We got an early holiday present. One of the last puzzle pieces about the fall booster was released today: data on the effectiveness against severe disease. I also interviewed the CDC Program Lead for more context. Science until now We have ~9 lab studies and 1 real world study showing the fall boosters provide:
I am one of the 12 million? immune compromised and suppressed individuals within the United States that are not only the most vulnerable but the group that has largely been forgotten by the medical community, the general population at largely that refuses to vaccinate and practice mitigation measures, and the government in the race to normalize life. We are the most concerned about what is going on but lately ignored when it comes to information dissemination as it relates to how Covid impact us. Please consider writing a blog that solely relates to us. We are special, we are different and we are being ignored.
Both my wife and I have received the full course of five COVID vaccinations, the most recent one (bivalent) in October. We are planning out-of-the-country travel this spring -- is there any current thinking regarding the utility of getting more (and regular) boosters, even of the same formulation?
Great news. However looking between the lines at the study results, it also appears that the benefit of having 2+ prior MRNA without the new booster is minimal compared to not being vaccinated at all. (e.g. IVY network study showed new booster compared to non-vax was 84% and compared to 2+ MRNA was 73%).
I recognize that the math may not be so simple, but if true, then the stronger message to get the new booster would be that if you're 65+, you're basically unprotected against hospitalization by your prior vaccinations unless you get the booster. Is that a correct conclusion?
We are around three months since the bivalent boosters were released to the general public. Should anyone be thinking about getting a second bivalent shot? Absent further innovation for a new vaccine, what should the timing be for people (both seniors/immunocompromised and healthy adults) to get their next bivalent shot?
Thank you for this analysis. Though you have accurately summarized the take home points from the pair of CDC MMWRs, there are several points that deserve our attention:
First, we must acknowledge that this “proof” that we have been waiting for should have been available prior to the authorization of the bivalent or “fall” booster. Let us not forget that authorization for these products were based on immunogenicity in a handful of rodents only.
It is also important to realize that the FDA is not requiring that the vaccine manufacturers conduct human trials that measure vaccine efficacy with respect to protection from disease or symptoms, the only outcome the public should be interested in.
Every study of these boosters (which are still being conducted) are with regard to immunogenicity only, an outcome that the FDA has long held is not a surrogate for vaccine effectiveness. This is how they justified that everyone should be vaccinated, even people who had prior Covid-19 with documented antibody levels.
Using antibody titers as “proof of effectiveness” of the booster is hypocritical (I will address the uncertainty around the purported effectiveness from the CDC’s most recent studies below).
Second, the CDC has chosen not to conduct a true observational study with matched cohorts and instead is relying on a test-negative, case control methodology. Although this study design has been an accepted method of “estimating” vaccine efficacy since 2005, it is an approach that has its own limitations while providing some reasonable guesses in a cheaper, less time consuming approach.
Simply put, the public deserves better. If the FDA is excusing the vaccine manufacturers from proving that their product actually prevents disease or severe symptoms, the CDC should, at the very least, conduct a prospective observational study that is large enough to prove efficacy and safety.
Thirdly, the CDC’s two MMWRs that are given as reassurance to the public that we have a product that actually works offers us only a modest degree of proof of effectiveness. Here are some important takeaways:
The larger relative Vaccine Efficacy with greater elapsed time since last dose is not an indication that those people who wait to get boosted are better protected. The bigger VE is the result of a monovalent vaccine(s) that has nearly completely waned after a few months.
The 18 and older CDC study w/regard to ED visits:
Using an endpoint of ED or Urgent Care visits is a nebulous outcome as different people have different propensity to seek medical care. Nevertheless, with regard to this outcome, the estimated VE of the booster compared to fully vaccinated is essentially less than 50%, for all groups. The stipulation for emergency use authorization is that the product must demonstrate at least a 50% efficacy. The booster failed to meet minimum requirements for authorization.
To be perfectly accurate, the VE of the booster barely exceeded 50% only in the subgroup of those who received their last monovalent dose 8-10 months prior (53%). So, in order to be in accordance with EUA stipulations, one must wait 8 months before getting boosted.
This poses a practical question: how different will this rapidly mutating virus be in 8 months and what guarantee is there that this formulation will work? We can guess that it will be different and it probably won’t work very well, if at all.
When given to a fully vaccinated person, the booster has a VE of 56% compared to the unvaccinated. This is not statistically different from the VE it offers to a fully vaccinated person. In other words, people who have received the primary series and their last monovalent booster greater than 5 months ago are about at the same risk of getting symptomatic Covid that would land them in the ED as an unvaccinated person.
18 and over w/regard to hospitalization:
With regard to a more definitive outcome, hospitalization, the booster’s effectiveness is under 50% (38-45%) no matter how much time has elapsed since the last monovalent dose.
Puzzlingly, these VEs are calculated using outcomes of people who have gotten the booster within 2-4 months as referent. Where is the calculation with respect to the vaccinated but not boosted? That would be required in order to justify EUA.
The 65 and older study:
The bivalent booster demonstrates a much better estimated effectiveness against hospitalization in the elderly. That’s good.
However, note that the VE of every subgroup (with respect to elapsed time since last monovalent dose) is essentially the same as the absolute VE, or performance compared to the unvaccinated, using 95% confidence intervals.
This means that people in this age group who have gotten 2, 3, or 4 monovalent doses are no better protected than the unvaccinated. Of course, this is a very good reason to get the booster if you are in this age group and vaccinated, but what would be the reason for an unvaccinated person over the age of 65 to begin the primary series at this point?
These findings suggest that at this moment, getting vaccinated is only a temporary measure that will lead to an endless series of boosters as we chase rapidly emerging variants.
Is this really a viable strategy? At what point will we acknowledge that even if there is a miniscule risk of the vaccine, this risk will be additive using this approach?
I get a daily Covid rates update from The NY Times, (which is probably not terribly accurate for all the reasons you’ve outlined in the past). I’ve been watching for the expected surge related to holidays, Thanksgiving especially, but it doesn’t look like there’s been one. Can you address this perception? Inaccurate expectations? Inaccurate data? Something entirely different?
I know a lot of people waiting to get boosted bc they had infections in the last 4-6 months. I, personally, got boosted 3 months after infection and feel like it was probably too early. Unfortunately the message of “get boosted, but not too soon after infection” is a difficult one to get across. I felt very anxious to get it done and now I feel like I’ve set myself up to be much less protected this spring as my natural + vaccine immunity wear off. Any thoughts on that?
Q. For individuals who have had a COVID-19 infection, what is the current recommendation for wait time before getting the bivalent booster shot? I've seen anything from 3 to 6 months after a positive COVID-19 test.
I am a case study in the effectiveness of the new bivalent booster. I tested positive for Covid the Monday before Thanksgiving in the hospital before emergency eye surgery for a detached retina. I couldn't believe it. I had absolutely no symptoms at all. I am 69 years old, fully vaccinated and boosted, and had the bivalent booster about a month before my positive test. The vaccines work! Get them!
After all the requirements that U.S. federal employees get COVID vaccines, here is evidence that at least some federal workers are not being mandated to get the latest bivalent booster shot. From the conversation on this video it's quite clear that this high level officer had the option to get the booster or not get the booster.
But these latest booster shots are being mandated for college students at elite universities. They cannot go to school without the shots. However, everybody else at these universities - the administrators, staff, and professors are not under the same mandate. College students are younger, and thus far less likely to suffer from COVID effects than the typically older staff and professors.
The bivalent booster shots mandate is being justified by Yale University with this statement:
"We are requiring students to receive the bivalent booster because their circumstances are somewhat different from those of faculty and staff, especially with regard to congregate housing and participation in large gatherings." The spokesperson noted that students can "seek an exemption from the booster requirement on medical or religious grounds."
The problem with this is that the CDC has web pages saying COVID shots are perfectly safe for everybody, with no exceptions. So why are medical exemptions being allowed? Has the federal government produced any documents on who should be allowed to get a medical exemption from any type of COVID shot? Anybody heard of any guidance anywhere on who could or should get a medical exemption? Seems like medical exemptions are kind of arbitrary and entirely dependent on opinions - which are likely to be quite different from place to place.
Unfortunately my questions are unlikely to be answered by the CDC or U.S. Public Health Service which is not mandating the bivalent booster for it's employees .
I am one of the 12 million? immune compromised and suppressed individuals within the United States that are not only the most vulnerable but the group that has largely been forgotten by the medical community, the general population at largely that refuses to vaccinate and practice mitigation measures, and the government in the race to normalize life. We are the most concerned about what is going on but lately ignored when it comes to information dissemination as it relates to how Covid impact us. Please consider writing a blog that solely relates to us. We are special, we are different and we are being ignored.
I so appreciate your summaries. Only wish our governor, Ron DiSantis, would read you, too .
Both my wife and I have received the full course of five COVID vaccinations, the most recent one (bivalent) in October. We are planning out-of-the-country travel this spring -- is there any current thinking regarding the utility of getting more (and regular) boosters, even of the same formulation?
Great news. However looking between the lines at the study results, it also appears that the benefit of having 2+ prior MRNA without the new booster is minimal compared to not being vaccinated at all. (e.g. IVY network study showed new booster compared to non-vax was 84% and compared to 2+ MRNA was 73%).
I recognize that the math may not be so simple, but if true, then the stronger message to get the new booster would be that if you're 65+, you're basically unprotected against hospitalization by your prior vaccinations unless you get the booster. Is that a correct conclusion?
We are around three months since the bivalent boosters were released to the general public. Should anyone be thinking about getting a second bivalent shot? Absent further innovation for a new vaccine, what should the timing be for people (both seniors/immunocompromised and healthy adults) to get their next bivalent shot?
Thank you for this analysis. Though you have accurately summarized the take home points from the pair of CDC MMWRs, there are several points that deserve our attention:
First, we must acknowledge that this “proof” that we have been waiting for should have been available prior to the authorization of the bivalent or “fall” booster. Let us not forget that authorization for these products were based on immunogenicity in a handful of rodents only.
It is also important to realize that the FDA is not requiring that the vaccine manufacturers conduct human trials that measure vaccine efficacy with respect to protection from disease or symptoms, the only outcome the public should be interested in.
Every study of these boosters (which are still being conducted) are with regard to immunogenicity only, an outcome that the FDA has long held is not a surrogate for vaccine effectiveness. This is how they justified that everyone should be vaccinated, even people who had prior Covid-19 with documented antibody levels.
Using antibody titers as “proof of effectiveness” of the booster is hypocritical (I will address the uncertainty around the purported effectiveness from the CDC’s most recent studies below).
Second, the CDC has chosen not to conduct a true observational study with matched cohorts and instead is relying on a test-negative, case control methodology. Although this study design has been an accepted method of “estimating” vaccine efficacy since 2005, it is an approach that has its own limitations while providing some reasonable guesses in a cheaper, less time consuming approach.
Simply put, the public deserves better. If the FDA is excusing the vaccine manufacturers from proving that their product actually prevents disease or severe symptoms, the CDC should, at the very least, conduct a prospective observational study that is large enough to prove efficacy and safety.
Thirdly, the CDC’s two MMWRs that are given as reassurance to the public that we have a product that actually works offers us only a modest degree of proof of effectiveness. Here are some important takeaways:
The larger relative Vaccine Efficacy with greater elapsed time since last dose is not an indication that those people who wait to get boosted are better protected. The bigger VE is the result of a monovalent vaccine(s) that has nearly completely waned after a few months.
The 18 and older CDC study w/regard to ED visits:
Using an endpoint of ED or Urgent Care visits is a nebulous outcome as different people have different propensity to seek medical care. Nevertheless, with regard to this outcome, the estimated VE of the booster compared to fully vaccinated is essentially less than 50%, for all groups. The stipulation for emergency use authorization is that the product must demonstrate at least a 50% efficacy. The booster failed to meet minimum requirements for authorization.
To be perfectly accurate, the VE of the booster barely exceeded 50% only in the subgroup of those who received their last monovalent dose 8-10 months prior (53%). So, in order to be in accordance with EUA stipulations, one must wait 8 months before getting boosted.
This poses a practical question: how different will this rapidly mutating virus be in 8 months and what guarantee is there that this formulation will work? We can guess that it will be different and it probably won’t work very well, if at all.
When given to a fully vaccinated person, the booster has a VE of 56% compared to the unvaccinated. This is not statistically different from the VE it offers to a fully vaccinated person. In other words, people who have received the primary series and their last monovalent booster greater than 5 months ago are about at the same risk of getting symptomatic Covid that would land them in the ED as an unvaccinated person.
18 and over w/regard to hospitalization:
With regard to a more definitive outcome, hospitalization, the booster’s effectiveness is under 50% (38-45%) no matter how much time has elapsed since the last monovalent dose.
Puzzlingly, these VEs are calculated using outcomes of people who have gotten the booster within 2-4 months as referent. Where is the calculation with respect to the vaccinated but not boosted? That would be required in order to justify EUA.
The 65 and older study:
The bivalent booster demonstrates a much better estimated effectiveness against hospitalization in the elderly. That’s good.
However, note that the VE of every subgroup (with respect to elapsed time since last monovalent dose) is essentially the same as the absolute VE, or performance compared to the unvaccinated, using 95% confidence intervals.
This means that people in this age group who have gotten 2, 3, or 4 monovalent doses are no better protected than the unvaccinated. Of course, this is a very good reason to get the booster if you are in this age group and vaccinated, but what would be the reason for an unvaccinated person over the age of 65 to begin the primary series at this point?
These findings suggest that at this moment, getting vaccinated is only a temporary measure that will lead to an endless series of boosters as we chase rapidly emerging variants.
Is this really a viable strategy? At what point will we acknowledge that even if there is a miniscule risk of the vaccine, this risk will be additive using this approach?
I get a daily Covid rates update from The NY Times, (which is probably not terribly accurate for all the reasons you’ve outlined in the past). I’ve been watching for the expected surge related to holidays, Thanksgiving especially, but it doesn’t look like there’s been one. Can you address this perception? Inaccurate expectations? Inaccurate data? Something entirely different?
I know a lot of people waiting to get boosted bc they had infections in the last 4-6 months. I, personally, got boosted 3 months after infection and feel like it was probably too early. Unfortunately the message of “get boosted, but not too soon after infection” is a difficult one to get across. I felt very anxious to get it done and now I feel like I’ve set myself up to be much less protected this spring as my natural + vaccine immunity wear off. Any thoughts on that?
Is there any hope for a pan-valent vaccine in the near future?
Great interview with Dr. Link-Gellles. Also your participation in PBS Newshour yesterday. Keep up the good work!
Thank you! Great summary!
Q. For individuals who have had a COVID-19 infection, what is the current recommendation for wait time before getting the bivalent booster shot? I've seen anything from 3 to 6 months after a positive COVID-19 test.
"Compared to no prior vaccination, effectiveness of the fall booster against hospitalization was 84%.
Compared to 2+ previous mRNA vaccines, effectiveness was 73%."
How were those percentages calculated using hospital data? Can I get some details on that? Thanks.
I am a case study in the effectiveness of the new bivalent booster. I tested positive for Covid the Monday before Thanksgiving in the hospital before emergency eye surgery for a detached retina. I couldn't believe it. I had absolutely no symptoms at all. I am 69 years old, fully vaccinated and boosted, and had the bivalent booster about a month before my positive test. The vaccines work! Get them!
Thank you so much. I look forward to all of your posts. I love learning and being informed.
Thanks, great news!
After all the requirements that U.S. federal employees get COVID vaccines, here is evidence that at least some federal workers are not being mandated to get the latest bivalent booster shot. From the conversation on this video it's quite clear that this high level officer had the option to get the booster or not get the booster.
But these latest booster shots are being mandated for college students at elite universities. They cannot go to school without the shots. However, everybody else at these universities - the administrators, staff, and professors are not under the same mandate. College students are younger, and thus far less likely to suffer from COVID effects than the typically older staff and professors.
The bivalent booster shots mandate is being justified by Yale University with this statement:
"We are requiring students to receive the bivalent booster because their circumstances are somewhat different from those of faculty and staff, especially with regard to congregate housing and participation in large gatherings." The spokesperson noted that students can "seek an exemption from the booster requirement on medical or religious grounds."
The problem with this is that the CDC has web pages saying COVID shots are perfectly safe for everybody, with no exceptions. So why are medical exemptions being allowed? Has the federal government produced any documents on who should be allowed to get a medical exemption from any type of COVID shot? Anybody heard of any guidance anywhere on who could or should get a medical exemption? Seems like medical exemptions are kind of arbitrary and entirely dependent on opinions - which are likely to be quite different from place to place.
Unfortunately my questions are unlikely to be answered by the CDC or U.S. Public Health Service which is not mandating the bivalent booster for it's employees .