COVID What are the Correlations Between Vaccine Side Effects & Antibody Levels?

[berkeman]

TL;DR Summary

Have there been any studies trying to correlate the vaccine efficacy level with the severity of the side effects experienced with each vaccination?

(Sorry if this has already been addressed in one of the other COVID-19 threads. If it has, I can delete my question or merge it into the other thread. Thanks.)

I work part-time in EMS, so I was in tier 1A for public vaccinations for COVID-19 here in Northern California. I got my first Moderna shot a few days ago, and aside from some deltoid pain, I have not experienced any other side effects. I'm active on a Medic forum (EMTLife.com), and there is a long thread there for Medics to share their experiences with each of the doses of the vaccines (many of the full-time Medics are now past their 2nd dose). The side effects vary all over the map, seemingly independent of the person's background, medical history, and level of fitness.

So since I have experienced no side effects at all, I started wondering if that might be an indicator of how my body was responding to the first vaccination shot. Does it mean that my body is ignoring it, and I'll be in the 40% of folks who get no benifit from the first vaccine? Or is it a good indicator that my body handles infection challenges well (which is my history), and is building up the antibodies without bothering to tell me about it?

It would seem that the vaccine trials would have tracked side effects from each of the immunization shots, as well as antibody levels and whether the subjects were in the 90% that were eventually protected, or in the unlucky 10% who still lost the infection battle and developed full-blown COVID-19. Are any such study correlations published? I would be very interested to see what they have found. Thanks.

 

[FactChecker]

There may not be enough data to answer this for the COVID-19 vaccinations, but it is known for the flu shots. After a flu vaccination, the absence of side effects does not indicate that the shot did not "take".

 

[jim mcnamara]

There is no correlation. Vincent Raconiello - virologist - Runs a weekly podcast, part of the time they answer letters. This was asked.

They referred viewers to CDC's Fauci and his comment on the the subject - The reaction intensity does not relate to any disease level you would have had without the vaccination. And any level of subsequent protection. So a weak reaction is not something to worry about.

This Week In Virology - TWIV. TWiV #715 1:05:10 from the start.
https://www.microbe.tv/twiv/ There are literally 700+ of these panel discussions, this one is for the first week of Feb 2021, recorded 02/02/2021

 

[berkeman]

Great, good to know. Thanks folks!

 

[russ_watters]

They referred viewers to CDC's Fauci and his comment on the the subject - The reaction intensity does not relate to any disease level you would have had without the vaccination.

How is that measured/known? How do you measure the intensity of something that doesn't happen? Do they do that by comparing with other diseases/vaccines? E.G., someone who has an intense reaction to the flu vaccine doesn't necessarily get intensely sick from the flu? Then they figure it works the same for COVID?

I tend to have a significant reaction to flu vaccines (one of the reasons I rarely get them), but don't often get the flu or get it badly if I do. I guess you are saying these (thin, anecdotal) observations are unconnected?

 

[berkeman]

I tend to have a significant reaction to flu vaccines (one of the reasons I rarely get them), but don't often get the flu or get it badly if I do.

What kind of reaction do you typically have to the flu vaccine?

 

[russ_watters]

What kind of reaction do you typically have to the flu vaccine?

The normal one: flu symptoms. Wasn't that the thrust of your question?

 

[berkeman]

Yes, but fever, chills, muscle aches, GI tract issues, or the whole shebang? If a fever, do you know about what it peaks out at and how long it lasts?

 

[russ_watters]

Yes, but fever, chills, muscle aches, GI tract issues, or the whole shebang? If a fever, do you know about what it peaks out at and how long it lasts?

Usually not GI tract issues (I didn't even realize that was a common flu symptom) but everything else. I've never measured my perceived post-vaccine fever, so I can't give any data. Symptoms generally last about 1-2 days.

Jim's answer surprised me, which is why I'm asking about the other side of the coin/how it is known.

 

[berkeman]

Usually not GI tract issues (I didn't even realize that was a common flu symptom)

Apparently it's more common in kids compared to adults:

https://www.cdc.gov/flu/symptoms/fl...eling feverish,common in children than adults

The main difference in COVID-19 symptoms compared to the flu is more Shortness of Breath and the loss of taste and/or smell.

 

[FactChecker]

Apparently it's more common in kids compared to adults:

https://www.cdc.gov/flu/symptoms/flu-vs-covid19.htm#:~:text=• Fever or feeling feverish,common in children than adults

View attachment 277540

The main difference in COVID-19 symptoms compared to the flu is more Shortness of Breath and the loss of taste and/or smell.

The flu can also cause shortness of breath because of pneumonia. That is how the flu typically kills. The flu and pneumonia are combined in one number in the government death statistics.

 

[berkeman]

The flu can also cause shortness of breath because of pneumonia.

True, but I think SOB (dyspnea) is generally a late sign for the flu. It is an early sign for COVID-19, and along with loss of smell/taste is a differentiator between COVID-19 and the flu:

https://www.uspharmacist.com/article/coronavirus-flu-shortness-of-breath-provides-a-clue

Coronavirus? Flu? Shortness of Breath Provides a Clue

By staff

Lessons from a group of healthcare providers at Cambridge Health Alliance who set up an ambulatory clinic shortly before the pandemic surge reached their community could help pharmacists and others identify patients likely infected with SARS-CoV-2 in the absence of definitive testing. In turn, that could help them guide patients to the OTC products best suited to their ailments and educate patients about when to see a physician.

In an article in the April 13 issue of Mayo Clinic Proceedings, they noted that patients infected with the novel Coronavirus presented with a wide range of respiratory and gastrointestinal (GI) symptoms, as well as headache, back pain, myalgia, and fatigue commonly associated with influenza, bronchitis, or GI viruses.

They found that one early indicator of a SARS-CoV-2 infection was loss of smell, which commonly occurred in the first few days of illness.

While many patients with mild cases recover within 2 or 3 weeks, a significant number deteriorate and start to experience labored breathing. “The onset of dyspnea is the point at which COVID-19 can begin to be discerned from other common illnesses,” they said.

Generally, the downward trend is noticeable 4 to 8 days after symptoms start, but they found that a few patients developed dyspnea somewhat later. The timing of dyspnea distinguishes COVID-19 from other infections with similar presentation.

 

[berkeman]

How is that measured/known? How do you measure the intensity of something that doesn't happen? Do they do that by comparing with other diseases/vaccines? E.G., someone who has an intense reaction to the flu vaccine doesn't necessarily get intensely sick from the flu? Then they figure it works the same for COVID?

I tend to have a significant reaction to flu vaccines (one of the reasons I rarely get them), but don't often get the flu or get it badly if I do. I guess you are saying these (thin, anecdotal) observations are unconnected?

Jim's answer surprised me, which is why I'm asking about the other side of the coin/how it is known.

@jim mcnamara may not have seen this, so I'll flag him to get his thoughts.

 

[jim mcnamara]

@FactChecker ICD-10 provides international guidelines for recording mortality. The CDC complies with them. AFAIK. That does not mean that press releases created by HHS politcal appointees do or do not comply.
Where did you see it? (FLU+PNEU = flu deaths)

From the ICD-10 document at the CDC site:

The International Classification of Diseases (ICD) is designed to promote international comparability in the collection, processing, classification, and presentation of mortality statistics. This includes providing a format for reporting causes of death on the death certificate. The reported conditions are then translated into medical codes through use of the classification structure and the selection and modification rules contained in the applicable revision of the ICD, published by the World Health Organization (WHO). These coding rules improve the usefulness of mortality statistics by giving preference to certain categories, by consolidating conditions, and by systematically selecting a single cause of death from a reported sequence of conditions. The single selected cause for tabulation is called the underlying cause of death, and the other reported causes are the nonunderlying causes of death. The combination of underlying and nonunderlying causes is the multiple causes of death.

This is a political football IMO. I can find where there are accusations about this on either side:
"you should lump flu death with pneumonia death"
versus
"you should not lump flu death with pneumonia deaths"

This is one complaint about a report conflating, done by CDC:
https://aspe.hhs.gov/cdc-—-influenza-deaths-request-correction-rfc

 

[jim mcnamara]

@russ_watters @berkeman
It sounds like you may not have hit the TWIV site - understandable

They mention Fauci and then point out that there is no vaccine followup data that supports a correlation.
They also point out that extreme reaction to the Moderna vaccine is less than 1 in 100,000, based on FDA mandated vaccine RCT's and followup data from vaccine sites.

So, if you want people to get vaccine what would you say that would not be anti-vaxxer fodder?

Also consider fatality rates: for New Mexico is 1.91% of people diagnosed with a test, die - i.e., seropositive people do sometimes die. Contrari-wise the same RCT shows that after 28 days those vaccinated showed no fatalities whereas the control group did have fatalities.

The point is: the fatality ratio exceeds known severe vaccine reaction by 3 orders of magnitude. You decide correlations. I say no correlation known.

 

[russ_watters]

@russ_watters @berkeman
It sounds like you may not have hit the TWIV site - understandable

They mention Fauci and then point out that there is no vaccine followup data that supports a correlation.
They also point out that extreme reaction to the Moderna vaccine is less than 1 in 100,000, based on FDA mandated vaccine RCT's and followup data from vaccine sites.

So, if you want people to get vaccine what would you say that would not be anti-vaxxer fodder?

Also consider fatality rates: for New Mexico is 1.91% of people diagnosed with a test, die - i.e., seropositive people do sometimes die. Contrari-wise the same RCT shows that after 28 days those vaccinated showed no fatalities whereas the control group did have fatalities.

The point is: the fatality ratio exceeds known severe vaccine reaction by 3 orders of magnitude. You decide correlations. I say no correlation known.

This answer doesn't sound at all related to my question.

But no, videos/podcasts are tough to wade through to find specific info in, so I didn't dive in.

 

[hutchphd]

Summary:: Have there been any studies trying to correlate the vaccine efficacy level with the severity of the side effects experienced with each vaccination?

Does it mean that my body is ignoring it, and I'll be in the 40% of folks who get no benifit from the first vaccine?

Please be aware that there is no such 40% who get no benefit. The data plainly shows that a single shot provides >90% protection from day twelve onward. Assuming a 5 day incubation period that means that 7 days after shot one you are protected to 90%.
The Israelis understand this as do the Brits. I have been trying to promote "jab everybody once" with some success, and it is imperative not to misstate the data. The 60% number includes the people in the first week who were got sick (dumb) and only goes out to week 3 (dumb). See insert graph. Please we need to jab everybody once quickly.
edit:This is Pfizer submission

Please do not promulgate that 60% nonsense...

 

[FactChecker]

@FactChecker ICD-10 provides international guidelines for recording mortality. The CDC complies with them. AFAIK. That does not mean that press releases created by HHS politcal appointees do or do not comply.
Where did you see it? (FLU+PNEU = flu deaths)

From the ICD-10 document at the CDC site:This is a political football IMO. I can find where there are accusations about this on either side:
"you should lump flu death with pneumonia death"
versus
"you should not lump flu death with pneumonia deaths"

This is one complaint about a report conflating, done by CDC:
https://aspe.hhs.gov/cdc-—-influenza-deaths-request-correction-rfc

What the CDC wants and what it gets may be two different things.
From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2636436/ :
" Epidemiologists, demographers, and vital statisticians analyze mortality from influenza and pneumonia combined as a single cause. This is because influenza kills through pneumonia and is coded as such on death certificates. "

 

[bhobba]

Interesting question. In the UK the only vaccines they have data on are the Pfizer and Oxford vaccines. Aus where I am will not start vaccination until the end of the month and will use the same vaccines as the UK - it could start now but because it is well under control here will wait to see what happens elsewhere.

First off the rank will be the Pfizer Vaccine, and then the Oxford Vaccine. I am in group 2 - those over 60 with comorbidities - and will not get it until group 1 is done - it probably will be the Pfizer vaccine and some more than just mild reactions have been reported. That I think is why they recommend a 15 minute wait at where you get it before leaving. No 15 minute wait is required for the Oxford vaccine.

At the moment Pfizer is generally considered more effective. But then again effective has a number of different measures eg the percentage of people that get infected when vaccinated (here Pfizer wins), how well it protects others from catching it or does it only suppress symptoms, if you do get it when vaccinated how bad is the disease you get etc. At the moment I don't think we know the answer to the latter questions - although the latest data on the Oxford Vaccine looks promising in that it may reduce transmission by 67%:
https://www.ox.ac.uk/news/2021-02-0...stained-protection-76-during-3-month-interval

So one could say, that with our current preliminary data, the more effective Pfizer vaccine may have a worse reaction profile - but with caveats eg how do we measure efficacy? We need to analyse more data before making the call. Either way though both vaccines produce side effects - but mostly benign:
https://www.bbc.com/news/health-55932832.

Bottom line IMHO more research needs to be done on this and, in practice, as of now, I do not think it really matters which vaccine you get. These are only the initial vaccines. Work is progressing on second generation vaccines:
https://www.scientificamerican.com/article/the-second-generation-covid-vaccines-are-coming/

The fat lady has not sung yet by a long shot. And good it has not:


Possible 7 years till we get back to normal - I wince just thinking about it. I will do a separate post about that.

Thanks
Bill

 

[bhobba]

Please we need to jab everybody once quickly.

Yes - there is value in that - although that is not how the stage 3 trials were done so in a sense we are taking a 'punt' - but IMHO a reasonable one. I will re-post the latest data on the Oxford vaccine that certainly supports that view, but from a different source with more info on dosing levels:
https://theconversation.com/astraze...eases-protection-according-to-new-data-154617

It seems, at least for the Oxford vaccine, 'The exploratory analyses presented in this preprint suggest that it is the dosing interval and not the dosing level which has a great impact on the efficacy of the vaccine.' It may be that the half dose first then the full dose weeks later may be the best approach as was accidentally found in the trials - but more work on that I think is necessary. Exactly what initial protection would a half dose give? All the other vaccine makers should gather similar data - it would be very valuable. Hopefully they are.

Thanks
Bill

 

[jim mcnamara]

Assume you want to reduce Covid fatalities- your foremost goal. What do you do?

Spoiler

Give highest vaccination priority to the population that has the highest fatality rate

 

[bhobba]

Assume you want to reduce Covid fatalities- your foremost goal. What do you do?

Your spoiler is correct. But there are other factors. And that is why I have been prioritised with the the Pfizer vaccine here in Aus - after essential front line workers and the like who are in phase 1a. I said before I was in phase 2 - actually it is phase 1b - don't you love bureaucratic designations.

But there are other factors. If it turns out 'that it is the dosing interval and not the dosing level which has a great impact on the efficacy of the vaccine.' then that dramatically changes the strategy. You certainly still vaccinate the vulnerable and those caring for the vulnerable first, but get that first dose, which could even be a half dose, to everyone as quickly s possible, doing the second dose after perhaps everyone has already had the first shot. I think an all out effort getting that first dose out in 12 weeks is possible logistically - but the current management likely will need to improve. I think here in Aus it could be done to virtually everyone with a concerted effort.

BTW the reason those caring for the vulnerable are given priority even over the actual vulnerable is there have been some horror stories of those carers killing large numbers of vulnerable in nursing homes and the like. Very strict protocols are now in place here in Aus to try and prevent that, and they are getting stricter all the time as weaknesses are discovered (they should have been done initially IMHO - but that is another story).

Thanks
Bill

 

[FactChecker]

Assume you want to reduce Covid fatalities- your foremost goal. What do you do?

Spoiler

Give highest vaccination priority to the population that has the highest fatality rate

That seems very likely, but it would be worth some analysis. To your knowledge, has there been an analysis of that question? It might be better to target those who get around and spread the disease. Or the vaccine might be more effective on younger people (like with the flu shot, where the elderly need a triple-strength vaccine) and they should be targeted. It is a complicated thing.

 

[jim mcnamara]

Let's try this.
Here is some CDC data and some assumptions about who/when to vaccinate

Assumptions:

Covid fatalities normally use hospital ICU facilities for longer periods than do survivors
Give 20 million vaccinations and reduce fatalities and hospital use most effectively
Give healthcare personnel vaccinations = ~ 1 million doses
Comorbidities effects are included in the CDC table, advanced age greatly increases likelihood of comorbidities

Example Solution:
Prioritize vaccination for elderly population to reduce impact on healthcare facilities
Example: 1B classification for vaccine eligibility in New Mexico is age 75, or one of several comorbidities

As of 2/7/2021 10:08:45
using: https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm#AgeAndSex
which was current to 2/3/2021

Covid deaths, sample exclusion by age class from early vaccination, percent mortality excluded out of 421379
Start with excluding age 44 and younger.
Example estimate using the CDC table:
If you vaccinate persons > age 74 you reduce fatalities by 421378 - ( .284*421378)
which is ~301706 fewer deaths from Covid.

patients < age45 
(44 + 23 + 67 + 601 + 2677 + 7057) / 421378
  =.0248, 2.4%  percent of fatalities excluded
 
patients < age55
(44 + 23 + 67 + 601 + 2677 + 7057 + 19454) / 421378
  =.0710, 7.1% percent of fatalities excluded

patients < age65
(44 + 23 + 67 + 601 + 2677 + 7057 + 19454 + 49141) / 421378
  =.1876, 18.8% percent of fatalities excluded

patients < age75
(44 + 23 + 67 + 601 + 2677 + 7057 + 19454 + 49141 + 89896) / 421378
  =.2843, 28.4% percent of fatalities excluded

This is why I think a way to reduce Covid impact with limited supplies of vaccine is to
vaccinate people more likely to make extended use of ICU's.

Perfect solution is to vaccinate everyone. Good luck with that.

 

[berkeman]

Please do not promulgate that 60% nonsense...

Interesting. I will have to find where I heard/read the 60-70% number for the 1st shot, and 90% for the 2nd. After all, they are using 2 shots for a reason to get to 90%. I think it might have been Fauci, but it could have been an epidemiologist MD in a radio interview. Will try to find it...

 

[Ygggdrasil]

That seems very likely, but it would be worth some analysis. To your knowledge, has there been an analysis of that question? It might be better to target those who get around and spread the disease. Or the vaccine might be more effective on younger people (like with the flu shot, where the elderly need a triple-strength vaccine) and they should be targeted. It is a complicated thing.

Researchers have used mathematical models to study which groups should get priority in order to reduce deaths, the groups most at risk of mortality or the groups at most risk of spreading the disease. While they find that vaccinating younger people first does minimize transmission, it does a worse job at minimizing mortality than vaccinating older people first:

“Almost no matter what, you get the same answer,” says Harvard epidemiologist https://www.hsph.harvard.edu/marc-lipsitch/. Vaccinate the elderly first to prevent deaths, he says, and then move on to other, healthier groups or the general population. One recent study modeled how Covid-19 is likely to spread in six countries—the U.S., India, Spain, Zimbabwe, Brazil, and Belgium—and concluded that if the primary goal is to reduce mortality rates, adults over 60 should be prioritized for direct vaccination. The study, by Daniel Larremore and Kate Bubar of the University of Colorado Boulder, Lipsitch, and their colleagues, has been published as a preprint, meaning it has not yet been peer reviewed.

https://www.scientificamerican.com/...math-on-who-should-get-a-covid-vaccine-first/

Here's a link to the pre-print manuscript cited:
Model-informed COVID-19 vaccine prioritization strategies by age and serostatus
https://www.medrxiv.org/content/10.1101/2020.09.08.20190629v3

Abstract:

Limited initial supply of SARS-CoV-2 vaccine raises the question of how to prioritize available doses. Here, we used a mathematical model to compare five age-stratified prioritization strategies. A highly effective transmission-blocking vaccine prioritized to adults ages 20-49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults over 60 years old. Use of individual-level serological tests to redirect doses to seronegative individuals improved the marginal impact of each dose while potentially reducing existing inequities in COVID-19 impact. While maximum impact prioritization strategies were broadly consistent across countries, transmission rates, vaccination rollout speeds, and estimates of naturally acquired immunity, this framework can be used to compare impacts of prioritization strategies across contexts.

 

[FactChecker]

Researchers have used mathematical models to study which groups should get priority in order to reduce deaths, the groups most at risk of mortality or the groups at most risk of spreading the disease. While they find that vaccinating younger people first does minimize transmission, it does a worse job at minimizing mortality than vaccinating older people first:https://www.scientificamerican.com/...math-on-who-should-get-a-covid-vaccine-first/

Here's a link to the pre-print manuscript cited:
Model-informed COVID-19 vaccine prioritization strategies by age and serostatus
https://www.medrxiv.org/content/10.1101/2020.09.08.20190629v3

Abstract:

So once again, the experts are way ahead of the amateur (myself). I should have guessed that. That makes me happy. :-)

 

[Ygggdrasil]

Please be aware that there is no such 40% who get no benefit. The data plainly shows that a single shot provides >90% protection from day twelve onward. Assuming a 5 day incubation period that means that 7 days after shot one you are protected to 90%.
The Israelis understand this as do the Brits. I have been trying to promote "jab everybody once" with some success, and it is imperative not to misstate the data. The 60% number includes the people in the first week who were got sick (dumb) and only goes out to week 3 (dumb). See insert graph. Please we need to jab everybody once quickly.

I agree that the first dose of the vaccine offers effective (~90%) protection, however, it is likely that a prime dose of the vaccine will not induce effective long term immunity without a booster dose. The prime-boost strategy that most vaccines employ was not decided upon for some arbitrary reason. There is a lot of research supporting the idea that booster shots are needed to induce long term immunological memory to the pathogen being vaccinated against. Most vaccines are delivered with a priming dose + one or more booster doses for this reason. Unfortunately, the one vaccine most people receive frequently (the flu vaccine) is given only as one shot because it is intended only to provide short term (~ 6 months) protection (longer term protection is less useful against the influenza virus given the rapid changes in flu strains year-to-year).

It is likely that SARS-CoV-2 is going to stay around, and become an endemic virus that circulates in human populations like the other four endemic cold-causing coronaviruses. These cold-causing coronaviruses likely do not cause severe disease in people because people become exposed at an early age (where, as in the case of COVID-19, infection is not likely to cause severe disease) and develop immunity to protect against severe disease in the future. Especially for the vulnerable populations being vaccinated now (at least in the US, most locales have moved to phase 1b where people >65 are being vaccinated), I think it is crucial to provide the two doses that are necessary to induce long term immunity.

As we move toward vaccinating the general population (who have less risk of severe disease), I could see the argument for providing short-term immunity through only one dose of the vaccine. However, Manaus, Brazil provides a cautionary tale of the potential that herd immunity could be short lived. Manaus experienced a severe outbreak of the disease in Spring 2020, such that some studies estimated that ~75% of the population became infected (though some researchers suggest that this number is overestimated). Despite the large fraction of infected individuals, however, the city experienced a second wave of the virus recently, seeing hospitalization rates higher than those seen during the first wave in Spring 2020.

There are a number of (non-mutually exclusive) different potential explanations that could contribute to the resurgence of COVID in Manaus: 1) The prevalence of COVID-19 could have been overestimated, 2) immunity to the virus may wane over a short period of time, 3) The P.1 strain evades immunity (likely via the E494K mutation), and 4) The P.1 strain has a higher transmissibility (likely due to the N501Y mutation). The Lancet article I cited above discusses these possibilities further:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00183-5/fulltext

As for the possibility of immunity waning over time, we know from studies on people who were infected by the similar SARS virus from the 2003 outbreak also suggests that levels of antibodies against the virus wane over the course of a few years (though the caveat is that we don't know how much antibody is necessary for immunity). This matches our experience with the four other endemic coronaviruses suggests that infection provides short term immunity that wanes over time (potentially as short as ~6 months). Of course, we don't know whether the current vaccines will produce long-term immunity that will last longer than a few months, but two doses give the best shot at inducing longer-term immunity.

 

[hutchphd]

but two doses give the best shot at inducing longer-term immunity.

That may all be exactly as you say although much of it is "best guess". It is still an insane policy to withhold initial immunizations from at risk individuals based on some arbitrary 3 wk interval. Three thousand people a week are perishing in the US. I suggest that it is prudent to plan for everyone getting a booster and produce vaccine according. We should begin them just as soon as everyone who wants an initial dose is accommodated.

It is also also possible that the later booster could mitigate against the very latest mutated strain of the virus should this be necessary. I'm sorry but the current policy seems absurdly conservative and not well considered to provide maximum expected benefit.

I personally will forego my second injection (first jab next week) until everyone in U.S. is accommodated. I request everyone do similarly.

 

[Ygggdrasil]

That may all be exactly as you say although much of it is "best guess". It is still an insane policy to withhold initial immunizations from at risk individuals based on some arbitrary 3 wk interval.

It is considerably more than an arbitrary interval and best guess. These practices are based off of considerable experience gathered from work with other vaccines and reflect the best available science. Of course, biology is quite complicated, and we can't really know for sure in the absence of clinical trials that test and measure the duration of immunity.

 

[hutchphd]

These practices are based off of considerable experience gathered from work with other vaccines and reflect the best available science.

I am really interested in a few concrete examples of this science. My complaint with medical practice is that "prevailing wisdom" just sort of grows without attribution, becomes part of the canon, and then is declared science. So far I am unaware of the data and would really like to see some. I'll bet it is pretty thin.
But if I hear one more "expert" pompously declare the initial single Pfizer shot only 60% effective I will need medication or at the least clean underwear..
And I fully agree with the desire for definitive data. But unfortunately this will not be quick. Absent a raging pandemic the delay is warranted: not so much right now. One jab, thank you very much.

 

[berkeman]

But if I hear one more "expert" pompously declare the initial single Pfizer shot only 60% effective I will need medication or at the least clean underwear..

LOL.

One jab, thank you very much.

Well, I'll be admistering those jabs in a few weeks at our local mass vaccination sites, so I'll be getting my 2nd vaccine on time.

 

[hutchphd]

Well I do think you should. But I don't require it as a citizen.
Do you understand my argument about the 60% number? That really is a miscarriage of analysis of the Pfizer data. I have spent twenty-five years dealing with statistical "experts" who really don't understand statistics, so it wasn't a stretch for me. The Pfizer data is essentially mute on the second shot question. Too bad there was not a cohort with no second shot but I think no one suspected the data would be otherwise so definitive. In retrospect ~3000 people with only one shot would have been sufficient, but we can't go back.
Good luck.

 

[FactChecker]

How is that measured/known? How do you measure the intensity of something that doesn't happen?

I don't know how they test it, but they can determine if your blood contains antibodies.

Do they do that by comparing with other diseases/vaccines? E.G., someone who has an intense reaction to the flu vaccine doesn't necessarily get intensely sick from the flu? Then they figure it works the same for COVID?

I tend to have a significant reaction to flu vaccines (one of the reasons I rarely get them), but don't often get the flu or get it badly if I do. I guess you are saying these (thin, anecdotal) observations are unconnected?

Although it is not true that the absence of a noticeable response means that the vaccination did not take, it seems logical that the presence of a noticeable response means that the vaccination did take. It probably also means that your immune system was already ready to defend against the virus. They say that the reaction to the second COVID shot tends to be more severe than to the first shot because the immune system is already better prepared to act. That may be why you do not get severe flu -- your immune system is ready for it ( indicated by the fact that it over-reacts to the flu shot).
In any case, that seems logical to an amateur like me.

 

[bhobba]

It is likely that SARS-CoV-2 is going to stay around, and become an endemic virus that circulates in human populations like the other four endemic cold-causing coronaviruses. These cold-causing coronaviruses likely do not cause severe disease in people because people become exposed at an early age (where, as in the case of COVID-19, infection is not likely to cause severe disease) and develop immunity to protect against severe disease in the future. Especially for the vulnerable populations being vaccinated now (at least in the US, most locales have moved to phase 1b where people >65 are being vaccinated), I think it is crucial to provide the two doses that are necessary to induce long term immunity.

You bet. See the RSV virus:
https://www.mayoclinic.org/diseases...-syncytial-virus/symptoms-causes/syc-20353098

The parallels to Covid is uncanny. So contagious everyone gets it by 2 years of age, and like Covid in such young people usually causes little or no issues - but for a small number can. You develop immunity and in older children and adults is responsible for 20% of colds. The issue comes as you get older your immune system becomes less effective and if you get it then - watch out:
https://www.cdc.gov/rsv/factsheet-older-adults.pdf

Sound familiar? I suspect, even with continuing development of vaccines, and possible treatments, Covid will go down a similar path.

Regarding the two dose issue, as I mentioned in previous posts, for the Oxford vaccine most will get in Aus, it is now thought one dose gives 76% protection for 12 weeks, and then with a second dose about 83%. If the second dose is given less then 6 weeks later it was only about 55% effective. Strange.

The only 10% effectiveness against the South African variant that stopped South Africa's vaccine programme I think is an overreaction. In one year I recall the flu vaccine only had a 10% effectiveness, but it was still used. It is all set to go so why not proceed? They have a variant of the vaccine in the works to target the SA variant that is hoped to be available well before years end, and that could be deployed later. I think like the flu virus it is here to stay and we may need a shot or two every year.

Thanks
Bill

 

[bhobba]

It is considerably more than an arbitrary interval and best guess. These practices are based off of considerable experience gathered from work with other vaccines and reflect the best available science. Of course, biology is quite complicated, and we can't really know for sure in the absence of clinical trials that test and measure the duration of immunity.

I know you are talking about the Pfizer and Moderna vaccines predominant in the US, but the latest data suggests for the Oxford vaccine (which will be the main vaccine in many countries like Australia) the main determinant of effectiveness seems to be how much later you get the second shot. 12 weeks seems about optimum. They only found this out via a mistake - half dose first then 90 days later the second dose produced 90% protection. The main factor for the better immunity seems to be the delayed second dose. I think the effect of a half or full first dose is minimal, at least according to an article I previously posted 'Although not directly presented in the paper, it appears that with a 12-week gap between doses there was very little difference in efficacy for those receiving an initial half or full dose.'. If true we could quickly inoculate with kalf doses, then as supplies of the vaccine build up give the second full dose. Australia has been producing doses since late November so already has a reasonable stockpile.

Added later. Just a note that this was found out by pure luck. The UK went against the science and decided to vaccinate as many as possible with a first shot, delaying the second shot. Many people, including me, were appalled at this. But, lucky for Boris, this turned out to be, at least for the Oxford vaccine, the best strategy. Boris was lucky, very lucky. It's good for Aus though allowing more to be vaccinated with the first dose, leaving the second dose for 3 months when our stockpile will be even greater. If I was Boris I would not push my luck too far. This worked well, and something valuable was discovered, but the odds are it will blow up in your face next time.

Thanks
Bill

 

[Tom.G]

Just a note (coincidence?) about the Moderna vaccine.

Today three of us received the first dose of the Moderna COVID vaccine. A few hours later we all took naps, ranging from 1/2 to 2.5 hours. Two of us were one hour short of sleep to begin with.

 

[bhobba]

Just a note (coincidence?) about the Moderna vaccine. Today three of us received the first dose of the Moderna COVID vaccine. A few hours later we all took naps, ranging from 1/2 to 2.5 hours. Two of us were one hour short of sleep to begin with.

I think that fits in with the UK experience where, as I previously posted, 1/3 had a reaction, the vast majority, minor, and tiredness was one of them. I am on insulin now for my Diabetes and even that makes me a bit tired. So off for a bit of a snooze before ordering dinner. The local restaurant has these BBQ beef ribs I have become addicted to.

Thanks
Bill

 

[atyy]

It is considerably more than an arbitrary interval and best guess. These practices are based off of considerable experience gathered from work with other vaccines and reflect the best available science. Of course, biology is quite complicated, and we can't really know for sure in the absence of clinical trials that test and measure the duration of immunity.

I am really interested in a few concrete examples of this science. My complaint with medical practice is that "prevailing wisdom" just sort of grows without attribution, becomes part of the canon, and then is declared science. So far I am unaware of the data and would really like to see some. I'll bet it is pretty thin.
But if I hear one more "expert" pompously declare the initial single Pfizer shot only 60% effective I will need medication or at the least clean underwear..
And I fully agree with the desire for definitive data. But unfortunately this will not be quick. Absent a raging pandemic the delay is warranted: not so much right now. One jab, thank you very much.

Of course a trial for a delayed booster would be best. But I think the idea to vaccinate more people with the first dose, and delay the second (given supply limitations) has some backing with other vaccines. For example, for some vaccines the booster has a minimum interval, rather than a maximum interval.
https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/timing.html
https://www.immunize.org/technically-speaking/20120301.asp
"First, let’s clear up one popular misconception; there is no such thing as a "maximum interval." With very limited exceptions (e.g., oral typhoid vaccine in certain circumstances), you do NOT need to restart a vaccine series because an interval is longer than recommended. Doses given even years later than recommended are still valid because the body has “immunologic memory.” The real problem with longer than recommended intervals is not the validity of the doses or their immunologic effect. It is that, until the series is complete, the person may remain susceptible to the associated vaccine-preventable disease."

 

[bhobba]

Of course a trial for a delayed booster would be best.

I think, at least for the Oxford Vaccine, that has been done. Boris, in the UK, took a punt to give the first dose to all he can and 12 weeks for the second dose. It turned out to be the right choice, but based on the data when he made the decision it was 'risky'. The first dose still provided about 76% effectiveness which is still good. As a quote I gave previously suggested even a half dose gave good initial protection, but did not give the exact amount. I would have hesitated doing it without further data - but then again there was the big 'hint' of 90% effectiveness with a half dose and a full dose 90 days later. Considering how bad the situation is in the UK it would be very tempting to do it. These are the hard choices leaders have to make. As for Pfizer and Moderna I think it best to go with what was used in the stage 3 trials, but prioritise testing for the optimum time between doses, and optimum first dose. I suspect it is already underway, as is testing a first dose of one vaccine then a second dose of a different one.

Added Later:
It seems for the Pfizer vaccine the first dose confers 90% protection:
https://www.sciencefocus.com/news/pfizer-vaccine-single-dose-90-per-cent-effective-after-21-days/

So even for that vaccine the second dose later strategy could have value.

Thanks
Bill

 

[Ygggdrasil]

I think, at least for the Oxford Vaccine, that has been done. Boris, in the UK, took a punt to give the first dose to all he can and 12 weeks for the second dose. It turned out to be the right choice, but based on the data when he made the decision it was 'risky'. The first dose still provided about 76% effectiveness which is still good. As a quote I gave previously suggested even a half dose gave good initial protection, but did not give the exact amount. I would have hesitated doing it without further data - but then again there was the big 'hint' of 90% effectiveness with a half dose and a full dose 90 days later. Considering how bad the situation is in the UK it would be very tempting to do it. These are the hard choices leaders have to make. As for Pfiser and Moderna I think it best to go with what was used in the stage 3 trials, but prioritise testing for the optimum time between doses, and optimum first dose. I suspect it is already underway, as is testing a first dose of one vaccine then a second dose of a different one.

Here's the data from the non-peer reviewed pre-print on the Oxford-AstraZeneca vaccine:

Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268

While the data suggest a higher vaccine efficiency with >12 week delay between the first and second doses, it's worth noting that the number of individuals studies is still fairly low (thousands of participants vs tens of thousands in the phase 3 clinical trials used to provide data supporting EUA of the Pfizer-BioNTech and Moderna vaccines). The confidence intervals of the data are still quite wide and overlap between the <6 weeks and >12 weeks groups, so while the data are suggestive, collection of more data would be warranted.

The 76% effectiveness of one dose quoted in the data reflects only the period 22-90 days after vaccination. The data also seems to suggest that the protection from the single dose could wane after 90 days:

Again, the numbers for the longer time periods are quite small, so more data collection is needed to draw stronger conclusions.

A lot of these conclusions about the timing of the two doses could be specific to adenoviral vector vaccines like the Oxford-AstraZeneca and Johnson & Johnson vaccines (the Pfizer-BioNTech and Moderna vaccines are based on a different technology, mRNA vaccine technology). Because the adenoviral vector vaccines use adenoviruses to deliver the spike protein DNA into cells, there are concerns that the first dose could generate immunity to the adenoviral vector that could interfere with delivery of the second dose (and these concerns would not apply to the mRNA vaccines). See this post for more discussion: https://www.physicsforums.com/threads/coronovirus-vaccine-progress.992484/page-4#post-6454249

 

[neilparker62]

LOL.

Well, I'll be admistering those jabs in a few weeks at our local mass vaccination sites, so I'll be getting my 2nd vaccine on time.

All the best - I'm trying to think of a good slogan but the best I can come up with is: "Jabbers of the World unite!" (my sister-in-law has also joined the ranks in the UK).

 

[bhobba]

This whole thing is crazy. On one of our expert panel shows, the best known one in fact, called Q&A, last Thursday they had a discussion with immunologists etc on the vaccine. At the moment here in Aus we are churning out over 50 million doses of the Oxford Vaccine. After that we will churn out over 50 million doses of the Novavax vaccine - or buy it in - our manufacturer CSL has not decided yet - it is likely however we will make it to prevent supply problems like with the Pfizer Vaccine. We have 20 million doses (enough for 10 million people - 1/5 of our population) of the Pfizer vaccine to be rolled out at the end of the month, the Oxford in March sometime. One of these 'experts', Dr Michelle Ananda-Rajah, made the claim forget about the Oxford vaccine, and go straight to the Novavax vaccine because the Oxford vaccine only has 63% efficiency while the Novavax vaccine has 95% efficiency (from early phase 3 results). None of other 'experts' challenged her on that. I was sitting there thinking what's going on here - haven't they seen the latest data on the Oxford vaccine?

https://www.astrazeneca.com/media-c...the-primary-analysis-of-phase-iii-trials.html

One dose - 76% effective. After 12 weeks you get the second dose - 82% effective.

She has interesting views:
https://twitter.com/rajah_mich?ref_src=twsrc^google|twcamp^serp|twgr^author

Below she acknowledges the new data about efficacy, but still took it at 63% because she has some doubts about it (which seems to be the reason she didn't mention it):
https://healthcareworkersaustralia.com/2021/02/11/backing-up-our-gains/

To me the road ahead here in Aus is obvious - high priority groups get the Pfizer, we give one dose of the Oxford as fast as possible to the rest of Aus. Then the second dose 12 weeks later. It will probably take longer than 12 weeks to give the first dose to everyone - it is estimated October, so 3 months after that for everyone to get the second dose. Once the Novavax vaccine is manufactured it can then be rolled out - exactly when depending on how it interacts when already vaccinated with the Oxford or Pfizer and how long the immunity lasts - but I suspect next year sometime. Australia, being in a very good position, deliberately has decided to wait a while and get the data from other counties vaccine use before proceeding. And I think it was wise - we now know the most effective dosing for the Oxford vaccine. I am in the priority one group of 16 million so I may or may not get the Pfizer - personally though I would prefer the Oxford because I take strong precautions - leave the moderately more effective vaccine for those that may not be as carefull as I am.

But as the good doctor/immunologist correctly points out it will not get us out of trouble - many restrictions will still remain here in Aus. It will be less when the Novavax vaccine is rolled out, but I personally doubt even that will do it. I fear we are in for, an admittedly lessening, level of restrictions for a few years yet, until things get back to normal.

Added later
Actually had a reply from the good doctor to my twitter post. Her blog I posted made some valid points:

'Announcement on Feb 1 of increased efficacy by spacing two doses of the AZ vaccine at least 12 weeks apart generated some interest. This post hoc analysis of the primary clinical trial data should be interpreted with caution. Post hoc analyses aim to ask a question rather than answer one. Why? Because they rely on analysing a slice of the main trial data; have greater uncertainty around estimates because numbers analysed are usually smaller and are prone to bias which may translate to inadvertently finding patterns where there are none. This sub-study provided the rationale for the UK vaccine authority’s decision to delay the interval between vaccine doses to at least 12 weeks in order to vaccinate more people. However, a quarter of a year is a long time to wait in the middle of a pandemic. This sub-study actually raised more questions than answers (as post hoc analyses often do!). Why was the efficacy of a single dose of the AZ vaccine at preventing symptomatic infection higher than two standard doses at 76% versus 63% respectively? In other words, vaccine efficacy seemed to decline with a second dose. This trial update contained an additional 5,541 people from SA, UK and Brazil but overall vaccine efficacy with two standard doses remained unchanged from the first interim study published on Dec 8 which led to approvals in several countries (i.e. 63% among 14,379 people in this update vs 62% in the first analysis). Reassuringly, there were no hospitalisations after the second vaccine dose (n=0 with vaccination vs 15 with control). These results will reassure Britons that delaying the second dose by 12 weeks has some supportive evidence. However, for the rest of us, we keenly await the release of the AZ trial predominantly from the US with >32K people where close to one quarter will be over 65 years, due to report in the next month or so. In this large trial, people are receiving 2 standard doses 28 days apart- potentially the dosing schedule we will receive if approved, hence discussions on single dosing and delayed interval dosing of 12 weeks are largely academic for Australia.'

The statistician in me (sigh) unfortuneately agrees. There goes another 'good' idea. We can alter the timeframe of our second dose, but for some reason she seems to think the dosing schedule here is going to be 28 days. We have, lies, damned lies, and statistics or as my stats prof used to say - stats is like a bikini, it's the bits you don't see you want to know about. However trials, as detailed in my first link, are proceeding with different dosings and times between the second shot.

Thanks
Bill

 

[Jansky]

I don't know how they test it, but they can determine if your blood contains antibodies.

This is the classical method and not necessarily the way that currently antibodies and their specificity are generally tested but the basic theory applies to all antibody tests including the test strip ones. The convenient advantage/disadvantages are that it is very low-tech and quite sensitive but somewhat slow, requiring hours to overnight to analyze.

The Ouchterlony double immunodiffusion test
https://en.wikipedia.org/wiki/Ouchterlony_double_immunodiffusion

In addition and what this thread doesn't seem to recognize is that along with antibodies the second arm of the immune system the cellular immune reaction mediated by T-cells, NK(natural killer)cells, macrophages, dendritic cells and others, can have an even more long term protective and clearing effectiveness of viruses even with lowered Ab levels. And that this cellular activation is what is responsible during immunization to mediate the so called side effects of the earlier responses to the vaccination reactions through substances such as prostaglandins, leukotrienes and protein mediators such as cytokines and is quite unrelated to the slower generation of the antibodies response requiring days to weeks to fully mature.

 

[Mary Conrads Sanburn]

Last updated February 17, 2021 at 5:10 PM

[. . .]

“The CA Department of Public Health ended the Regional Stay Home Order across California. This action came as projected ICU availability rose above 15%. Counties have returned to their assigned Blueprint tiers and are urged to continue safe practices, avoiding crowds and wearing a mask when leaving home.”

[. . .]

https://covid19.ca.gov/safer-economy/

I live in California! I take Gracie Girl dog and me to parks that have now opened! Of course I love the hills in Benicia and Pt Pinole

 

[Mary Conrads Sanburn]

Covid-19 testing is required prior to my Cataract Surgery. Not looking forward for that!
All I can do is have happy thoughts. Life is a journey ~~~. I think I'm going to write some
poetry. It always relaxes me. Thank you bhobba for the tumbs up! It helped.

 

[Mary Conrads Sanburn]

I walked from home to the hospital today. I went to the lab and a nice person swabbed my nose

to test for Covid prior to my surgery.

 

[Mary Conrads Sanburn]

I had Post-Op Eye Drop Instructions after Cataract Surgery:

Ofloxacin – This is an antibiotic in order to prevent infections. One drop to the operated eye.

3 times per day (morning, noon, night) x 1 week. This drop is to be obtained from my local pharmacy with prescription.

Ketorolac – This is an anti-inflammatory medication to help the eye heal. One drop to the operated eye

3 time per day (morning, noon, night) continue drops until further instructed. This drop is to be obtained from my local pharmacy with prescription.

Week 2: KETOROLAC

2x/day (morning, night)

Week 3:

2x/day (morning, night)

Week 4:

2x/day (morning, night)

# # #

There was no pain! I am so happy to have my “healthy” left eye thanks to the surgeon and his medical staff! Of course, I thank them and those who gave me a thumbs up bhobba .

 

[bhobba]

No problrmo. Interestingly your regime after cataract surgery was exactly the same as my mother had for hers. Took a bit of time off work to help her because she had bad arthritis in the hands. I was thinking of driving her to the doctor to get it done, but he walked me through it all over the phone - it was easy-peasy.

Thanks
Bill

 

[Mary Conrads Sanburn]

Dear Bill,
You are a great son with a heart of gold!