Following the large-scale rollout of the messenger ribonucleic acid (mRNA) vaccines developed to prevent infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptomatic coronavirus disease 2019 (COVID-19), several cases of myocarditis were reported, mostly among healthy young people.
A recent study published in the journal Circulation examines the immunological picture in this scenario, looking for clues to the etiology of this rare and potentially serious complication.
Study: Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis. Image Credit: Design_Cells / Shutterstock
Introduction
The development of myocarditis following mRNA vaccination is rare, occurring in <2 per 100,000 individuals. It remains an unpredictable mysterious occurrence. Some have suggested that it is linked to the overproduction of antibodies or abnormal immune responses.
Autoantibody production due to polyclonal B cell activation and proliferation has also been suggested, as has immune complex formation and inflammation. Finally, some think that cardiac antigens closely resembling the spike protein are targeted by autoantibodies formed as a result of molecular mimicry.
The immune response to these vaccines in these patients needs to be better understood in order to determine why and how it happens. It is imperative to study the role of male hormones since young male patients are most often affected.
The researchers in this study looked at blood samples from 16 myocarditis patients, confirmed to have high levels of serum cardiac troponin T. All developed myocarditis after receiving the COVID-19 vaccine, typically within a week of the second dose. However, a few became sick after the first dose or booster dose. Over 80% were male.
They were studied by antibody profiling, including antibodies to the virus, autoantibodies or antibodies to the virome, and the analysis of T cells specifically directed against the virus. In addition, cytokine and antigen profiles were determined. These measurements were compared with those of 45 vaccinated controls, who were of similar age and health.
What did the study show?
All subjects and controls showed a rise in anti-spike antibodies and antibodies to the receptor binding domain (RBD), of all immunoglobulin (Ig) subclasses, IgA, IgM, and IgG. Functional differences were not perceived either, with Fc effector functions being similar in both categories. In short, all vaccinated individuals showed evidence of a protective immune response against the virus.
“We found no indication that a specific antibody response is associated with myocarditis.”
Additionally, these patients did not show evidence of increased autoantibody production or antibody production against other respiratory pathogens that differed in magnitude or range from the controls.
T cells of all relevant subtypes, including naïve, memory, and effector memory T cells, showed similar distributions in both groups. T cells also showed similar proportions of spike-specific memory CD4 T cells and activated CD4 and CD8 T cells. The only exceptions were the observation of small elevations in effector memory cells and PD-1-expressing bulk CD4 T cells in the myocarditis group.
The findings indicated that antibody and T-cell responses could not distinguish between post-vaccine myocarditis subjects and vaccinated controls. The only significant difference was a slight elevation in cytokine production in the former.
The exciting difference was the high level of circulating full-length spike protein in the plasma of myocarditis patients, at a mean of ~34 pg/mL. Furthermore, the protein was not bound to antibodies and remained detectable for up to three weeks from the vaccination date. In contrast, controls did not have free spike protein in their blood.
This difference could not be attributed to poor neutralizing capacity in the myocarditis group, which showed comparable neutralization relative to the control group.
Concordantly, myocarditis patients had cytokine release patterns resembling those found in multisystem inflammatory syndrome in children (MIS-C). This might indicate that the innate immune response was overactive, leading to elevations in interleukin (IL)-8, IL-10, IL-4, IL-6, tumor necrosis factor (TNF)-α, and interferon (INF)-γ relative to healthy controls. IL-8 was most closely associated with raised cardiac troponin T and antigen levels.
Alongside, leukocytes, especially neutrophils, were at higher mean levels in this group than controls, though still within normal range.
What are the implications?
The study shows that the immunological response elicited by the mRNA vaccine was very similar in those who developed post-vaccination myocarditis and others. In other words, myocarditis could not be associated with abnormal autoantibodies, viral infections other than SARS-CoV-2, or excessive production of antibodies elicited by the mRNA vaccine.
In vaccinated patients, infection with the virus was not likely to be a cause or contributing factor for myocarditis since anti-Nucleoprotein IgG was not found in these patients.
In contrast to controls, the finding of high levels of unbound full-length spike protein in myocarditis patients may point to the mechanism by which this condition arises. Similarly, MIS-C patients had circulating SARS-CoV-2 antigens.
The spike protein appears to evade immune antibodies found at normal levels in these patients, with adequate functional and neutralization capacity. The spike may damage the cardiac pericytes or endothelium, perhaps by reducing the expression of the angiotensin-converting enzyme 2 (ACE2), reducing nitric oxide production in the endothelium, or activating inflammation via integrins, causing the endothelium to become abnormally permeable.
“Thus, the spike antigen itself, which evades antibody recognition rather than invoking immune hyperactivation, may contribute to myocarditis in these individuals.”
This finding does not amount to evidence against the benefit of vaccination with these vaccines, which effectively protect against severe COVID-19 outcomes. Therefore, current vaccine recommendations are unlikely to be altered due to these results.
“Understanding the immunopathological mechanisms associated with postvaccine myocarditis will help improve safety and guide the development of future coronavirus disease 2019 (COVID-19) vaccines. These findings also suggest that administration of anti-spike antibodies, if spike antigenemia is detected, could potentially prevent or reverse postvaccine myocarditis.”
Following the large-scale rollout of the messenger ribonucleic acid (mRNA) vaccines developed to prevent infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptomatic coronavirus disease 2019 (COVID-19), several cases of myocarditis were reported, mostly among healthy young people.
A recent study published in the journal Circulation examines the immunological picture in this scenario, looking for clues to the etiology of this rare and potentially serious complication.
Study: Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis. Image Credit: Design_Cells / Shutterstock
Introduction
The development of myocarditis following mRNA vaccination is rare, occurring in <2 per 100,000 individuals. It remains an unpredictable mysterious occurrence. Some have suggested that it is linked to the overproduction of antibodies or abnormal immune responses.
Autoantibody production due to polyclonal B cell activation and proliferation has also been suggested, as has immune complex formation and inflammation. Finally, some think that cardiac antigens closely resembling the spike protein are targeted by autoantibodies formed as a result of molecular mimicry.
The immune response to these vaccines in these patients needs to be better understood in order to determine why and how it happens. It is imperative to study the role of male hormones since young male patients are most often affected.
The researchers in this study looked at blood samples from 16 myocarditis patients, confirmed to have high levels of serum cardiac troponin T. All developed myocarditis after receiving the COVID-19 vaccine, typically within a week of the second dose. However, a few became sick after the first dose or booster dose. Over 80% were male.
They were studied by antibody profiling, including antibodies to the virus, autoantibodies or antibodies to the virome, and the analysis of T cells specifically directed against the virus. In addition, cytokine and antigen profiles were determined. These measurements were compared with those of 45 vaccinated controls, who were of similar age and health.
What did the study show?
All subjects and controls showed a rise in anti-spike antibodies and antibodies to the receptor binding domain (RBD), of all immunoglobulin (Ig) subclasses, IgA, IgM, and IgG. Functional differences were not perceived either, with Fc effector functions being similar in both categories. In short, all vaccinated individuals showed evidence of a protective immune response against the virus.
“We found no indication that a specific antibody response is associated with myocarditis.”
Additionally, these patients did not show evidence of increased autoantibody production or antibody production against other respiratory pathogens that differed in magnitude or range from the controls.
T cells of all relevant subtypes, including naïve, memory, and effector memory T cells, showed similar distributions in both groups. T cells also showed similar proportions of spike-specific memory CD4 T cells and activated CD4 and CD8 T cells. The only exceptions were the observation of small elevations in effector memory cells and PD-1-expressing bulk CD4 T cells in the myocarditis group.
The findings indicated that antibody and T-cell responses could not distinguish between post-vaccine myocarditis subjects and vaccinated controls. The only significant difference was a slight elevation in cytokine production in the former.
The exciting difference was the high level of circulating full-length spike protein in the plasma of myocarditis patients, at a mean of ~34 pg/mL. Furthermore, the protein was not bound to antibodies and remained detectable for up to three weeks from the vaccination date. In contrast, controls did not have free spike protein in their blood.
This difference could not be attributed to poor neutralizing capacity in the myocarditis group, which showed comparable neutralization relative to the control group.
Concordantly, myocarditis patients had cytokine release patterns resembling those found in multisystem inflammatory syndrome in children (MIS-C). This might indicate that the innate immune response was overactive, leading to elevations in interleukin (IL)-8, IL-10, IL-4, IL-6, tumor necrosis factor (TNF)-α, and interferon (INF)-γ relative to healthy controls. IL-8 was most closely associated with raised cardiac troponin T and antigen levels.
Alongside, leukocytes, especially neutrophils, were at higher mean levels in this group than controls, though still within normal range.
What are the implications?
The study shows that the immunological response elicited by the mRNA vaccine was very similar in those who developed post-vaccination myocarditis and others. In other words, myocarditis could not be associated with abnormal autoantibodies, viral infections other than SARS-CoV-2, or excessive production of antibodies elicited by the mRNA vaccine.
In vaccinated patients, infection with the virus was not likely to be a cause or contributing factor for myocarditis since anti-Nucleoprotein IgG was not found in these patients.
In contrast to controls, the finding of high levels of unbound full-length spike protein in myocarditis patients may point to the mechanism by which this condition arises. Similarly, MIS-C patients had circulating SARS-CoV-2 antigens.
The spike protein appears to evade immune antibodies found at normal levels in these patients, with adequate functional and neutralization capacity. The spike may damage the cardiac pericytes or endothelium, perhaps by reducing the expression of the angiotensin-converting enzyme 2 (ACE2), reducing nitric oxide production in the endothelium, or activating inflammation via integrins, causing the endothelium to become abnormally permeable.
“Thus, the spike antigen itself, which evades antibody recognition rather than invoking immune hyperactivation, may contribute to myocarditis in these individuals.”
This finding does not amount to evidence against the benefit of vaccination with these vaccines, which effectively protect against severe COVID-19 outcomes. Therefore, current vaccine recommendations are unlikely to be altered due to these results.
“Understanding the immunopathological mechanisms associated with postvaccine myocarditis will help improve safety and guide the development of future coronavirus disease 2019 (COVID-19) vaccines. These findings also suggest that administration of anti-spike antibodies, if spike antigenemia is detected, could potentially prevent or reverse postvaccine myocarditis.”
Retsef Levi, a former Israeli military intelligence officer, an expert in risk management and health systems, and a professor at The Massachusetts Institute of Technology Sloan School of Management, coauthored a paper that found a 25 percent rise in heart attack emergency calls among young Israelis after the country’s rollout of the COVID genetic vaccine.
Levi argues that there is enough data from this and various other studies on the vaccine’s adverse heart effects, to stop its use and run a thorough investigation into why many once-healthy young people suffer or die from heart inflammation after being vaccinated.
“The main question that we need to ask ourselves is, do we have enough evidence from this study and many other studies, to say halt!” Levi said during a recent interview with Epoch TV’s “American Thought Leaders” program. “We’re going to stop these vaccines, for young individuals, but maybe overall, and we’re going to take the time to really look very, very carefully and scrutinize every piece of data and bring together every possible piece of data to understand what is the answer.”
Levi has worked extensively in the areas of analytics and modeling, looking at issues of risk management in the field of healthcare and other related systems. Mainly, analyzing data sets to see what they reveal about quality, safety, risks, etc.
His coauthored paper in Nature Scientific Reports looked at Israel’s national emergency calls in the first five months of 2021 and found a 25 percent increase in cardiac arrest and heart attacks in men aged 16-39 as compared to the year before the national vaccine rollout.
The study found, “a temporal correlation between this increase starting in early 2021, and the launch of the vaccination campaign in Israel,” said Levi.
The paper does not conclude a causal relationship between the vaccine and the observed increase in heart problems, but it definitely gives enough evidence to warrant an in-depth investigation said, Levi.
Further, Israel’s health ministry should want to know why there was an increase in heart problems; but instead, they “launched an attack on us, both in the public domain, as well as even actively trying to approach the journal and asked the journal to retract the paper,” said Levi.
An artist rendering of a heart and SARS-CoV-2 virus particles. (By Lightspring)
Sound Scientific Process Abandoned
There is a lot of data that strongly suggests an increase in myocarditis or death in young people who have been vaccinated. Levi believes that the haste with which the vaccines were produced, approved, and deployed, neglected safety and best practices for rolling out vaccines.
This deviation from basic sound scientific principles has put health officials in Israel and the United States, “in a situation where you essentially cannot admit any wrong anymore because that will imply that you did something very, very disastrous,” said Levi. “We approve it in a very expedited way, and we approve it to everybody regardless of the risk, and that was basically the fundamental mistake that we’ve done. And I think everything else can be explained by that.”
There was strong early evidence, including a 2020 study done by Stanford University researchers John Ioannidis and colleagues concluding that people under 65, with no comorbidities, had very little risk of death from COVID-19 and should have helped target vaccines to the high-risk populations.
Levi believes health agency officials and governments should not have required vaccinations for healthy young people, and by doing so, “put them in a situation when they take an unknown risk that now we know is actually, in some cases pretty substantial, and could really compromise the future of young people and including causing their death.”
Florida Surgeon General Dr. Joseph Ladapo. (York Du/The Epoch Times)
Mounting Evidence Against Vaccinating Youth
Florida Surgeon General Dr. Joseph Ladapo, recently advised Floridians not to vaccinate healthy young people, because he found an 84 percent increase in heart problems among young men. While his study also does not prove a causal relationship, “at the very least, this should just raise your concerns that something really, really disturbing is happening here,” said Levi.
Levi thinks the public should look at a variety of studies when determining the safety of any vaccine or health guidance, and that Ladapo’s findings are in keeping with a large body of evidence that supports his guidance, even though the mainstream is dismissing this evidence.
Levi believes Ladopo was correctly following the mounting evidence of vaccine-related heart problems and deaths, and the principle of “do no harm.” “Ladopo was saying, I don’t feel comfortable to continue to give these vaccines to young individuals, given the evidence that I have,” said Levi.
Fear Is Destroying Health Systems
“I actually think that the regulatory agencies, with the support of some scientists in the media, are essentially representing a very extreme approach and a very dangerous approach, if I may say, because again, they are undermining the fundamentals of proper scientific and medical work,” said Levi. “And I’m very, very concerned about the future of science, the future trust in science and medicine.”
Fear has caused many people to make poor decisions said, Levi. “What I realized is that in many cases, it [fear] shuts down intellect, rationale, ethics, [and] scared people can do very, very bad things to each other.”
This fear caused health officials to abandon reason and prevented them from looking at the whole health of an individual, including the mental, emotional, and physical aspects, especially in the case of young people said, Levi.
Consequently, young people have been deeply affected, with among other things, a loss of education, weight gain, increased anxiety, and depression, much of which could have been prevented had leaders used a holistic and science-based approach to mitigating the threats of the pandemic, Levi said.
A cyclist with a trailer for children passes a “Beach Closed” sign on the boardwalk in Miami Beach, Fla., on March 22, 2020. (Cliff Hawkins/Getty Images)
We have failed our children, said Levi.
“And to me, that’s not only a scientifical scientific flaw, but this is also an ethical flaw. This is an ethical failure, that as a society, we then [did not] put the young and the children as a top priority. That, to me, that’s what the society is supposed to do.”
The lockdown protocol used around the world failed miserably, especially in China said, Levi.
“What is striking to me is that freedom is a fundamental value of democratic societies, but it’s also a fundamental value of science,” but was largely ignored, said Levi.
Instead, those in democratic societies used the most draconian policies to take away fundamental freedoms and in the scientific realm, people were “essentially imposing censorship mechanisms that I’ve never seen, in my over 16 years as a scientist, I’ve never seen something close to that,” said Levi.
A medical worker prepares to give 62-year-old Moshe Geva Rosso a fourth dose of the COVID-19 vaccine, at Sheba Medical Center in Ramat Gan, Israel, on Dec. 31, 2021. (Nir Elias/Reuters)
Israel’s Vaccine Monitoring
“The Ministry of Health (MOH) in Israel, is actively hiding critical information about side effects of the vaccines from the Israeli public,” said Levi. In addition, the health ministry did not have a functional monitoring system for vaccine adverse effects until recently.
This is a critically important fact because Israel has been at the forefront of requiring their citizens to get vaccinated and boosted, having signed a contract with Pfizer early on in the pandemic, “that essentially made Israel a worldwide lab for the rest of the world,” said Levi.
Israel only started to broadly monitor adverse side effects at the end of 2021, and hired a team to research what they found regarding adverse effects, which is why they leaked a video showing Israel’s health ministry discussing the issue, said Levi.
The Israeli MOH commissioned researchers to analyze adverse event reports submitted by Israelis. The researchers presented findings from the new surveillance system at an internal June meeting, video footage of which was obtained by an Israeli journalist. This research team’s findings are contrary to the health ministry’s claim that the adverse events, if any, are short-term.
Many of the side effects are in fact, not short term. These health problems, “actually last weeks, months, and sometimes over a year. When I say side effects, I talk about menstrual irregularities, I talk about serious neurological side effects, and so forth,” said Levi.
In these videos, the team of researchers is heard advising the Israeli health ministry to use caution when speaking to the public about the vaccines’ adverse health effects.
“It seems that the Ministry of Health in Israel took this to their attention because when you look at the actual report that they post in the public domain, they essentially took out a lot of the messages, a lot of the findings that were found by the research team that they hired. And moreover, they misrepresented the data, and misrepresented the reporting rates of the different side effects and made them look like very, very rare,” said Levi.
The reports that the ministry put up for the Israeli public to see were clearly manipulated said, Levi.
“And essentially, these reports are representing only six months out of a year and a half, and only 15 to 17 percent of the population in Israel, rather than the entire population and all the doses that were given in Israel.”
The Epoch Times reached out to Israel’s MOH for comment but had not receive a reply before publishing time.
Rechallenge
“So, now I have a situation when every time they take the vaccine I see the same response, that is called rechallenge,” said Levi. A positive rechallenge was reported in 10 percent of the women who complained of menstrual issues, according to the researchers, who also identified cases of rechallenge for other adverse events.
The phenomenon of rechallenge—when adverse events reoccur or worsen following additional vaccine doses—proved that some of the events were caused by the vaccine, researchers said.
Dr. Sharon Alroy-[Preis], who is the number two healthcare official in the Ministry of Health, when interviewed on Israeli TV said the adverse reactions that women are facing with things like menstrual irregularities were fleeting, and of no great concern.
“In fact, there are women that suffer from weeks and months, and over a year sometimes, of irregular menstrual cycles and different types of irregularities,” said Levi. “And there is no acknowledgment from anybody in the Ministry of Health, there is no acknowledgment that I’m aware of, from any health authority or health agency in the world, [that] hey, there is a problem here.”
Eroded Trust
“And the worst thing is they ignore the voice of the patient.”
Public health agencies around the world, including the United States and Israel, have not been transparent about the vaccines and the adverse events from the shots, said Levi, to such an extent that it takes a lawsuit to get the data they have collected.
The public should be told, “what is the impact of these vaccines on all-cause mortality and other health outcomes in a way that is informative, so that people can make their risk-benefit decision based on their age, health background, beliefs, whatever. But this is unheard of that health agencies behave in a way that you need to take them to court to release data,” said Levi.
These agencies need to return to basic principles of transparency and empathy, fundamental to public health, in order to eliminate the mistrust created by the lack of honesty during the pandemic.
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Jan Jekielek is a senior editor with The Epoch Times and host of the show, “American Thought Leaders.” Jan’s career has spanned academia, media, and international human rights work. In 2009 he joined The Epoch Times full time and has served in a variety of roles, including as website chief editor. He is the producer of the award-winning Holocaust documentary film “Finding Manny.”
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Masooma Haq began reporting for The Epoch Times from Pakistan in 2008. She currently covers a variety of topics including U.S. government, culture, and entertainment.
Data on medium-term outcomes in indivduals with myocarditis after mRNA COVID-19 vaccination are scarce. We aimed to assess clinical outcomes and quality of life at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults.
Methods
In this follow-up surveillance study, we conducted surveys in US individuals aged 12–29 years with myocarditis after mRNA COVID-19 vaccination, for whom a report had been filed to the Vaccine Adverse Event Reporting System between Jan 12 and Nov 5, 2021. A two-component survey was administered, one component to patients (or parents or guardians) and one component to health-care providers, to assess patient outcomes at least 90 days since myocarditis onset. Data collected were recovery status, cardiac testing, and functional status, and EuroQol health-related quality-of-life measures (dichotomised as no problems or any problems), and a weighted quality-of-life measure, ranging from 0 to 1 (full health). The EuroQol results were compared with published results in US populations (aged 18–24 years) from before and early on in the COVID-19 pandemic.
Findings
Between Aug 24, 2021, and Jan 12, 2022, we collected data for 519 (62%) of 836 eligible patients who were at least 90 days post-myocarditis onset: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both surveys. Median patient age was 17 years (IQR 15–22); 457 (88%) patients were male and 61 (12%) were female. 320 (81%) of 393 patients with a health-care provider assessment were considered recovered from myocarditis by their health-care provider, although at the last health-care provider follow-up, 104 (26%) of 393 patients were prescribed daily medication related to myocarditis. Of 249 individuals who completed the quality-of-life portion of the patient survey, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (20%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with depression. Mean weighted quality-of-life measure (0·91 [SD 0·13]) was similar to a pre-pandemic US population value (0·92 [0·13]) and significantly higher than an early pandemic US population value (0·75 [0·28]; p<0·0001). Most patients had improvements in cardiac diagnostic marker and testing data at follow-up, including normal or back-to-baseline troponin concentrations (181 [91%] of 200 patients with available data), echocardiograms (262 [94%] of 279 patients), electrocardiograms (240 [77%] of 311 patients), exercise stress testing (94 [90%] of 104 patients), and ambulatory rhythm monitoring (86 [90%] of 96 patients). An abnormality was noted among 81 (54%) of 151 patients with follow-up cardiac MRI; however, evidence of myocarditis suggested by the presence of both late gadolinium enhancement and oedema on cardiac MRI was uncommon (20 [13%] of 151 patients). At follow-up, most patients were cleared for all physical activity (268 [68%] of 393 patients).
Interpretation
After at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination, most individuals in our cohort were considered recovered by health-care providers, and quality of life measures were comparable to those in pre-pandemic and early pandemic populations of a similar age. These findings might not be generalisable given the small sample size and further follow-up is needed for the subset of patients with atypical test results or not considered recovered.
Funding
US Centers for Disease Control and Prevention.
Introduction
Evidence from the USA and multiple international vaccine safety monitoring systems support a small but increased risk of myocarditis after mRNA COVID-19 vaccination.
1
WHO COVID-19 subcommittee of the World Health Organization Global Advisory Committee on Vaccine Safety: updated guidance regarding myocarditis and pericarditis reported with COVID-19 mRNA vaccines.
In 2021, data from the Vaccine Adverse Event Reporting System (VAERS) indicated that in US individuals aged 12 years or older, approximately 4·8 cases of myocarditis per million doses of mRNA COVID-19 vaccines administered were reported, with the highest reporting rates in those aged 12–29 years.
2
Gargano JW
Wallace M
Hadler SC
et al.
Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June, 2021.
Despite the higher than expected occurrence of myocarditis after COVID-19 vaccination, the benefits of mRNA COVID-19 vaccines have been shown to outweigh the risk of myocarditis.
2
Gargano JW
Wallace M
Hadler SC
et al.
Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June, 2021.
,
3
Block JP
Boehmer TK
Forrest CB
et al.
Cardiac complications after SARS-CoV-2 infection and mRNA COVID-19 vaccination—PCORnet, United States, January, 2021–January, 2022.
Research in context
Evidence before this study
In December, 2020, the US Food and Drug Administration (FDA) issued emergency use authorisations (EUAs) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine and the Moderna COVID-19 (mRNA-1273) vaccine. In May, 2021, FDA expanded the EUA for the BNT162b2 vaccine to include adolescents aged 12–15 years. By July, 2022, more than 200 million people in the USA had received two doses of a COVID-19 mRNA vaccine and more than 1500 cases of myocarditis with onset after mRNA COVID-19 vaccination were reported to the Vaccine Adverse Events Reporting System (VAERS). We searched PubMed for articles published up to April 30, 2022, using the keywords “mRNA vaccine” and “myocarditis”, without any language restrictions. Systematic reviews published in 2022 included more than 5299 individuals with myocarditis after mRNA vaccination and suggested the risk was highest in adolescents and young males after a second vaccine dose. Findings from these systematic reviews suggest that most cases of myocarditis after mRNA COVID-19 vaccination have resolution of symptoms at or soon after discharge from a short hospital stay. However, data on medium-term prognoses for adolescents and young adults diagnosed with myocarditis after mRNA COVID-19 vaccination are scarce.
Added value of this study
To our knowledge, this is the largest evaluation of outcomes among patients diagnosed with myocarditis after mRNA COVID-19 vaccination, with follow-up at least 90 days since onset. We collected data from both patients (or their parents or guardians) and health-care providers, and evaluated a comprehensive range of outcomes, including follow-up cardiac biomarkers, cardiac magnetic resonance imaging, echocardiograms, troponin levels, and electrocardiograms. We found that 320 (81%) of 393 patients with a health-care provider assessment were considered recovered from myocarditis, and quality of life measures were similar to pre-pandemic or early pandemic measurements. No single diagnostic test or clinical feature appeared to be associated with recovered status.
Implications of all the available evidence
Myocarditis after mRNA COVID-19 vaccination is rare, but potentially serious. To better understand possible longer term sequalae of myocarditis, continued follow-up is important, particularly for the patients not recovered by at least 90 days since symptom onset. Vaccination remains the most effective way of preventing morbidity and mortality from COVID-19.
Cardiac assessment of patients diagnosed with myocarditis after mRNA COVID-19 vaccination often shows increased cardiac biomarkers (eg, troponin concentrations) and atypical cardiac imaging (eg, echocardiograms), which are similar findings to those shown for viral or acute myocarditis.,
5
Oster ME
Shay DK
Su JR
et al.
Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December, 2020 to August, 2021.
Viral myocarditis unrelated to mRNA COVID-19 vaccination can lead to heart failure, cardiac transplantation, or death.
6
Ghelani SJ
Spaeder MC
Pastor W
Spurney CF
Klugman D
Demographics, trends, and outcomes in pediatric acute myocarditis in the United States, 2006 to 2011.
Conversely, case descriptions suggest that clinical outcomes following a diagnosis of myocarditis after mRNA COVID-19 vaccination are more favourable than those associated with viral myocarditis, with resolution of symptoms often described at or soon after discharge from a short hospital stay for myocarditis after mRNA COVID-19 vaccination.
5
Oster ME
Shay DK
Su JR
et al.
Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December, 2020 to August, 2021.
,
7
Sinagra G
Anzini M
Pereira NL
et al.
Myocarditis in clinical practice.
,
8
Witberg G
Barda N
Hoss S
et al.
Myocarditis after COVID-19 vaccination in a large health care organization.
,
9
Truong DT
Dionne A
Muniz JC
et al.
Clinically suspected myocarditis temporally related to COVID-19 vaccination in adolescents and young adults: suspected myocarditis after COVID-19 vaccination.
However, data on follow-up prognoses for adolescents and young adults diagnosed with myocarditis after mRNA COVID-19 vaccination are scarce.
10
Amir G
Rotstein A
Razon Y
et al.
CMR imaging 6 months after myocarditis associated with the BNT162b2 mRNA COVID-19 vaccine.
,
11
Fronza M
Thavendiranathan P
Karur GR
et al.
Cardiac MRI and clinical follow-up in COVID-19 vaccine-associated myocarditis.
,
12
Jain SS
Steele JM
Fonseca B
et al.
COVID-19 vaccination-associated myocarditis in adolescents.
To conduct surveillance, the US Centers for Disease Control and Prevention (CDC) developed a working myocarditis case definition with a team of subspecialists that has been used in several studies.
2
Gargano JW
Wallace M
Hadler SC
et al.
Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June, 2021.
,
5
Oster ME
Shay DK
Su JR
et al.
Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December, 2020 to August, 2021.
,
9
Truong DT
Dionne A
Muniz JC
et al.
Clinically suspected myocarditis temporally related to COVID-19 vaccination in adolescents and young adults: suspected myocarditis after COVID-19 vaccination.
,
13
Goddard K
Lewis N
Fireman B
et al.
Risk of myocarditis and pericarditis following BNT162b2 and mRNA-1273 COVID-19 vaccination.
In August, 2021, the CDC began follow-up of myocarditis cases to describe medium-term outcomes in the age group with the highest risk of myocarditis after mRNA COVID-19 vaccination diagnosis (ie, individuals aged 12–29 years). We report findings of clinical outcomes and quality of life at least 90 days since the onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults aged 12–29 years.
Results
Between Jan 12 and Nov 5, 2021, 989 cases of myocarditis after mRNA COVID-19 vaccination in patients aged 12–29 years were reported to VAERS and met the CDC’s case definition for myocarditis. Of these, 836 (85%) patients were at least 90 days post-myocarditis onset (figure 1). Of the 836 patients, 204 (24%) patients had no telephone number available for contact and 257 (31%) patients were unreachable. Of the remaining 375 patients, 357 (95%) patients consented to the survey and 18 (5%) patients declined. Between Aug 24, 2021, and Jan 12, 2022, we contacted and collected data for 519 (62%) of the 836 eligible patients: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both the patient and health-care provider survey (figure 1). Median interval from myocarditis onset to survey completion was 143 days (IQR 131–162) for patients and 191 days (170–216) for health-care providers. We found no significant differences in VAERS reporter type (health-care provider or patient), geographical census region, age, sex, initial echocardiogram findings, or race or ethnicity in patients surveyed compared with patients who were not surveyed (appendix 1 p 8). In a subset of patients with abnormal echocardiograms, the abnormality identified was a left ventricular ejection fraction (LVEF) of less than 50%. Of the 100 survey respondents with LVEF values recorded at their initial diagnosis, 33 (33%) had LVEF values less than 50%, which was not statistically different from the results in non-respondents (27 [42%] of 65 non-respondents; χ2=1·24, p=0·265).
Figure 1Survey participation of patients with myocarditis after mRNA COVID-19 vaccination reported to VAERS at least 90 days since symptom onset
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CDC=US Centers for Disease Control and Prevention. VAERS=Vaccine Adverse Event Reporting System.
For 393 (47%) of 836 patients, health-care providers were contacted; 241 (61%) of 393 were cardiologists. At the time of the survey, health-care providers considered 320 (81%) of 393 patients to be recovered: 261 (66%) patients were considered fully recovered and 59 (15%) patients were considered to be probably recovered but awaiting further information. An additional 61 (16%) patients had improved and four patients had the same cardiac status as at the initial myocarditis diagnosis; these 65 patients were categorised as not fully recovered (figure 1). The cumulative proportion of patients considered recovered in the time (weeks) since the last health-care provider encounter is shown in appendix 1 (p 15). The median time from myocarditis symptom onset to the last health-care provider encounter for patients who were considered probably fully recovered or fully recovered was 92 days (IQR 43–133), and for patients who were considered fully recovered the median time was 84 days (36–135).
Most patients were male (457 [88%] of 519 patients) and White non-Hispanic (274 [53%]), and the median age of all patients was 17 years (IQR 15–22; table 1). 98 (19%) of 519 patients were Hispanic of any race. There was no notable difference between recovered individuals compared with individuals who were not recovered across any ethnic or racial groups. Overall, patients considered to be recovered and not recovered from myocarditis were similar with respect to age (median age 17 years [IQR 15–21] for patients considered recovered vs 17 years [15–21] for those considered not recovered) and sex (290 [91%] male individuals who were considered recovered vs 56 [86%] of male individuals who were considered not to be recovered, and 30 [9%] female individuals who were considered recovered vs 9 [14%] of female individuals who were not considered recovered). The median time from illness onset to health-care provider interview for the 320 (81%) of 393 individuals who were considered recovered was 189 days (IQR 167–214), and for the 61 (16%) of 393 patients who were considered improved but not fully recovered the median time was 195 days (179–195).
Table 1Demographic characteristics and symptoms of patients by provider-reported recovery status from myocarditis after mRNA COVID-19 vaccination
Data are n (%) unless specified otherwise. Data are based on the completion of 357 patient surveys, 393 provider surveys, and 231 linked surveys, resulting in 519 patients for which data were collected. Health-care provider determination of patient myocarditis recovery was provided for 393 patients, of whom 320 were considered fully or probably fully recovered and 65 were not considered recovered (and eight patients had an undetermined recovery status; figure 1). Based on the last patient encounter, health-care providers reported that 62 (16%) of 393 patients had at least one symptom that might occur with myocarditis.
In the 2 weeks before the survey date, 178 (50%) of 357 patients reported having at least one symptom that might occur with myocarditis (chest pain or discomfort, fatigue, shortness of breath, or palpitations). Patients who were not considered recovered from myocarditis more frequently reported fatigue than did patients who were considered recovered (12 [43%] vs 40 [21%]; p=0·018; table 1). By contrast, based on the last patient encounter, health-care providers reported that 62 (16%) of 393 patients at least one symptom that might occur with myocarditis (table 1).
Of 357 patients surveyed, 267 (75%) were enrolled in school or in paid employment; 43 (16%) of whom reported missing school or workdays in the 2 weeks before the survey date. Of those 43 patients, 15 (35%) believed it was associated with myocarditis.
Of 357 patients surveyed, 249 (71%) consented to completing both the EQ-5D-5L and EQ-VAS components of the patient survey. Of 249 patients, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (21%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with anxiousness or depression (figure 2A). Overall, patients reported having good health, reflected by the high median weighted index score (0·94; IQR 0·88–1·00) and median overall health status (EQ-VAS) score (90; 80–95; figure 2B, C).
Figure 2Self-assessment of health-related quality of life among patients with myocarditis after mRNA COVID-19 vaccination
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(A) Bar plot of health-related quality of life among patients. Patients were administered the EuroQol 5-dimension 5-severity level questionnaire; for analysis, the five health-related dimensions were dichotomised into the frequency of problems (severity levels 2–5) and no problems (level 1). (B) Violin plot of weighted quality of life measure (using value weights in appendix 1 p 7) converted from each patient health profile from (A) to an index score between 1 (perfect health) and 0 (equivalent to death). (C) Violin plot of patient self-assessed overall health on a scale from 0 to 100 (with 100 representing best possible health and 0 representing the worst possible health). The denominator for the EuroQol questionnaire was 249 respondents. In the violin plots (B, C), the limits of the boxes denote IQR and the horizontal line denotes median values. Whisker endpoints are equal to the maximum and minimum values below or above the median plus or minus 1·5 times the IQR. The width of the outer shape around the box plots indicates the probability density of values or responses with a given result.
The mean EQ-5D-5L weighted utility score in our group (0·91 [SD 0·13]) was significantly higher than that for US respondents aged 18–24 years who completed a EQ-5D-5L questionnaire during the pandemic, as reported by Hay and colleagues
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
(0·75 [0·28]; p<0·0001). Mean EQ-5D-5L weighted utility scores from the pre-pandemic timepoint among US respondents aged 18–24 years have also been reported by Jiang and colleagues, from face-to-face surveys and online surveys.
23
Jiang R
Janssen MFB
Pickard AS
US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.
The weighted score from our survey was not significantly different to that obtained in the face-to-face surveys (0·92 [0·13]), but our score was significantly higher than that from the online surveys (0·84 [0·18]; p<0·0001).
Most patients were admitted to hospital after an initial diagnosis of myocarditis (484 [93%] of 519 patients). Of these 484 patients, 393 (81%) patients had information on level of care, according to the health-care provider surveys; 99 (25%) of these 393 patients were treated in an intensive care unit and one (<1%) patient required extracorporeal membrane oxygenation (table 2). To our knowledge, no deaths occurred during follow-up among the patients eligible for the survey. Six (2%) of 357 patients who self-reported re-admission to hospital had a hospital admission because of an adverse event after myocarditis treatment (n=3; adverse reactions to intravenous immune globulin) or had any cardiac abnormality identified (n=3; appendix 1 p 6); all patients were discharged within 1 week.
Table 2Level of care, testing, and treatment by recovery status among patients with myocarditis after mRNA COVID-19 vaccination
Data are n (%) unless otherwise specified. Data are based on the completion of 393 health-care provider surveys. Health-care provider determination of patient myocarditis recovery was provided for 393 patients, of whom 320 were considered fully or probably fully recovered, 65 were not considered recovered, and the health-care provider was unsure of the recovery status in eight patients, as shown in figure 1. Follow-up cardiac testing was performed, although the result of the test was not available for troponin concentration in three patients, echocardiogram in five patients, cardiac MRI in seven patients, exercise stress testing in five patients, and ambulatory rhythm monitoring in nine patients.
At follow-up, fewer patients had restrictions on physical activity than at initial diagnosis, and 34 (52%) of 65 individuals with restrictions on physical activity at the time of follow-up who were not considered recovered were cleared for all physical activity; 31 (48%) individuals still had restrictions (table 2). Median interval from myocarditis onset to approval for all physical activity was 98 days (IQR 57–134; table 2).
104 (26%) of 393 patients were prescribed daily medications related to myocarditis at the last health-care provider encounter (table 2). Patients who were not considered recovered from myocarditis were more frequently prescribed daily medication than were patients who were considered to be recovered. The most prescribed medications, as of the last health-care provider follow-up, were colchicine, β-blockers, and non-steroidal anti-inflammatory drugs (table 2).
At follow-up, most patients had improvements in diagnostic marker and imaging data, including normal or back-to-baseline troponin concentrations, echocardiograms, exercise stress testing, ambulatory rhythm monitoring, and electrocardiograms (figure 3). In the ten patients with abnormal ambulatory rhythm monitoring results, we found eight (80%) had atrial, supraventricular, or ventricular arrhythmia, three (30%) had a conduction delay or block, and five (50%) had frequent atrial or ventricular ectopy. Of these 10 patients, three (30%) had evidence of late gadolinium enhancement on follow-up cardiac MRI; of the three with evidence of late gadolinium enhancement, two (67%) had evidence of an atrial, supraventricular, or ventricular arrhythmia. Among the 151 patients who had cardiac MRIs during outpatient follow-up, 81 (54%) patients had one or more abnormalities. Abnormal cardiac MRI findings included the presence of late gadolinium enhancement (71 [47%] patients), inflammation or oedema (22 [15%] patients), or wall motion abnormalities (six [4%] patients; figure 3, appendix 1 p 9). Evidence of ongoing myocarditis, defined by both late gadolinium enhancement and oedema using modified Lake Louise criteria,
25
Ferreira VM
Schulz-Menger J
Holmvang G
et al.
Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations.
was uncommon (20 [13%] of 151 patients; appendix 1 p 9). Median interval from symptom onset to evidence of ongoing myocarditis was 26 days (IQR, 9–94) and from symptom onset to evidence of late gadolinium enhancement was 109 days (58–163; appendix 1 p 10). Of the 67 patients with late gadolinium enhancement or evidence of ongoing myocarditis, additional follow-up testing indicated abnormal echocardiograms in five (7%) patients, abnormal troponin concentrations in five (7%) patients, and abnormal electrocardiograms in 14 (21%) patients (appendix 1 p 13).
Figure 3Follow-up functional status, biomarker testing, and cardiac imaging in patients at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination
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Cardiac biomarker testing or imaging findings are from the health-care provider surveys completed for 393 patients. Not all patients received diagnostic testing or imaging and the denominator for each follow-up test is equal to the sum of the normal and abnormal findings; the type of abnormalities identified are not mutually exclusive.
In the subset of patients with abnormal findings at the time of myocarditis diagnosis, abnormal diagnostic markers or abnormal imaging were also observed at follow-up in seven (12%) of 60 with initial abnormal echocardiograms, 19 (5%) of 387 with initial elevated troponin levels, and 47 (32%) of 146 with initial abnormal cardiac MRIs (figure 4). There was substantial heterogeneity in cardiac biomarkers, imaging, and patient functional status between patients considered recovered or not recovered from myocarditis (appendix 1 p 16). All cardiac test results (ie, echocardiogram, electrocardiogram, cardiac MRI, and troponin) were available for follow-up review in only 199 (62%) of 320 patients considered recovered, 44 (68%) of 65 considered not recovered, and three (38%) of eight with an unknown recovery status.
Figure 4Changes in cardiac biomarker and imaging from the initial encounter and the health-care provider follow-up
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Testing, including echocardiograms, cardiac MRIs, and troponin concentrations, performed at the time of initial myocarditis diagnosis and at follow-up are not necessarily matched because each patient had testing (or not) at the discretion of the treating health-care providers.
Discussion
We ascertained outcomes at least 90 days since onset of myocarditis among 519 patients aged 12–29 years who received an mRNA COVID-19 vaccination and met the CDC case definition for myocarditis. Most (81%) patients for whom a follow-up health-care provider survey was completed were considered recovered from myocarditis, and most self-reported overall good health on the EQ-5D-5L. Readmissions to hospital were uncommon, and no deaths were identified during the follow-up period. Myocarditis after mRNA COVID-19 vaccination is rare yet potentially serious, and although most patients were considered recovered by health-care providers at least 90 days since onset, nearly half of patients continued to self-report symptoms, including chest pain, and a quarter were prescribed daily cardiac medications. These findings suggest that continued follow-up and assessment of myocarditis after mRNA COVID-19 vaccination is needed to more fully understand recovery after vaccine-associated myocarditis.
From a clinical standpoint, our findings suggest that myocarditis after mRNA COVID-19 vaccination could have a more favourable prognosis than myocarditis after viral infection, based on data available from the pre-COVID-19 period. In a published study of outcomes in children within 90 days of viral or acute myocarditis onset in the USA, 119 (23%) of 514 individuals required extracorporeal membrane oxygenation or a ventricular-assisted device and 58 (11%) of 514 individuals required cardiac transplant or died.
6
Ghelani SJ
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Klugman D
Demographics, trends, and outcomes in pediatric acute myocarditis in the United States, 2006 to 2011.
In a recent nationwide study in Denmark of adults, 90-day all-cause mortality among those with acute myocarditis was 4·9%.
26
Kragholm KH
Lindgren FL
Zaremba T
et al.
Mortality and ventricular arrhythmia after acute myocarditis: a nationwide registry-based follow-up study.
A longer term follow-up study of acute myocarditis among older adults (median age 34 years [IQR 24–42]) in Italy observed cardiac mortality or heart transplant rates at 1 year and 5 years of 3·0% and 4·1%, respectively, although complicated cases had rates of adverse cardiac outcomes that were several times higher.
27
Ammirati E
Cipriani M
Moro C
et al.
Clinical presentation and outcome in a contemporary cohort of patients with acute myocarditis: multicenter Lombardy registry.
In contrast with these studies, we found that only four (1%) patients had the same cardiac status as at the initial myocarditis diagnosis (ie, did not improve but did not worsen), whereas more than 95% (381 of 393 patients) showed improvement or recovery. Consistent with our findings, a recent report comparing classic myocarditis to COVID-19 vaccine-related myocarditis in individuals aged younger than 21 years observed similar clinical presentations and found COVID-19 vaccine-related myocarditis had better outcomes and a more rapid cardiac recovery.
28
Patel T
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West Z
et al.
Comparison of multisystem inflammatory syndrome in children-related myocarditis, classic viral myocarditis, and COVID-19 vaccine-related myocarditis in children.
Published data for health-related quality of life in the USA among individuals aged 18–24 years, before the COVID-19 pandemic, showed that 45 (42%) of 107 individuals reported anxiety or depression and 35 (33%) of 107 individuals reported pain or discomfort.
23
Jiang R
Janssen MFB
Pickard AS
US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.
More recent quality of life measure data from Hay and colleagues
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
among US respondents during the early stages of the COVID-19 pandemic showed that 1653 (60·2%) of 2746 individuals reported anxiety or depression.
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
Consistent with these observations, we found that patients with myocarditis after mRNA COVID-19 vaccination reported similar or better quality of life measures than the general US population, with fewer patients with myocarditis reporting anxiety or depression than did individuals during the pandemic (46% [114/249] vs 60·2% [1653/2746]). However, absence of age-specific data in the previous analyses
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
,
23
Jiang R
Janssen MFB
Pickard AS
US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.
precluded any further statistical comparisons in this study.
Despite clinical improvements and normalisation of most diagnostic test results, as noted by health-care providers, half of patients (178/357) surveyed continued to report at least one symptom potentially associated with myocarditis after COVID-19 vaccination. One possible explanation for the persistence of symptoms is that approximately 50% of patients reported depression or anxiety, conditions that can manifest as symptoms associated with myocarditis, such as chest pain or palpitations.
29
Lipsitz JD
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Apfel H
et al.
Anxiety and depressive symptoms and anxiety sensitivity in youngsters with noncardiac chest pain and benign heart murmurs.
The meaning of the cardiac MRI findings among the subset of patients who received cardiac imaging is unclear. Evidence of ongoing myocarditis on follow-up cardiac MRIs based on modified Lake Louise criteria
25
Ferreira VM
Schulz-Menger J
Holmvang G
et al.
Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations.
was uncommon. However, consistent with the few published case series of myocarditis after mRNA COVID-19 vaccination, we observed that nearly half of patients (71/151) with follow-up cardiac MRIs had residual late gadolinium enhancement, suggestive of myocardial scarring.
10
Amir G
Rotstein A
Razon Y
et al.
CMR imaging 6 months after myocarditis associated with the BNT162b2 mRNA COVID-19 vaccine.
,
11
Fronza M
Thavendiranathan P
Karur GR
et al.
Cardiac MRI and clinical follow-up in COVID-19 vaccine-associated myocarditis.
,
12
Jain SS
Steele JM
Fonseca B
et al.
COVID-19 vaccination-associated myocarditis in adolescents.
,
25
Ferreira VM
Schulz-Menger J
Holmvang G
et al.
Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations.
We did not note the degree of late gadolinium enhancement identified during follow-up, but a recent study that assessed serial cardiac MRIs in patients younger than 19 years with myocarditis after COVID-19 vaccination and persistent late gadolinium enhancement showed improvement over time.
30
Hadley SM
Prakash A
Baker AL
et al.
Follow-up cardiac magnetic resonance in children with vaccine-associated myocarditis.
In a small subset of patients, initial cardiac imaging at diagnosis was normal but follow-up imaging was abnormal. It is possible that clinical findings in these patients continued to evolve after diagnosis. Another possibility is that the initial and follow-up imaging results were evaluated by different health-care providers, who had varying interpretations.
In previous studies during the pre-COVID era, cardiac scarring related to myocarditis on follow-up MRI was not uncommon, yet its clinical significance has remained controversial.
10
Amir G
Rotstein A
Razon Y
et al.
CMR imaging 6 months after myocarditis associated with the BNT162b2 mRNA COVID-19 vaccine.
,
31
Grün S
Schumm J
Greulich S
et al.
Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery.
,
32
Law YM
Lal AK
Chen S
et al.
Diagnosis and management of myocarditis in children: a scientific statement from the American Heart Association.
,
33
Dubey S
Agarwal A
Nguyen S
Adebo D
Persistence of late gadolinium enhancement on follow-up CMR imaging in children with acute myocarditis.
Although late gadolinium enhancement during the acute episode of myocarditis has been shown in children and adults to be a possible indication of future adverse cardiac events, including arrythmias, extracorporeal membrane oxygenation, transplantation, and death,
31
Grün S
Schumm J
Greulich S
et al.
Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery.
,
34
Aquaro GD
Perfetti M
Camastra G
et al.
Cardiac Magnetic Resonance Working Group of the Italian Society of Cardiology. Cardiac MR with late gadolinium enhancement in acute myocarditis with preserved systolic function: ITAMY study.
,
35
Lota AS
Tsao A
Owen R
et al.
Prognostic significance of nonischemic myocardial fibrosis in patients with normal LV volumes and ejection-fraction.
,
36
Gräni C
Eichhorn C
Bière L
et al.
Prognostic value of cardiac magnetic resonance tissue characterization in risk stratifying patients with suspected myocarditis.
the importance of late gadolinium enhancement noted on follow-up cardiac MRIs in patients with viral myocarditis is unclear.
31
Grün S
Schumm J
Greulich S
et al.
Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery.
Indeed, guidelines regarding clearance of athletes for competitive sports after myocarditis acknowledge the unclear role of cardiac MRI in the follow-up of such patients.
37
Maron BJ
Udelson JE
Bonow RO
et al.
Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association and American College of Cardiology.
Our follow-up evaluation is subject to several limitations. First, and most importantly, the absence of clear clinical practice guidelines for the outpatient follow-up of myocarditis meant that comparing clinical course among patients was challenging, as no standard level of care was provided. Therefore, some data pertinent to understanding potential residual symptoms and disease were unavailable. We found substantial heterogeneity in the initial evaluation and follow-up of patients, particularly in the cardiac diagnostic imaging received. Current guidelines recommend restricting patients with myocarditis (eg, athletes) from competitive sports for 3–6 months,
38
Bonow RO
Nishimura RA
Thompson PD
Udelson JE
Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 5: valvular heart disease: a scientific statement from the American Heart Association and American College of Cardiology.
although we noted some variability among health-care providers in clearing patients for a return to all physical activity. There are no standard criteria for myocarditis recovery, and we did not identify any clinical feature or diagnostic test results associated with recovery status in the patients we evaluated. Forthcoming expert guidelines regarding the follow-up management and testing of patients with myocarditis could help standardise care in the future.
A second limitation is the passive (or spontaneous) nature of VAERS reporting. Some US cases of myocarditis associated with mRNA COVID-19 vaccination will not have been reported; however, it is unclear how cases reported or not reported initially to VAERS could differ. Selection bias is a possible limitation in any survey activity. Third, although 519 (62%) of the 836 eligible patients with myocarditis who filed a report to VAERS were included in this follow-up evaluation, 275 (33%) declined to participate or were unreachable. Reassuringly, we found no significant differences in the age, sex, race, or census region of respondents compared with non-respondents, although our findings might not be generalisable to all US individuals aged 12–29 years who develop myocarditis after mRNA COVID-19 vaccination due to the small sample size. Fourth, we relied on health-care provider reports for all diagnostic data results. Unlike prospective studies, we did not have access to central interpretation of tests (eg, electrocardiograms, echocardiograms, and cardiac MRIs). Although this limitation probably introduces some variability into the findings, it also reflects real-world practice and data appeared not to be missing at random. A fifth limitation is the absence of a control group for the analysis of patient symptoms. Control groups are important for contextualising symptoms. For example, in a study of long COVID among children and adolescents (aged <21 years) in the USA, Rao and colleagues
39
Rao S
Lee GM
Razzaghi H
et al.
Clinical features and burden of postacute sequelae of SARS-CoV-2 infection in children and adolescents.
found that 41·9% of patients with a history of COVID-19 reported at least one symptom of post-acute sequelae of SARS-CoV-2 infection, as did 38·2% of a control group without a history of COVID-19. Although no pre-myocarditis measures were available for our group of patients with myocarditis, we found that quality of life measures among those with COVID-19 vaccine-associated myocarditis at follow-up were similar to or better than those of contemporary populations studied before or early in the pandemic.
22
Hay JW
Gong CL
Jiao X
et al.
A US population health survey on the impact of COVID-19 using the EQ-5D-5L.
,
23
Jiang R
Janssen MFB
Pickard AS
US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.
Finally, given limitations on the ability to determine causes of myocarditis other than mRNA vaccination, we included all cases in our analyses.
In summary, after at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination, 81% of patients were considered recovered by their health-care provider. At the time of follow-up, these patients reported quality of life measures similar to pre-pandemic reports among individuals of similar ages in the USA. 50% of patients reported at least one symptom at follow-up. Among a subset of 151 patients who had follow-up cardiac MRI results, 54% had an abnormal finding. The CDC is conducting additional follow-up on patients who were not considered recovered at least 12 months since symptom onset, to better understand their longer term outcomes.
MEO, KRB, MJC, MMC, JS, JRS, SSM, JMD, CBC, EBW, DKS, and TTS were responsible for project conceptualisation. IK, JW, PM, and JS were responsible for data curation and data analysis. KRB, MMC, MG, KS, BR, ALV, SSM, AA, AR-C, SN, SSM, DKS, TTS, and SVB provided project administration, supervision, and resources. IK, SVB, MEO, DKS, and TTS wrote the original draft. All authors edited the final version. IK and JW had access to all the data and had final responsibility for the decision to submit for publication.
Over 1,000 reports of adverse events have been lodged with U.S. authorities following COVID-19 vaccination in children aged 5 and younger.
As of Aug. 21, 998 non-serious reports have been entered into the Vaccine Adverse Event Reporting System (VAERS) for children 4 or younger who received a Pfizer vaccine and children 5 or younger who received a Moderna vaccine, Dr. Tom Shimabukuro said on Sept. 1.
Shimabukuro is a researcher with the U.S. Centers for Disease Control and Prevention, which runs VAERS with the U.S. Food and Drug Administration.
Most of the adverse event reports have been for outcomes designated non-serious, or events that did not include death, a life-threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly, or birth defect.
Of the 1,017 total reported events, 19 were designated serious, with 9 for children who received a Moderna vaccine and 10 for children who received a Pfizer vaccine.
Details Omitted
The serious events were not detailed.
“Those details should not have been left out of the information released to ACIP and the public,” Barbara Loe Fisher, co-founder and president of the National Vaccine Information Center, told The Epoch Times in an email.
Shimabukuro was presenting the data (pdf) to the Advisory Committee on Immunization Practices, which advises the CDC on vaccine guidance.
The most commonly reported events after receipt of Pfizer’s vaccine were errors in dosing, such as an incorrect dose being administered. Fever, rash, vomiting, fatigue, and diarrhea were also commonly reported. The most commonly reported events after receipt of Moderna’s vaccine were fever, rash, vomiting, and hives.
The number of reports represented 0.06 percent of the doses administered to children aged 5 or younger, who only became eligible for a vaccine in mid-June.
Shimabukuro said the data from VAERS and other systems did not reveal any new safety concerns.
Anybody can make reports to VAERS, but making a false report subjects a person to a criminal charge. Health care professionals are required to report adverse events for the vaccines under emergency use authorization. Both the Pfizer and Moderna vaccines are under emergency use authorization for young children.
However, research has found that the number of reports submitted to VAERS is an undercount of the actual number of adverse events.
“Even though not every adverse event reported to VAERS is causally related to vaccination, it is also true that one CDC funded study estimated that less than one percent of vaccine adverse events that occur are reported to VAERS,” Fisher said.
Myocarditis
No cases of heart inflammation have been reported following COVID-19 vaccination in the young children.
Myocarditis and pericarditis, forms of heart inflammation, were also not detected in the original clinical trials. Studies have since conclusively linked them to the Moderna and Pfizer vaccines.
The reported rates of myocarditis after dose 2 of a primary series are elevated for males aged 5 to 49 and for females aged 12 to 29. The highest reported rate is 78.7 per million second doses administered, for males between 16 and 17 years old.
The reported rates remain elevated for males 12 to 29 after a booster dose, Shimabukuro said. The rates do not remain elevated for females of any age after a booster dose, according to the VAERS data.
The CDC has verified 131 of the myocarditis case reports among people aged 5 and up after booster shots.
Data from another surveillance system run by the CDC, the Vaccine Safety Datalink, showed a safety signal for a first booster for myocarditis and pericarditis after a first booster. The Pfizer vaccine caused 61.7 excess heart inflammation events for males aged 12 to 15 and 189 excess events for males aged 16 and 17. The vaccines caused 30.9 excess events for males aged 18 to 39.
The rates were higher for both males and females aged 16 and 17 after a booster of Pfizer’s shot, though the higher rates were not statistically significant because of the low number of events, Shimabukuro said.
A well-designed observational study of the entire French population, just published on June 25 in Nature, has again definitively confirmed (here; here; here; here) observations first noted during February, 2021: covid-19 mRNA vaccination confers an excess risk for serious inflammation (here; here) of the heart—both its muscle (“myocarditis”), and suspending covering (“pericarditis”)—particularly in men under 30 years of age.
Two weeks earlier, June 9, Rhode Island Hospital investigators published the (magnetic resonance) imaging findings from 14 cases of young Rhode Island men (median age 19; mean age 21 ± 6 years old), hospitalized for myopericarditis after covid-19 mRNA vaccination, between January and September, 2021, in the journal Radiology: Cardiothoracic Imaging.
I received an email from the report’s first author confirming that typical of these presentations, all 14 of the young men were free of comorbidity. The anonymous individual whose plight is the focus of this Brown University exposé was almost certainly included amongst those cases.
The following information was volunteered to me, as an unsolicited confessional, during a recent tangential conversation with a Rhode Island caregiver:
(Informant): “It (coverage of the inpatient service) was very sporadic, at The um Miriam (Hospital), and even in that short exposure I saw three cases, or knew of at least three cases, of probable (covid-19) vaccine-related myocarditis”…
(Informant): “There was another kid, a Brown University student who was volunteering at the (Miriam) Hospital”…
(Dr. Bostom): “And he got vaccinated to do that, right?”
(Informant): “He got vaccinated, and shortly after had a very high troponin (blood test marker of heart muscle injury). It was an old scale troponin. It was like 45, and that would be 4,500…”
(Dr. Bostom): “4,500, exactly, yeah.”
(Informant): “What’s that?”
(Dr. Bostom): “Yeah 4.500. That’s what they’re reporting; that’s what they’re reporting now (i.e., for post-covid-19 vaccine-induced myocarditis troponin elevations).”
(Informant): “His was high.”
(Dr. Bostom): “Did he have to be hospitalized at least for monitoring?”
(Informant): “He got hospitalized my last night on call. I remember his parents were extremely concerned. I had administrators calling me from down south where his parents lived.”
(Dr. Bostom): “This was a Brown student?”
(Informant): “Yeah a Brown student.”
My informant, in an email after our conversation, further claimed their coverage of the Miriam Hospital inpatient service “was around March, 2021.” None of the data the informant provided, it must be emphasized, disclosed any of the 18 “information identifiers,” that when conjoined to health information, “become PHI (personal health information).”
Two deidentified public datasets, which I had been studying for months before my conversation with the informant, provided strong, independent evidence corroborating my informant’s claims.
The Centers For Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS) contains a case report of a 20-year-old hospitalized in Rhode Island during March, 2021 for post-Pfizer Covid-19 mRNA vaccine-induced myopericarditis. The VAERS report records a 20-year-old male initially vaccinated with Pfizer’s Covid-19 mRNA vaccine on 2/26/21, received his second dose 3/18/21, developed chest pain on 3/20/21, and was hospitalized through the Emergency Department beginning on 3/22/21, for 3 days.
Electrocardiogram, imaging studies, and troponin elevation (a marker of heart muscle injury), were all consistent with acute myopericarditis. He was SARS-CoV-2 negative on PCR (polymerase chain reaction) testing, and also SARS-CoV-2 nucleocapsid antibody negative, both consistent with no current or recent SARS-CoV-2 infection.
The rest of his work-up for other viral etiologies of myopericarditis was negative. (A link to the full VAERS pdf report for VAERS ID 1347752-1 can be downloaded here. Corroborative data from a deidentified Rhode Island Department of Health 2021 discharge dataset on all hospitalizations in the state revealed that a 20-year-old white male from Florida (“down south,” per informant), with no baseline comorbidity other than mild asthma, was hospitalized at The Miriam Hospital with a primary diagnosis of (myo)pericarditis during March, 2021 for a 3-day length of stay. He apparently experienced a serious heart rhythm disturbance, ventricular tachycardia, during his hospitalization.
Additional indirect public evidence confirms the unique early timing of the Brown student’s vaccination, and vaccine injury. Rhode Island did not make covid-19 vaccines available to the general public for 16+ year-olds until 4/19/21, with only a “limited supply.”
Brown’s first campus covid-19 vaccine clinic/drive was on May 17, 2021. According to the VAERS report, the ostensible Brown student, a 20-year old-male, got his first vaccine dose on Feb. 26, 2021—almost 2-months before the vaccine became widely available in his age group in Rhode Island. This timing is consistent with the informant’s statement, “a Brown University student [who] was volunteering at the (Miriam) Hospital,” entitling the student to receive the vaccine before it was generally accessible to persons his age.
Brown University, through its Department of Public Safety, routinely transmits anonymized safety alerts to the student community regarding such banalities as minor assault, robbery, hate crime, arson, and even suspicious packages. There is no evidence, in contrast, that the University ever issued a comparable anonymized “health safety alert”—notably to its vulnerable healthy 18 to 24 year-old male population—about the March, 2021 case of fulminant, post-covid-19 vaccine myopericarditis experienced by a healthy 20-year-old male Brown student.
Absent any apparent campus discussion of this serious, and potentially lethal (here; here; here; here) vaccine injury, Brown University, some 2 months later, in mid-May, 2021, launched an aggressive, mandatory covid-19 vaccination campaign. Russell Carey, a Brown Planning and Policy administrator, crowed about the University having vaccinated “77.2%” of its students already by the first week of July, 2021.
Moreover, 15 months after the March, 2021 student vaccine injury, Brown’s Carey, its de facto covid-19 rule enforcement “czar,” and Brown University President, Dr. Christina Paxson, still refused to acknowledge the episode, let alone comment on its obvious risk/benefit-based ramifications for the University’s mandatory covid-19 vaccination policy.
During June, 2022, Mr. Carey, and President Paxson, were emailed descriptive information, and accompanying queries, about the student vaccine injury case. I corresponded with Mr. Carey. A friend and concerned parent of a Brown student (the parent is also a Brown University alumnus), wrote to Dr. Paxson.
My emails to Mr. Carey summarized the key corroborative evidence detailed previously about the Brown student covid vaccine-injury myopericarditis case. I then simply asked Mr. Carey to acknowledge that indeed the Brown student had been hospitalized for myopericarditis in March, 2021, shortly after his second mRNA covid-19 vaccine dose. I posed these additional questions:
“From the beginning of the covid-19 pandemic in February/March 2020, through the time of this student’s putative hospitalization, in March, 2021, how many Brown undergraduate students were hospitalized, if any, for a confirmed covid-19 pneumonia/lower respiratory tract infection?
At any time since the covid-19 vaccine mandate was first announced at Brown in April, 2021, through its broad implementation starting the summer/fall of 2021, and the April, 2022 announcement the mandate would extend to the incoming class of 2022-23, were Brown undergraduates, or incoming 2022-23 freshman, ever apprised about the March, 2021 vaccine-induced myocarditis case, juxtaposed to the number of undergraduate students (again, if any) hospitalized for covid-19 pneumonia/lower respiratory tract infection, as part of an appropriate risk/benefit-based discussion of informed consent?”
Mr. Carey declined to reply. The emails can be viewed in their entirety here. I would add for context that the State University of New York (SUNY) covid-19 dashboard transparently displays their aggregated covid-19-related hospitalization data since the beginning of the pandemic. That tally for SUNY’s ~326,000 undergraduate students is zero. Brown’s total population of undergraduates is ~6800.
The parent’s email to Dr. Paxson covered much of the same evidentiary ground as my letter to Mr. Carey, in even greater detail. It also included plaintive, direct personal appeals to Dr. Paxson’s reason and ethos. To protect the parent’s privacy, and her desired relationship with Dr. Paxson, I have not shared the parent’s email, or Dr. Paxson’s response. Dr. Paxson’s response was extremely succinct, non-sequitur, and indifferent.
When Brown University’s Dean of the School of Public Health, Dr. Ashish Jha, was appointed Biden White House “coronavirus response coordinator,” on March 17, 2022, Dr. Paxson gushed that his appointment
“brings a top scholar and highly regarded Brown academic leader to White House service… Ashish will bring to President Biden and our nation what he has brought — and will bring back [note: his assignment is temporary] — to Brown: an unrivaled commitment to improving public health…with heart and a commitment to science.”
Three months afterwards, Brown University’s, and Dr. Paxson’s much ballyhooed Dr. Jha offered up a public example of blatant anti-scientific propaganda. During a national CBS News television interview from the White House lawn on June 20, 2022, referring to covid-19 vaccination across the entire age spectrum, Jha made the blanket counterfactual claim, “Thankfully, there have not been any serious side effects of these vaccines.”
The Rhode Island Department of Health (RIDOH) demonstrated its own lack of interest in either recording covid-19 vaccine-injured myopericarditis cases, or monitoring the longer-term recovery of those individuals. In an email exchange with RIDOH’s spokesman, I pointed to the recently published report of 14 RI cases of myopericarditis in young men, and the May, 2021 newspaper account of how Connecticut’s Department of Health had already, over a year ago, tabulated 18 such cases in 16 to 34-year-old men, while, the “number and severity of cases is being tracked…by the state of Connecticut to gain more information.”
The brief, disinterested response to my queries about whether RIDOH had “1) issued any similar statements, in 2021 or 2022, & 2) is RIDOH in fact compiling and tracking such cases?”, was, “As you know, CDC, FDA (Food and Drug Administration), and HHS (Health and Human Services) maintain a reporting and tracking system for vaccine adverse events. The State (RI) does not maintain a separate system. We have not issued any statements on myopericarditis post-COVID-19 vaccination.”
Only limited gold-standard, evidence-based data (here; here) on covid-19 mRNA vaccine risk/benefit (for all ages, combined) are available from randomized, placebo-controlled clinical trials. These data reveal no total, or covid-19- mortality benefit. More ominously, they suggest specific vaccine-injury serious adverse events, “surpassed the risk reduction for covid-19 hospitalization relative to the placebo group, in both the Pfizer and Moderna trials.” It is well-nigh axiomatic that the latter unfavorable risk/benefit calculations would be worse in populations with near zero risk for hospitalization due to covid-19, including healthy college students.
A 1977 California Law Review essay noted that informed consent case law, “emphasizes the right of the individual to be informed about proposed medical procedures, thus promoting the intelligent exercise of personal autonomy.” Despite recognizing some personal autonomy limitations when vaccinations are requisite for school attendance, the essay further argued, “[B]ecause the risks and benefits of immunization are often closely balanced, the risks of vaccination will often be material and should be disclosed. Moreover, the rationale of the modern informed consent cases justifies disclosure of risks and benefitseven where the vaccination is required for school entry.” The essay concluded with this admonition: “The patient must be allowed to make the decision and therefore should not simply be reassured that the vaccine’s risks are outweighed by its benefits.”
Over four decades later, in their zealously shared promotion and enforcement of indiscriminate covid-19 vaccine mandates, both Brown University and the Rhode Island Department of Health have chosen explicitly (see this informed consent template) to ignore these established legal, ethical, and scientific guidelines.
Summary/Conclusion
In March, 2021, two months before enacting its mandatory, aggressive covid-19 vaccination campaign, a healthy 20-year-old male Brown University student was apparently hospitalized for covid-19 vaccine-induced myopericarditis. The University never disclosed this hospitalization, then, till now, ignoring the established ethics of risk/benefit-based informed consent.
Brown University, in tandem with the Rhode Island Department of Health, forms a powerful duopoly of denial controlling state policy, and “acceptable” discourse on covid-19 vaccine injury. Frank, open discussion of the Brown student vaccine-injury myopericarditis case, and the larger issue of serious covid-19 vaccine-injury, especially among the vast swath of young, healthy Rhode Islanders, invulnerable to severe covid illness, is verboten. The baleful Brown-RIDOH duopoly enforces that silence.
Andrew Bostom, M.D. MS, is an academic clinical trialist and epidemiologist, who is currently a Research Physician at the Brown University Center For Primary Care and Prevention of Kent-Memorial Hospital in Rhode Island.
Between May 12, 2021 and October 31, 2021, within a population of 32 million persons aged 12 to 50 years, 21.2 million first (19.3 million second) doses of the BNT162b2 vaccine and 2.86 million first (2.58 million second) doses of the mRNA-1273 vaccine were received (Table S1). In the same period, 1612 cases of myocarditis (of which 87 [5.4%] had also a pericarditis as associated diagnosis) and 1613 cases of pericarditis (37 [2.3%] with myocarditis as associated diagnosis) were recorded in France. We matched those cases to 16,120 and 16,130 control subjects, respectively. The characteristics of the cases and their matched controls are shown in Table 1. For both myocarditis and pericarditis, key differences between cases and controls included a higher proportion among cases of a history of myocarditis or pericarditis, of history of SARS-CoV-2 infection, and receipt of an mRNA Covid-19 vaccine. The mean age and proportion of women were lower among patients with myocarditis than those with pericarditis.
Table 1 Characteristics of study cases and controls.
Risk of myocarditis and pericarditis associated with vaccination
For both vaccines, the risk of myocarditis was increased in the seven days post vaccination (Table 2; in the rest of the text, we will refer to multivariable odds ratios). For the BNT162b2 vaccine, odds ratios were 1.8 (95% confidence interval [CI]: 1.3–2.5) for the first dose and 8.1 (95% CI, 6.7–9.9) for the second. The association was stronger for the mRNA-1273 vaccine with odds-ratios of 3.0 (95% CI, 1.4–6.2) for the first dose and 30 (95% CI, 21–43) for the second. The risk of pericarditis was increased in the seven days following the second dose of both vaccines, with odds ratios of 2.9 (95% CI, 2.3–3.8) for the BNT162b2 vaccine and 5.5 (95% CI, 3.3–9.0) for the mRNA-1273 vaccine. Vaccination in the previous 8 to 21 days, with either the BNT162b2 or mRNA-1273 vaccine was not associated with a risk of myocarditis or pericarditis. Independently of vaccination status, a history of myocarditis was strongly associated with a risk of contracting myocarditis during the study period, with an odds-ratios of 160 (95% CI, 83–330). The same was true for pericarditis, with an odds ratio of 250 (95% CI, 120–540). No interaction was found between history of myocarditis or pericarditis and vaccine exposure. Infection with SARS-CoV-2 in the preceding month was also associated with a risk of myocarditis (odds ratio, 9.0 [95% CI, 6.4–13]) or pericarditis (odds ratio, 4.0 [95% CI, 2.7–5.9]).
Table 2 Association between myocarditis and pericarditis and exposure to mRNA vaccines within 1 to 7 days and 8 to 21 days.
Subgroup estimates by sex and age classes
The risk of myocarditis was substantially increased within the first week post vaccination in both males and females (Fig. 1 and Table S2). Odds-ratios associated with the second dose of the mRNA-1273 vaccine were consistently the highest, with values up to 44 (95% CI, 22–88) and 41 (95% CI, 12–140), respectively in males and females aged 18 to 24 years but remaining high in older age groups. Odds-ratios for the second dose of the BNT162b2 vaccine tended to decrease with age, from 18 (95% CI, 9–35) and 7.1 (95% CI, 1.5–33), respectively in males and females aged 12 to 17 years, down to 3.0 (95% CI, 1.5–5.9) and 1.9 (95% CI, 0.39–9.3), respectively in males and females aged 40 to 51 years.
Fig. 1: Association between myocarditis and exposure to mRNA vaccines within 7 days, according to sex and age group.
Adjusted odds-ratio (aOR) from multivariable model are represented in base 10 logarithmic scale according to age groups (x-axis), by sex (columns) and vaccine dose ranking (rows). Colors denote the type of vaccine. Centre value are aOR point estimates and error bars represent 95% confidence intervals. Number of cases (N) by age categories (12–17, 18–24, 25–29, 30–39, 40–50 and 12–50 years) are respectively as follows: N = 137, 480, 210, 273, 181 and 1281 for males, and N = 29, 106, 40, 88, 68 and 331 for females. aOR could not be calculated in categories where no case exposed to vaccine was recorded, for instance for males and females aged 12 to 17 years having received the mRNA-1273 vaccine.
An increased risk of pericarditis was also found in the first week after the second dose of either of the mRNA vaccines among both males and females (Fig. 2 and Table S3). Odds-ratios for the second dose of the BNT162b2 vaccine showed a downward trend across age groups with values up to 6.8 (95% CI, 2.3–20) and 10 (95% CI, 2.5–41), respectively in males and females aged 12 to 17 years. The second dose of the mRNA-1273 vaccine was associated with pericarditis among males and among females only within age 30 to 39 years (odds-ratio 20 [95% CI, 3.5–110]) and age 40 to 50 years (odds-ratio 13 [95% CI, 3.5–49]).
Fig. 2: Association between pericarditis and exposure to mRNA vaccines within 7 days, according to sex and age group.
Adjusted odds-ratio (aOR) from multivariable model are represented in base 10 logarithmic scale according to age groups (x-axis), by sex (columns) and vaccine dose ranking (rows). Colors denote the type of vaccine. Centre value are aOR point estimates and error bars represent 95% confidence intervals. Number of cases (N) by age categories (12–17, 18–24, 25–29, 30–39, 40–50 and 12–50 years) are respectively as follows: N = 65, 194, 106, 282, 342 and 989 for males, and N = 36, 118, 91, 183, 196 and 624 for females. aOR could not be calculated in categories where no case exposed to vaccine was recorded, for instance for males and females aged 12 to 17 years having received the mRNA-1273 vaccine.
Associations between vaccination within the seven preceding days and the risk of myocarditis or pericarditis were of the same magnitude when the analysis was restricted to the period prior to the warning against myocarditis and pericarditis as adverse events sent to prescribers on July 19, 2021 (Fig. S1 and Table S4). The results were unchanged in models excluding patients with a history of SARS-CoV-2 infection in the past month, those with a history of myocarditis or pericarditis within five years, those diagnosed with both myocarditis and pericarditis, or those with a hospitalization within a month prior to index date.
Excess events
We estimated the number of excess cases attributable to vaccines by sex and age group (Fig. 3). The number of excess cases of myocarditis per 100,000 doses administered to adolescent males 12 to 17 years was 1.9 (95% CI, 1.4–2.6) for the second dose of the BNT162b2 vaccine and for young adults 18 to 24 years of age reached 4.7 (95% CI, 3.8–5.8) for the second dose of the BNT162b2 vaccine, and 17 (95% CI, 13–23) for the second dose of the mRNA-1273 vaccine (Fig. 3). This translates into one case of vaccine-associated myocarditis per 52,300 (95% CI, 38,200–74,100) second doses of the BNT162b2 vaccine among 12–17 years, and 21,100 (95% CI, 17,400–26,000) second doses of the BNT162b2 vaccine and 5900 (95% CI, 4400–8000) second doses of the mRNA-1273 vaccine among 18–24 years (Table S5). Estimates of excess cases were lower for older age groups and generally for females. However, the number of excess cases of myocarditis attributable to the second dose of the mRNA-1273 vaccine was consistently higher. Among females aged 18 to 24 years, the estimated number of excess cases of myocarditis per 100,000 doses reached 0.63 (95% CI, 0.34–1.1) for the second dose of the BNT162b2 vaccine (corresponding to 1 case per 159,000 [95% CI, 90,800–294,400] doses) and 5.3 (95% CI, 3.0–9.1) for the second dose of the mRNA-1273 vaccine (corresponding to 1 case per 18,700 [95% CI, 11,000–33,400] doses). The number of excess cases of pericarditis is presented in Fig. 3. As for myocarditis, estimates for the second dose of the mRNA-1273 vaccine were consistently higher.
Fig. 3: Excess cases of myocarditis and pericarditis attributable to mRNA vaccines according to sex and age group, per 100,000 doses.
Excess cases are based on the risk in the 7 days following vaccination. Colors denote the type of vaccine and the shape of point estimate denotes the ranking of dose vaccine. Centre value are excess cases point estimates and error bars represent 95% confidence intervals. Number of cases (N) by age categories (12–17, 18–24, 25–29, 30–39, 40–50 and 12–50 years) are respectively as follows: for cases of myocarditis, N = 137, 480, 210, 273, 181 and 1281 in males, and N = 29, 106, 40, 88, 68 and 331 in females; for cases of pericarditis, N = 65, 194, 106, 282, 342 and 989 in males, and N = 36, 118, 91, 183, 196 and 624 in females. Excess cases was only calculated in categories with a significantly positive association between the vaccine exposure and the outcome (adjusted odds-ratio >1).
Characteristics of myocarditis and pericarditis cases occurring after vaccination
Among exposed cases, the delay between administration of the vaccine and hospitalization (Fig. S2) was shorter after the second dose than after the first dose, both for myocarditis (median of 4 days versus 10 days after the BNT162b2 vaccine and of 3.5 days versus 9 days after the mRNA-1273 vaccine) and for pericarditis (median of 6 days versus 10 days after the BNT162b2 vaccine and of 3 days versus 11 days after the mRNA-1273 vaccine).
Table 3 shows the characteristics of cases acquired within 7 days of vaccination (deemed post-vaccination cases) compared to those acquired within a larger delay or in the absence of vaccination. Post-vaccination cases were significantly younger (predominantly in 18 to 24 years), more frequently concerned males for myocarditis but not for pericarditis, and without a history of myocarditis or pericarditis, respectively, or of SARS-CoV-2 infection. The lengths of hospital stay were not significantly different in post-vaccination cases of myocarditis (median 4 days) and pericarditis (median 2 days) than in unexposed cases. The frequency of admission in intensive care unit, mechanical ventilation or death was lower for post-vaccination cases than for unexposed cases. After a follow-up of 30 days after discharge, 4 (0.24%) deaths among cases of myocarditis (none among exposed to vaccine) and 5 (0.31%) deaths among cases of pericarditis (including one patient having received a vaccine 8 to 21 days prior to the diagnosis) were reported. Of those, 3 and 2 died during their hospital stay for myocarditis and pericarditis, respectively.
Table 3 Description of hospitalized patients according to the exposure to mRNA vaccines.
Drugs treatments within 30 days after hospital discharge are presented in Figs. S3 and S4. Regardless of the vaccination status, the therapeutic classes most frequently used during the follow-up of myocarditis cases included beta blocking agents (63% of patients), analgesics (52%) and agents acting on the renin−angiotensin system (46%). The corresponding treatments of pericarditis cases were analgesics (83%), colchicine (69%) and beta blocking agents (14%) (Fig. S4).
A healthcare worker prepares a dose of the Pfizer-BioNTech Covid-19 vaccine at a vaccination clinic in the Peabody Institute Library in Peabody, Massachusetts, on Wednesday, Jan. 26, 2022.
Vanessa Leroy | Bloomberg | Getty Images
The U.S. Centers for Disease Control and Prevention said this week that younger males should consider waiting longer between doses of Pfizer’s and Moderna’s vaccines to reduce a rare risk of heart inflammation.
The CDC said males ages 12- to 39-years-old should consider waiting eight weeks between the first and second doses of their primary Covid vaccination series. Public health authorities in Canada found the risk of myocarditis in men ages 18- to 24-years-old was lower when they waited eight weeks for the second dose of Moderna or Pfizer.
The CDC recommends that other eligible individuals wait three weeks between Pfizer shots and four weeks between Moderna doses, particularly the elderly and those with compromised immune systems.
Myocarditis is an inflammation of the heart muscle than can result in serious health problems, according to the National Heart, Lung and Blood Institute. Myocarditis most commonly occurs after viral infections, but the CDC has also found a link with between Moderna’s and Pfizer’s shots and myocarditis, particularly after the second dose.
The risk of myocarditis among men ages 18 to 39 is about 1.5 times higher after a second Moderna dose than with Pfizer’s vaccine. Men in this age group report about 68 myocarditis cases per 1 million Moderna second doses administered, compared with 47 myocarditis cases per 1 million Pfizer second doses administered.
Most patients who develop myocarditis after Covid vaccination respond well to medicine and recover fully, according the CDC. People face a much higher risk of developing myocarditis after Covid infection than from the vaccines, according to the Department of Health and Human Services.
Two of the nation’s top doctors said they refuse to give their own kids a third COVID shot as vaccinated teenage boys have a low risk of hospitalization, but the likelihood of myocarditis, an inflammation of the heart, caused by the jab is 10 out of 100,000.
Dr. Monica Gandhi, an infectious-disease specialist at the University of California, and Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA’s vaccine advisory committee, told journalist David Zweig in a piece published on Bari Weiss’s Substack, Common Sense, that the benefits of a booster for teen males are outweighed by the possible side effects.
One of the most common serious side effects for a teen from a COVID booster jab was myocarditis, a rare heart inflammation case that occurs in males at almost nine-times the rate than females, according to the Centers for Disease Control and Prevention (CDC), which had recorded two such cases among a group of 20,000 while COVID-vaccinated teen boys only had a 0.3 out of 100,000 chances of being hospitalized over COVID, according to the agency’s COVID briefings and Advisory Committee on Immunization Practices report in early January.
The doctors, who have both advocated for the vaccine and gotten themselves and their children immunized, claimed the CDC was premature in advising teens to get a COVID booster shot on January 5, with Gandhi saying, ‘I am not giving my 12 and 14-year-old boys boosters.’
Offit said he advised his 20-year-old son to avoid the third dose and said the booster would be worth the risk for ‘the average healthy 17-year-old boy.’
The doctors’ statements come as other health officials claimed the CDC had made its booster recommendation without proper data on the safety issues.
The US and Germany are one of the few countries that have recommended booster shots for everyone 12 and up, with the UK and Finland only recommending it for teens with serious medical conditions.
Denmark, Sweden, Japan and Spain have approved boosters for adults only, and in Ireland, no one under the age of 16 can receive a booster.
Dr. Monica Gandhi, an infectious-disease specialist at the University of California, and Dr. Paul Offit, a member of the FDA’s vaccine advisory committee, said the benefits of a booster shot for teen boys was outweighed by its possible side effects
The CDC reported two cases of myocarditis due to booster shots in teen boys. Both men were released from the hospital and reported in good condition
Of the 265 cases reported in teens ages 12 to 15 last year, 251 were hospitalized and all but 10 were discharged and sent home. The remaining have reported improved or resolved symptoms, but were still under evaluation
Myocarditis was listed as the second most common serious side effect due to vaccination among older teens and young men. There were only 13 cases reported in the age group between May to December 2021, with the four hospitalized reportedly recovered
CDC’S ADVISORY OF MYOCARDITIS AFTER A VACCINE SHOT
Cases of myocarditis reported to the Vaccine Adverse Event Reporting System have occurred:
After mRNA COVID-19 vaccination (Pfizer-BioNTech or Moderna), especially in male adolescents and young adults
More often after the second dose
Usually within a week of vaccination
Most patients with myocarditis who received care responded well to medicine and rest and felt better quickly.
Patients can usually return to their normal daily activities after their symptoms improve. Those who have been diagnosed with myocarditis should consult with their cardiologist (heart doctor) about return to exercise or sports. More information will be shared as it becomes available.
Myocarditis has the following symptoms:
Chest pain
Shortness of breath
Feelings of having a fast-beating, fluttering, or pounding heart
Seek medical care if you or your child have any of the specific or general symptoms of myocarditis, especially if it’s within a week after COVID-19 vaccination.
The CDC had recorded 265 cases of myocarditis among children ages 12 to 15 who received a COVID vaccine between May 12 and December 19, 2021, 90 percent of which were boys, according to the CDC’s Advisory Committee on Immunization Practices in their January 5 report.
Of the cases, 251 were hospitalized and all but 10 were discharged and sent home. The remaining have reported improved or resolved symptoms, but were still under evaluation.
Within that same timeframe, the CDC recorded 13 cases of myocarditis among people ages 16 to 24, with four being hospitalized and all four recovering.
During a United Nations briefing last week, WHO Chief Scientist Dr. Soumya Swaminathan said: ‘There is no evidence that healthy children or healthy adolescents need boosters. No evidence at all.’
The sentiments were echoed by Dr. Sarah Long, a member of the CDC advisory committee and a infectious disease specialist at Drexel University.
‘We made the decision, in my opinion, without any data on safety,’ she said, referencing the CDC’s decision to ignore a study from Israel that cited two cases of myocarditis in 12 to 15-year-old males because of its small survey size.
The Israeli study warned that the condition could be as high as one in 3,000 males following vaccination.
It echoed the research done in China and Ontario, with the Chinese study concluding that teen boys had a 37 out of 100,000 chance of developing acute myocarditis after their second vaccine dose.
In Ontario, Public Health officials officials reported 636 cases of myocarditis after the distribution of more than 29 million doses from December 2020 to January 2022.
Public Health Ontario concluded that there was there was a 34.8 out of 100,000 chance of a teen boy to experience adverse effects following their second COVID jab.
When the CDC and FDA created committees to research the impact of the booster shots in September 2021, the committees voted against sweeping proposals for the third shots, instead approving the boosters for limited groups.
The CDC’s vote was overruled by its director, Dr. Rochelle Walensky on September 24 as the agency recommended the boosters for not just seniors, but for 18 and up.
On January 5, the agency then voted to recommend the boosters to those 12 to 17 years old.
Despite some concerns over the studies on the boosters impact on young adults, Long said she ultimately voted to approve the boosters for teens due to the rampant surge of the Omicron variant.
The only member on the advisory committee who voted against the booster recommendation was Dr. Helen Keipp Talbot, an infectious disease specialist at Vanderbilt.
Talbot did not immediately respond to DailyMail.com’s request for comment.
Offit, who has been vocal about the problems with the government’s recommendations for the boosters, told New York Magazine in December that while the boosters were important, they do not yield much benefit to younger people.
‘I’m not opposed to booster dosing. What I think we need to make clearer is why we’re boosting,’ he said.
‘There is certainly a value to boosting people who are older or people who live in long-term-care facilities. The question is, if we’re saying that healthy, young people need a booster dose, which is what we’ve just said, I think we need to explain to the American public that we’re getting prevention, for the most part, against mild illness, and it might not be long-lived.
‘On the one hand you have the CDC recommending a booster dose for everybody over 18, which was rejected twice by the FDA’s vaccine advisory committee and the CDC’s advisory committee, and then on the other hand you have research institutes, universities, colleges, and hospitals that now have three-dose mandates while others have two-dose mandates. We’ve confused people.’
Gandhi told the Atlantic in October that booster recommendation debate was a debacle
‘The entire booster discussion played out in the public eye,’ she said. ‘It played out that we weren’t a ‘together’ country in terms of our health recommendations.’
Dr. Elissa Perkins, an emergency medicine physician at Boston University with an expertise in infectious diseases, told Zweig that the CDC and FDA needed to communicate the recommendation decision better to put parents at ease.
‘If a booster is only offering a temporary benefit against minimally symptomatic infection it is really important that this rationale is clear so parents can weigh the trade offs to determine if, in their individual circumstances, the benefits outweigh the risks,’ she said.
The backlash against the booster recommendation for kids comes as schools grapple with what policies to enforce as COVID cases remain high.
The US recorded 653,120 new cases in the past day and about 4,040 new deaths, according to Johns Hopkins University.
Two weeks ago marked the nation’s highest weekly infection rate of the pandemic, with 5,607,176 cases reported between January 10 to 16. It was also the deadliest week with 23,416 deaths reported.
About 64 percent of eligible Americans are fully vaccinated, more than 80 percent have gotten at least one jab.
