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ACIP Meeting, CDC
September 19, 2025COVID -19 Vaccine Discussion
Framing, 2025-2026
Professor Retsef Levi, PhD, MIT
ACIP Meeting, CDC
September 19, 2025WG Main Takeaways
•Assessments of the protection level provided by COVID -19 vaccines and especially
seasonal boosters against severe outcomes (hospitalization, ICU, death, long- covid)
are based on very low -quality data and analyses
•Vaccine injuries are demonstrably not recognized by current pharmacovigilance
systems, leaving vaccine injured individuals abandoned and without appropriate care
•Ample published research suggests serious safety uncertainties and concerns, including potential adulteration (mRNA vaccines), that are currently not appropriately addressed
ACIP Meeting, CDC
September 19, 2025WG Recommended Actions
•The risks and uncertainties related to the COVID -19 vaccine should be appropriately
communicated by CDC to patients and medical providers to enable appropriate informed
consent (WG recommendations regarding the Vaccine Information Statement)
•Development and enhancement of national efforts to appropriately diagnose the vaccine injured and care for them (WG will continue discussions in coming months)
•Development and enhancement of national safety surveillance systems to address safety uncertainties and assess impact (WG will continue discussions in the coming months)
ACIP Meeting, CDC
September 19, 2025COVID-19 Vaccine Benefits: Quality of Evidence
The WG could not receive reliable assessments of the Number Needed to Vaccinate
(NNV) related to different sub- groups and outcomes:
Presentation to COVID -19 Work Group September 12, 2025 by the University of Michigan
ACIP Meeting, CDC
September 19, 2025Quality of Evidence re COVID -19 Vaccine Benefits
Estimates from the UK greatly differ from the CDC estimates:
UK Health Security Agency (UKHSA) NVV estimates for the
2024- 2025 season
Appendix A: estimating the number needed to vaccinate to
prevent a COVID -19 hospitalisation in autumn 2024 in
England - GOV.UK
ACIP Meeting, CDC
September 19, 2025Quality of Evidence re COVID -19 Vaccine Benefits
Estimates from the UK greatly differ from the CDC estimates:
UK Health Security Agency (UKHSA) NVV estimates for the 2024 -2025
season
Appendix A: estimating the number needed to vaccinate to prevent a
COVID -19 hospitalisation in autumn 2024 in England - GOV.UK
ACIP Meeting, CDC
September 19, 2025Methodological Limitations
•WG members felt that the current working definition of the CDC regarding COVID -19
associated hospitals does not seem to meaningfully capture the clinical impact of
SARS- CoV-2 infections on severe COVID -19 outcomes
•Only 30% of patients under current definition have COVID as primary discharge diagnosis
Trends in COVID -19–Attributable Hospitalizations Among Adults With Laboratory -Confirmed SARS -CoV -2—COVID -NET, June
2020 to September 2023 - Taylor - 2024 - Influenza and Other Respiratory Viruses - Wiley Online Library
ACIP Meeting, CDC
September 19, 2025Methodological Limitations
•WG members felt that the current methodology to assess vaccine efficacy (VE) is
prone to major biases:
“The design cannot be used for studying the mortality effects of vaccines and is
problematic for studies into the effect on hospitalization. The vaccine's effectiveness on the transmission of viruses is also potentially problematic, depending very much on the characteristics of the tests. The implication of our findings is that the test -negative
designs can, at best, be seen as an indication of effectiveness in highly idealized situations that are often far away from reality.”
https://onlinelibrary.wiley.com/doi/10.1111/jep.13888
ACIP Meeting, CDC
September 19, 2025Test-Negative- Design
N = population size= Nv + Nuv
Unknown number of vaccinated
(Nv) and unvaccinated (Nuv)
Cv = # of vaccinated
covid cases Cuv = # of unvaccinated
covid cases Ov = # of vaccinated
controlsOuv = # of unvaccinated
covid controls
ACIP Meeting, CDC
September 19, 2025NTD - Main Idea
•Ideally the relative risk would be calculated as 1- (Cv/Cuv)÷(Nv/Nuv), but Nv/Nuv not
observed!
•Approximate it with the observed Ov/Ouv assuming the control cases are not affected
by/correlated with vaccination status and therefore are drawn at random from the
population
•Attempt to mitigate biases because health- seeking behavior (people who arrived to
the hospital)
•Under assumptions provide an unbiased estimator of the relative risk reduction
ACIP Meeting, CDC
September 19, 2025Potential Biases of NTD
•The estimate of Ov/Ouv (for unobserved Nv/Nuv) is prone to many biases:
•Hospitalizations of controls (and cases) might be triggered by other (non-
respiratory) medical conditions
•Vaccinated test more when they have a cold
•Vaccine could make vaccinated more vulnerable to other cold infections
•Healthy vaccinee effect (HVE)
https://www.nejm.org/doi/full/10.1056/NEJMc2306683
ACIP Meeting, CDC
September 19, 2025Other VE Assessment Approaches
•Matched cases (exact on based on propensity scores)
•Use of negative controls to capture unobserved biases
•Randomized control clinical trials (RCTs)
Note:
RCTs of mRNA vaccines did not show benefits for all cause mortality & hospitalizations
https://pubmed.ncbi.nlm.nih.gov/37163200/
https://pubmed.ncbi.nlm.nih.gov/36055877/
ACIP Meeting, CDC
September 19, 2025Other Concerns regarding VE
•WG members were concerned that the boosters’ protection seems to be short -term
•WG members were concerned by published and unpublished research that suggest
negative efficacy or increased vulnerability to other respiratory viruses:
https://academic.oup.com/ofid/article/10/6/ofad209/7131292?login=false
https://www.nature.com/articles/s43856- 025-01046-8
https://www.medrxiv.org/content/10.1101/2023.12.07.23298573v3
ACIP Meeting, CDC
September 19, 2025COVID- 19 Burden Decreases
Presentation to COVID -19 Work Group September 12, 2025 by the University of Michigan
ACIP Meeting, CDC
September 19, 2025Safety Concerns and Uncertainties
WG members felt that CDC currently does not appropriately acknowledge several
safety concerns & uncertainties:
•Outcomes and prognosis of myocarditis and other cardiovascular adverse events
•Clinically documented prolonged vaccines injuries, specifically post vaccine syndrome (PVS)
•Multiple documented unintended mechanisms of action of the mRNA vaccines and seemingly regulatory violations
ACIP Meeting, CDC
September 19, 2025Deaths from Myocarditis
Autopsies of 2 teenage boys in the US who died in their sleep 3 & 4 days
post Pfizer Dose 2
ACIP Meeting, CDC
September 19, 2025Deaths from Myocarditis
CDC response
ACIP Meeting, CDC
September 19, 2025Deaths from Myocarditis
Pathologist response
ACIP Meeting, CDC
September 19, 2025Subclinical myocarditis may occur in up to 3% post vaccination
Teenage boys post dose 2
Adult healthcare workers post booster
dose
ACIP Meeting, CDC
September 19, 2025Deaths from Subclinical Myocarditis
Korean study of 44 million vaccinated
•95 cases severe vaccine related myocarditis
•85 ICU admissions
•36 cases of fulminant myocarditis
•21 deaths (12 males & 9 females)
•8 of the deaths were sudden cardiac death
autopsy -found myocarditis without prodrome
(subclinical myocarditis) all in <45 year olds who
had received mRNA vaccines
ACIP Meeting, CDC
September 19, 2025Long Term Prognosis of Myocarditis
Unknown if this will apply to COVID -19
vaccine associated myocarditisHigher risk (almost 2.5 fold) of CV death 10 years after a myocarditis diagnosis
ACIP Meeting, CDC
September 19, 2025Post Vaccine Syndrome (PVS)
•The injuries associated with PVS are prolonged, debilitating and involve diverse
symptoms and conditions, many overlapping with long COVID injuries
•Symptoms include among others dysautonomia (POTS), immune dysregulation, autoimmune disorders, severe neuropathy, cardiovascular & neurovascular injuries and severe clotting
ACIP Meeting, CDC
September 19, 2025Post Vaccine Syndrome (PVS)
•The frequency of PVS and related risk factors are currently not well understood
•Do not fit existing diagnosis codes and often have common post vaccination
symptoms but prolonged, therefore not likely to be captured by existing pharmacovigilance systems
Identification of Potential Adverse Events After COVID -19 mRNA Vaccines in Danish Children Using Healthcare Registries
ACIP Meeting, CDC
September 19, 2025mRNA Vaccines Don’t Work as Intended
•Wide biodistribution and prolonged persistent
of Spike, mRNA and nano-lipid particles
•Not understood prolonged immune response (e.g., IgG4 switch class and cytokine profile)
•Frame shift leading to production of unintended proteins and related immune
response
•DNA contamination (regulatory violation)
ACIP Meeting, CDC
September 19, 2025Vaccination in Pregnancy
Most WG members felt that the current data not only do not support recommendation
to vaccinate during pregnancy, but to the contrary support NOT to recommend:
•No appropriate randomized clinical trials to show efficacy and safety
•In the single (small) clinical trial (Pfizer) there was observed numerical imbalance of higher number of fetal anomalies among babies born to vaccinated women (8 vs. 2)
ACIP Meeting, CDC
September 19, 2025Vaccination in Pregnancy
•Observational studies are of very low -quality with structural biases, and some raise
concerns
https://pubmed.ncbi.nlm.nih.gov/36794918/
https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.17721
https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-025-07784- w
ACIP Meeting, CDC
September 19, 2025Vaccine -Specific Recommendations
The WG felt that there weren’t sufficient data and time to arrive at recommendations specific to
a vendor or a platform, but this seems likely to be a plausible approach in the future:
•In RCTs adenovirus vaccines reduced all cause mortality vs. mRNA vaccines that didn’t
https://pubmed.ncbi.nlm.nih.gov/37163200/
•Studies show Moderna may have higher protection and lower AEs compared to Pfizer
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2793236
https://www.nejm.org/doi/full/10.1056/NEJMoa2115463
•Other vaccines, including not currently authorized in the US should be evaluated
ACIP Meeting, CDC
September 19, 2025Public Trust
Members in the WG felt that there a concerning gap between CDC ‘safe and effective’
narrative and public perception that erodes trust:
•In a recent poll over 56% suspect COVID -19 vaccines caused death:
https://www.rasmussenreports.com/public_content/politics/trump_administration_second_term/56_suspect_covid_19_vaccines_caused_deaths
•In another poll, 25% think they know someone who died from COVID -19 vaccines
https://issuu.com/indiabookofrecords/docs/chugalkhor_times_mar_2023_issue_4/s/20904385
ACIP Meeting, CDC
September 19, 2025Trust of Healthcare Workers
ACIP Meeting, CDC
September 19, 2025Discussion of the Recommendations
for ACIP Vote
ACIP Meeting, CDC
September 19, 2025Recommended Updates to the Vaccine Information Statement
Most of the WG members were concerned that the existing administration processes of the
COVID -19 vaccination products do not ensure a meaningful informed consent:
ACIP Meeting, CDC
September 19, 2025Recommended Updates to the Vaccine Information Statement
“To inform is not merely to provide written or verbal notification of risks and benefits.
Information disclosures, both in their content and mode of delivery, must spur earnest
contemplation and autonomous decision-making.”
“Each VIS must have a description of a vaccine’s 1) benefits, 2) risks, 3) a statement of
availability of the VICP, and 4) any other information deemed relevant. VISs must be presented
before every vaccine dose in all clinical settings, regardless of whether there is a learned intermediary present or not.”
ACIP Meeting, CDC
September 19, 2025Recommended Updates to the Vaccine Information Statement
The WG recommendation is that the CDC engages in effort to create more
consistent and comprehensive informed consent processes, and as part of that
considers adding language accessible to patients and medical providers to
describe the following risks and uncertainties:
ACIP Meeting, CDC
September 19, 2025Recommended Updates to the Vaccine Information Statement
1.Current assessments regarding the protection provided by COVID -19
vaccines and especially seasonal COVID -19 boosters against severe
outcomes (e.g., death, hospitalization and long COVID) are of low
quality. At best, the additional protection provided by a seasonal
booster is moderate and of short duration.
ACIP Meeting, CDC
September 19, 2025Recommended Updates to the Vaccine Information Statement
2.There is evidence that repeated seasonal mRNA boosters cause
acquired changes in the immune system and may be associated with
increased vulnerability to future infections, including SARS -CoV-2 and
other respiratory viruses. These risks, as well as potential risks of autoimmunity, chronic inflammation, immune tolerance and impaired
immune surveillance including immune fatigue or suppression, are
currently not well understood.
ACIP Meeting, CDC
September 19, 2025Recommended Updates to the Vaccine Information Statement
3.There are documented deaths from symptomatic and subclinical
myocarditis, pericarditis and potentially other cardiovascular conditions
post COVID -19 vaccination, including of healthy children, with probable
causal relationship to the mRNA vaccines. This risk is likely relatively small but currently not well understood.
ACIP Meeting, CDC
September 19, 2025Recommended Updates to the Vaccine Information Statement
4.Clinical reports demonstrate that in some cases COVID -19 vaccines can
cause prolonged and debilitating post vaccine syndrome (PVS). The injuries
associated with PVS involve diverse symptoms and conditions, many overlapping with long COVID injuries. Some of the observed symptoms and conditions may include insomnia, chronic pain and fatigue, dysautonomia (e.g., POTS), immune dysregulation and deficiency, autoimmune disorders, severe neuropathy and other neurodegenerative conditions, cardiovascular and neurovascular injuries, and severe clotting. The frequency of PVS and related risk factors are currently not well understood.
ACIP Meeting, CDC
September 19, 2025Recommended Updates to the Vaccine Information Statement
5.There is evidence that in some individuals vaccinated with mRNA COVID -19
vaccines, the resulting spike protein, the mRNA and the nano- lipids
formulation components persist in different body organs, including lymph
nodes and the heart, for a prolonged period of months and possibly years in some patients. Prolonged and persistent exposure to spike, mRNA and nano- lipids particles is associated with post -vaccine syndrome (PVS) injuries
as well as potentially other side effects that are currently only partially understood.
ACIP Meeting, CDC
September 19, 2025Recommended Updates to the Vaccine Information Statement
6.The safety and the efficacy of COVID -19 vaccination during pregnancy have
never been tested in appropriately powered randomized clinical trials. In
one randomized trial there was observed numerical imbalance of higher number of babies with congenital malformation among those born to vaccinated women.
ACIP Meeting, CDC
September 19, 2025Recommendations for 2025- 2026
Guiding principles:
•Access within the FDA authorized population
•Benefits, risks and uncertainties must be communicated as part of proper informed
consent
•Debated between Individual -based decisions to group recommendations