 

[AlanSubie4Life]

In particular, the folks briefing us today were pretty vague about the future waning of t-cell response and thus most of the protection against hospitalization and death. The early data around that seems to be confused and inconsistent right now.

The MMWRs for today are available here at the top of the page (this link will become out of date with time):

Home page for MMWR | MMWR

The Morbidity and Mortality Weekly Report (MMWR) Series is prepared by the Centers for Disease Control and Prevention (CDC).

www.cdc.gov

Sustained Effectiveness of Pfizer-BioNTech and...

COVID-19 vaccine effectiveness against hospitalizations was stable for people who received 2 doses, and vaccines remained effective among people with risk for severe COVID-19.

www.cdc.gov

Effectiveness of Pfizer-BioNTech and Moderna Vaccines in...

COVID-19 mRNA vaccines, Pfizer-BioNTech and Moderna, are effective against infection among nursing home residents, but effectiveness declined in recent months.

www.cdc.gov

In particular, the one for New York is interesting. Obviously has limitations, but it's a study of the entire state population, and the results do seem good.
Notably, note that reduced efficacy over time is being driven (in this study) by the YOUNGER population. To me that implies that the vaccine alone is not enough to prevent infection (regardless of variant, perhaps, though undoubtedly delta plays a part, based on the modest reduction in neutralizing titer due to delta), and layered approaches (more likely to be employed by older people?) are a good idea - and they seem to work against delta.

Also indicates efficacy against hospitalization is strong and sustained (in this study - the other studies don't really look at it.):

New COVID-19 Cases and Hospitalizations Among...

COVID-19 vaccine effectiveness against hospitalizations was stable, but it declined against new infections among adults in New York during May–July 2021.

www.cdc.gov

 

[madodel]

Yes! An immediate regimen of Z-Pak Azithromycin is highly contraindicated. Hydroxychloroquine too!

So you are going with the ivermectin, right?

 

[NikolaACDC]

CDC brings in high-profile outsiders to launch new center aimed at improving disease outbreak forecasting

"The agency has faced some criticism throughout the COVID-19 pandemic for struggling to model coronavirus outbreaks and sharing key data too slowly, making it difficult for decision-makers to react in real time and come up with clear response policies. But on Tuesday, the CDC announced a new offshoot, led by high-profile outside experts who have come to the forefront during the pandemic such as Drs. Marc Lipsitch and Caitlyn Rivers, that's aimed at improving disease outbreak forecasting.

The CDC's Center for Forecasting and Outbreak Analytics will focus on three key functions, the agency said: predicting the course of outbreaks, data sharing and integration, and translating and communicating the forecasts for policy-makers."
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Should be very useful.

 

[Krugerrand]

My partner was reading an article written by a nurse who has had to deal with dying children and parents who insist that the kid must be dying of something else because COVID is fake. If I was in that position, I would tell them, "what we have is a pandemic of stupidity and you have a bad case of it. Your child is dying because of your infection."

I've also heard that nurses are quitting because they can't take the consequences of idiocy they see on a daily basis. It was one thing when we didn't have vaccines and people were getting sick because they made a mistake and got exposed, or were forced into a dangerous work environment because of their economic situation. It's a completely different situation when there is a vaccine that, at minimum can reduce the chances of a severe infection significantly and people are refusing to get it.

My ICU nurse friend is at their breaking point. They tell me that family members of patients in ICU are calling up, yelling at them, claiming their loved one doesn't have COVID, that they're making things up, it's all misdiagnoses, that they're killing their loved ones. It's absolute insanity.

 

[NikolaACDC]

Third Pfizer Vaccine Dose Shown To Be 86% Effective In Preventing Covid Among The Elderly

"Initial study results published Wednesday by Maccabi Health Services found 37 people out of 149,144, or 0.02%, who received three doses of the Pfizer vaccine have tested positive for Covid-19, compared to 1,064 of the 675,630 people, or nearly 0.2%, who only received a second dose in January or February.
Maccabi, one of Israel’s top four healthcare providers, said it ensured the two groups had similar demographics and found the third doses were 86% effective after at least one week.
...
“The triple dose is the solution to curbing the current infection outbreak,” Dr. Anat Ekka Zohar, who led the Maccabi study, said of the recent outbreak in Israel, which last month became one of the first nations to authorize booster shots for people ages 60 and over. "
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Seems another 'Yay' for booster shots.