non-infection related benefits of vaccines

 In these times of anti-science promoted by the head of the Office of Health and Human Services (RFK, Jr), I thought it was important to bring up a few studies reinforcing the non-infection-related benefits of vaccines, beyond their well-documented specific infectious disease benefits.

 

A recent very large observational South Korean study found that live zoster vaccination was associated with a lower risk of cardiovascular events for at least the next eight years (see zoster vaccine dec cardiovasc outcome EurSocCardiol2025 in dropbox or  https://doi.org/10.1093/eurheartj/ehaf230)

 

Details:

-- this nationwide, population-based cohort data-mining study included 2,207,784 individuals encompassing 98% of the South Korean population, compared individuals who had versus didn’t have live zoster vaccine but subsequently had herpes zoster (HZ) infection

    -- data were collected from a combination of the national insurance information (outpatient and inpatient data, pharmaceutical information, and death records) from the Korea Health Insurance Review and the Assessment Service, the national health examination results from the Korean National Health Insurance Service, and the live zoster vaccination data from the Korea Disease Control and Prevention Agency

-- this study included all South Korean individuals at least 50 years old who received the live zoster vaccine between January 2012 and January 2021

    -- they also included an unvaccinated control, where they applied a propensity score-based approach to those who were at least 50 years old who did not receive the live zoster vaccination (propensity scoring is a statistical method to equalize the two groups for the differences in measured baseline characteristics noted below)

    -- they did not include people who had known prior history of cardiovascular events before the vaccination, or those who had insufficient data in these large registries, thereby excluding 528,951 people

    -- total group included was 1,271,922 individuals

 

-- Baseline demographics and covariates:

    -- mean age 61 (3% were 50 to 54 years old, 25% 55 to 59 yo, 53% 60 to 64 yo, 20% at least 65 yo)

    -- 43% male, 47% living in an urban region

    -- household income: low (0-39 percentile) 29%, middle (40-79 percentile) 36%, high (80-100 percentile) 35%

    -- Charlson comorbidity index score (increased numbers reflect more comorbidities), 19 different ones are included in this index, such as heart disease, diabetes, lung disease and chronic kidney disease

    -- BMI: underweight in 27%, normal in 28%, overweight in 40%, obese in 5%

    -- smoking status: never in 69%, former in 25%, current in 6%

    -- alcohol consumption: <1 days per week in 55%, 1 to 2 days per week in 40%, 3 to 4 days per week in 3%, more days per week in 2%

    -- aerobic physical activity: at least 600 Metabolic Equivalent Task scores (METs) in 24%, less in 77%

        -- unadjusted covariates (i.e. not included in the propensity score matching):

        -- medications for diabetes in 12%, medications for hyperlipidemia in 14%, medications for hypertension in 30%

        -- blood pressure: systolic <140 mmHg and diastolic <90 mmHg in 74%; either of those cutpoints in 26%

        -- fasting glucose: <100 mg/dL in 52%, more in 48%

        -- eGFR <60 (presumably based on creatinine) in 5%, 60-89 in 52%, at least 90 in 43%

 

-- the primary outcome was the onset of cardiovascular events, comparing those who had herpes zoster infection after being vaccinated to those who were never vaccinated, as follows:

    -- cerebrovascular diseases (stroke and TIA)

    -- dysrhythmias, including atrial fibrillation, sinus tachycardia, sinus bradycardia, ventricular arrhythmias, and atrial flutter

    -- inflammatory heart disease (e.g. pericarditis and myocarditis)

    -- ischemic heart disease (e.g. acute coronary disease, MI, and angina)

    -- other cardiac disorders (e.g. heart failure, cardiac arrest, and cardiogenic shock)

    -- thrombotic disorders (e.g. arterial thromboembolism, pulmonary embolism, deep vein thrombosis)

    -- and the combination of Major Adverse Cardiovascular Events (MACE, here defined as all-cause mortality, stroke, and MI)

 

-- Observation period: 12 years

 

Results:

-- after propensity scoring, there were 635,961 individuals in both the vaccinated and unvaccinated groups

-- cardiovascular events, comparing those vaccinated vs unvaccinated:

    -- overall cardiovascular events: 23% decrease, HR 0.77 (0.76-0.78)

    -- MACE: 26% decrease, HR 0.74 (0.71-0.77)

    -- heart failure: 26% decrease, HR 0.74 (0.70-0.77)

    -- cerebrovascular disorders: 24% decrease, HR 0.76 (0.74-0.78)

    -- ischemic heart disease: 22% decrease, HR 0.78 (0.76-0.80)

    -- thrombotic disorders: 22% decrease, HR 0.78 (0.74-0.83)

    -- dysrhythmia: 21% decrease, HR 0.79 (0.77-0.81)

 

-- over 10 year followup the RMST (restricted mean survival time, a measure of the  number of days between vaccinated and unvaccinated groups, an absolute measure of survival time), difference between vaccinated and unvaccinated:

    -- ischemic heart disease: 36.63 days (36.51-36.75)

    -- dysrhythmia: 35.61 days (35.50-36.73)

    -- cerebrovascular disorders: 24.35 days (24.23–24.47)

    -- MACE: 16.51 days (16.41–16.61)

    -- other cardiac disorders: 11.19 days (11.11– 11.28)

    -- thrombotic disorders: 6.19 days (6.19–6.25) [these confidence intervals seem to be wrong, but that's what they wrote...]

more breakdown by types of cardiovascular event below, all of these associations noted above were highly statistically significant :

-- Results by stratification analysis:

    -- any cardiovascular disease following vaccination (similar patterns were found for each category of cardiovascular outcomes):

        -- males had greater benefits than females: HR 0.73 (0.71–0.74) vs HR 0.80 (0.79– 0.82); P interaction <.001

        -- age under 60 years had greater benefits than over 60 years: HR 0.73 (0.71–0.75) vs HR 0.84 (0.82–0.85); P interaction  <.001

        -- living in rural areas had greater benefits than urban areas: HR 0.75 (0.73–0.76) vs HR 0.80 (0.78–0.81); P interaction <.001

        -- low household income had greater benefits than high household income: HR 0.74 (0.72–0.76) vs HR 0.80 (0.78–0.82); P interaction <.001

        -- obesity (BMI ≥25.0) had greater benefits than lower:  HR 0.75 (0.74– 0.77) vs HR 0.79 (0.77–0.81); P interaction <.001

        -- similar patterns were found comparing individuals with healthy lifestyle habits, alcohol consumption, and sufficient physical activity vs those with unhealthy lifestyles; also for individuals using medication for diabetes, hyperlipidemia, and hypertension vs those not on medication

--the temporal pattern of lowered HR for cardiovascular outcomes following live zoster vaccination showed a U-shaped curve: most benefit in the first 5 years (the first 1-2 years post-vaccination were graphically better, but overlapping confidence intervals), then some decreasing but significant benefit up to 8 years):

    -- <1 year: HR 0.80 (0.78–0.82)

    -- 1–2 years: HR 0.74 (0.72–0.77)

    -- 2–3 years: HR 0.74 (0.71–0.76)

    -- 3–5 years: HR 0.80 (0.78–0.82)

    -- 5–8 years: HR 0.88 (0.83– 0.93)

    -- similar patterns were observed in the detailed disease categories

  

Commentary:

-- Herpes zoster (HZ) infection can occur at pretty much any age, but 2/3 occur individuals older than 49 with a lifetime risk of about 30%

-- HZ can have severe complications including long-term postherpetic neuralgia and zoster ophthalmicus, as well as increasing  high case-fatality rates in individuals aged >=65  have.

-- the live zoster vaccine has an efficacy of approximately 90%, with continued  efficacy of more than 70% for at least 10 years after vaccination

-- prior reports including relatively few patients have documented various cardiovascular events as complications of HZ infection

-- and, the CDC does recommend two doses of the vaccine in all adults at least 50 years old to prevent shingles and related complications, as well as all adults at least 19 years old who are or will be immunodeficient or immunosuppressed

-- This current Korean study had more than 2 million participants, finding:

    -- the live zoster vaccination was associated with a lower risk of cardiovascular events in those later having HZ

    -- this cardiovascular event decrease was most pronounced in the 2 to 3 years after vaccination, with diminishing but still significant differences up to eight years

    -- males, individuals less than 60 years old, individuals with healthy lifestyles, those with lower and middle incomes and rural residence seem to do particularly well in this regard

-- plausible mechanisms that could explain these findings:

    -- varicella-zoster virus can be associated with vasculopathy related to direct viral infection of the blood vessels

    -- the virus can also propagate by neural pathways, affecting both the intracranial and extracranial blood vessels

        -- hence, the virus can lead to vascular injury and cause ischemic and hemorrhagic cerebrovascular and cardiovascular events

    -- virus-related inflammation is associated with a hypercoagulable state and endovascular inflammation, potentially leading to rupture of atherosclerotic plaques and formation of thrombi, resulting in myocardial infarction as well as other thrombotic diseases

    -- the virus can involve the vagus nerve and its ganglia, potentially leading to heart failure, autonomic dysfunction, dysrhythmias and sudden cardiac death

    -- I would add to this that there are significant immunologic disruptions associated with any chronic inflammatory states: see below in the "limitations" section for more information on this.

        -- these immunologic changes from many medical (rheumatologic disease, chronic infections, etc.) and social conditions (eg, exposure to pollution, etc as per below) not identified in this analysis could potentially affect the extent of cardiovascular and other outcomes associated with the virus

-- the broad non-targeted benefits of shingles vaccine are not unique:

    -- measles vaccine is a prime example (see recent update in the prior blog: https://gmodestmedblogs.blogspot.com/2024/12/getting-rid-of-vaccines.html. In brief:

        -- measles is perhaps the most transmissible virus, with R₀ of up to 18

        -- measles was declared eradicated in the US in 2000

        -- there has been a resurgence of measles noted by the WHO in 2018; reduced vaccination has led to a 300% increase in the US since 2018

        -- historically mass measles vaccination has been associated with reduced overall childhood mortality by 30-50% in resource-poor countries and up to 90% in the most impoverished countries. this benefit could not be explained simply by preventing measles infection alone: there was a reduced mortality from non-measles causes!!

        --measles virus (MV) infection is associated with profound immunosuppression ("immune amnesia"), and recent data challenge the prior notion that this is a transient phenomenon:

            --data (mostly animal) suggest that measles infection leads to a loss in immune memory cells, and that this is prevented by vaccination

            --in macaques, measles infection leads to systemic depletion of lymphocytes and reduced innate immune cell proliferation. MV leads to replacement of "the previous memory cell repertoire with measles virus-specific lymphocytes, resulting in 'immune amnesia' to non-measles pathogens". Recovery of these memory cells requires restimulation by the appropriate antigens

        -- so, it is pretty clear that getting measles in a non-immunized individual can lead to a prolonged (non-transient) disruption of a person's prior immune response to other pathogens, that this leaves them susceptible to a recurrence of those infections, and likely that the major mortality protection by measles vaccination that leads to overall decreased all-cause mortality is related to the diffuse immune havoc created by measles virus infection

-- of course, there are multisystem effects from many infections (covid, influenza, etc.), a recent article found that really common infections with RSV in adults can have an array of cardiovascular complications (these have been known in small studies, this was a larger study with 471 patients who were hospitalized with RSV):

    -- 37% of these patients experienced cardiovascular events in the 28 day period after hospital admission (heart failure in 25%, atrial fibrillation and 13%, myocardial infarction 9%) and 44% occurred in patients with no prior history of these conditions

        -- those older than 65 who had pre-existing hypertension, heart failure, atrial fibrillation, or coronary artery disease as well as the presence of at least three cardiovascular risk factors had significantly increased risk of these events; however heart failure, AF and MI were first-time diagnoses in 46%, 30% and 54% respectively

        -- for those in the 21-day period after their RSV admission, the incidence rate ratio of cardiovascular events was 18.5 (13.7-24.9)

        -- however, even up to 6 months after that time period, the incidence rate ratio was still 1.6 (1.1-2.3), still elevated as compared to the six-month time before hospitalization (see RSV infection inc cardiovasc events ClinInfecDis2025 in dropbox, or DOI: 10.1093/cid/ciaf310)

-- and having covid wsa associated with residual long-term effects (development of long covid) months after resolution of the initial infection. for example, a UK study found that 536 patients who recovered from an acute covid infection developed long covid 6-12 months afterwards: https://gmodestmedblogs.blogspot.com/2023/04/long-covid-long-term-pathology.html, or a recent article finding that even those treated with nirmatrelvir (paxlovid) developed long covid up to 6 months later, but less long covid in high-risk patients: https://pmc.ncbi.nlm.nih.gov/articles/PMC11213188/

    -- overall covid vaccination does decrease the likelihood of long covid by about 1/2

     

Limitations:

-- there may be a selection bias for individuals who elected to get the zoster vaccine versus who decided against it. It is certainly possible that the individuals who did get the vaccine were also more keyed into a healthy lifestyle in ways that weren’t measured in this study or included in the propensity score matching

-- many of the baseline characteristics had binary cutpoints, such as physical activity, fasting blood sugar, renal function, lipids, eGFR, and hypertension and may not truly reflect the continuum of those characteristics, and this could effect the validity and generalizability of the results (ie, there really is not much difference between those who are minimally above or below theses cutpoints, creating differences that do not reflect clinical reality)

-- in addition, this group of people in South Korea had much lower prevalence of hypertension, alcohol consumption, obesity, and CKD than in many other populations, limiting generalizability of the results

-- one of the issues is whether there are fundamental differences between those individuals who get HZ infections with and without prior vaccination: it is pretty clear in the medical literature that any chronic systemic inflammation is associated with decreased immunity (https://www.nature.com/articles/s41591-019-0675-0 or for the full article in detail: https://pmc.ncbi.nlm.nih.gov/articles/PMC7147972/#:~:text=Specifically%2C%20elevated%20SCI%20can%20lead,individual's%20immuno%2Dphenotype%20in%20adulthood. the South Korean researchers did document and control for some of these (eg hypertension, diabetes, hyperlipidemia, renal dysfunction, smoking, alcohol). But there are important other causes of increased inflammation that might have affected the immune system and potentially different clinical outcomes in the effects of HZ infection, and these could affect the interpretation of their results and their generalizability:

    -- there are many problems leading to chronic inflammation, including stress, depression, air pollution, microplastics... (see https://gmodestmedblogs.blogspot.com/2023/10/update-ascvd-risk-factor-critique.html for more on this)

    -- they did have information about family income, but this is a poor surrogate marker for chronic stress: see https://gmodestmedblogs.blogspot.com/2023/01/lower-income-higher-morbidity-and_14.html for more on this, or https://www.pnas.org/doi/10.1073/pnas.1011492107 finding that high income does not improve emotional well-being

-- this study was in one country, and though impressive in its size and methodology overall, it may not be generalizable to other countries with different cultures, diet, exercise, social stresses, etc

so,

-- it is a bit painful to read articles from most other countries, where there is a single health care system, large amounts of health data for the population, large databases that allow for epidemiologic review and assessment, and very clear targets for future high quality interventional studies. and in the US we seem to be moving in the direction of even less data collection since data could undermine the efforts to track the adverse effects of current efforts to "redirect" and "deregulate" our health care system

-- this Korean study further refutes the anti-vaccine strategy of RFK, Jr the current "leader" of the US health policy, who also is targeting getting rid of the US Preventive Services Taskforce (https://www.statnews.com/2025/07/29/rfk-jr-vetting-new-members-uspstf-preventive-services-task-force/). And, as per Paul Sax's recent blog, he is stopping publication of the HIV treatment guidelines, an internationally accessed and valued guideline evaluating the most recent HIV treatment-related information

     -- these attacks on critical cornerstones of our health care system will undoubtedly lead to very serious consequences, some now and some in the future

        -- as a prescient example of the short-term effects of his approach leading to disaster, as noted in the above-mentioned blog on measles (https://gmodestmedblogs.blogspot.com/2024/12/getting-rid-of-vaccines.html), Kennedy went to Samoa, which historically had 99% vaccination levels for measles, convinced them to stop this vaccination, leading to 5707 measles cases with 83 deaths

        -- and the US so far in 2025 reports a total of 1,333 confirmed measles cases (though they note that there were many "probable" measles cases as well that were not in these numbers) in 29 outbreaks (defined as at least 3 cases that occurred this year): https://www.cdc.gov/measles/data-research/index.html [this is assuming that the statistics are accurate, given that the elimination of diversity, equity and inclusion policies might impact these results and the fact that the CDC is not able to make press releases without political review

    -- it still seems to be that we are living in a nightmare in so many ways, this one in the dismantling of essential parts of our health care system by a "leader" who has essentially no scientific understanding of healthcare. He does tote some important health issues, such as clean air, clean water, clean/healthy foods. but he is a sycophant to his boss, who is trying to undercut all of these (eg, newly being against the EPA rulings about carbon dioxide emissions)

-- and, of course, the issues noted above with cardiovascular events after severe RSV infections should prompt us clinicians and public health workers to more strongly reinforce the importance of RSV vaccinations, as well as measles, covid, the hugely important HPV vaccine in kids,.....

a brief quiz: what would you choose as your most appropriate characterization of RFK, Jr:

-- ignorant

-- ignominious

-- ignoramus

-- malevolent

   -- note: there can be more than one correct answer...

-- it is abundantly clear that we do need to give Kennedy and the Dept of Health and Human Services feedback, for which there are 3 ways:

    -- you can go to their website. though i typed in "vaccine" and got the response: "we're sorry, an error has occurred"

    -- in searching on comments to HHS, i went to the highlighted URL for the Office of Human Research Protections" which goes to a blank page

-- but, don't give up hope, on the HHS website, you can go to "submit deregulation recommendation" ......... 

geoff

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