BY ANISH KOKA

A national study from Korea published in the European Heart Journal sheds important new light on complications related to COVID vaccine related myocarditis. While US public health authorities have been convinced from the very beginning about how safe and effective the new vaccines are, researchers in other countries with far smaller budgets have been testing that theory.

It was Israeli researchers that first highlighted the novel mRNA vaccines as potentially causing myocarditis in the Spring of 2021, but it has proven difficult to quantify the risk of severe complications beyond scattered case reports of severe morbidity and mortality. In part, US researchers are hampered by vaccine reporting systems in the US that are passive surveillance systems relying on voluntary reporting of vaccine adverse events. This has the potential of under-reporting adverse events, which was exactly the conclusion of an earlier JAMA analysis on US VAERS vaccine myocarditis cases.

Diving deep into the methods and results of the study

The South Korean approach was to organize a national reporting system under the auspices of the Korean Disease Control and Prevention Agency (KDCA). The KDCA also established a reporting system with a legal obligation for special adverse events including myocarditis and pericarditis after COVID-19 vaccination. To evaluate all reported cases of suspected myocarditis or pericarditis after COVID-19 vaccination, the KDCA organized an “Expert Adjudication Committee on COVID-19 Vaccination Pericarditis/Myocarditis”. The committee comprised 7 experts in cardiology, 1 in infectious disease, 2 in epidemiology, epidemiologic investigators in 16 regional centers, and officials from the KDCA.

Among 44,276,704 subjects vaccinated from 26 February to 31 December 2021, 1533 cases of suspected myocarditis were reported to the KDCA. The committee adopted the myocarditis case definition and classification of the Brighton Collaboration (BC) (see figure below) for the diagnosis and degree of certainty of a Vaccine Related Myocarditis (VRM) diagnosis.

Acute myocarditis that developed within 42 days after COVID-19 vaccination was considered a COVID-19 VRM. To minimize the risk of an inaccurate diagnosis, the committee rejected the level 3 BC case definition of myocarditis and the level 2 BC case definition that did not have associated cardiac damage evident on a blood test or any case with a positive result for COVID-19 infection. In the few cases where cardiac markers were not performed or were not in an abnormal range, confirmatory testing with endocardial biopsy or cardiac MRI confirmed the diagnosis of VRM.

The adjudication committee also examined other potential causes of myocarditis, such as the presence of antibodies against various viruses and autoimmune markers in their review of the medical records.

A review of the South Korean vaccination record shows 86% of the population was vaccinated in the 10 months the study examined (Feb 2021 – Dec 2021). The vaccine most commonly used was the Pfizer BNT162b2 mrna vaccine (56%), followed by the AstraZeneca adenoviral vector vaccine ChadOx1 (25%), and the moderna mrna-1273 vaccine (15%).

Of the 1533 cases of potential vaccine myocarditis reported, the expert adjudication committee confirmed 480 Covid 19 VRM cases. The incidence of VRM was highest in 12-17 year old males with a rate of 5.29 /100,000 persons.

Severe COVID-19 VRM was identified in 95 cases (19.8%), 85 ICU admissions (17.7%), 36 Fulminant Myocarditis cases (7.5%), 21 ECMO therapies (4.4%) ( a modified heart lung bypass), 21 deaths (4.4%), and 1 heart transplantation (0.2%).

Autopsy studies were done for all sudden death cases after COVID-19 vaccination in Korea because of a national compensation program for vaccine injuries. This identified eight cases of sudden cardiac death as caused by VRM that were not known until the autopsy was performed. All sudden cardiac death developed within a week after mRNA vaccination and occurred in individuals under the age of 45.

What we learn from this study

The South Koreans would appear to have hit on how to minimize both under and over-reporting of vaccine adverse events by combining a legal obligation to report that makes underreporting less likely, and assembling an expert committee to review individual case reports to adjudicate cause appropriately. Extrapolating their results to other vaccinated populations still needs to be done carefully because vaccine adverse events may differ by race/ethnicity , as well as type of vaccine that was primarily deployed in a population. The Moderna mrna-1273 vaccine has 3x the dose as the Pfizer BNT162b2 mrna vaccine and has been widely reported to have higher rates of vaccine myocarditis. The South Korean population was mostly vaccinated with the Pfizer mRNA vaccine and the AstraZeneca adenoviral vector vaccine (rarely associated with VRM).

The highest risk group, as has been repeatedly shown elsewhere, was 12-17 year old boys with a rate of 5.2/100,000 boys. This rate, in the United States, would conservatively translate to ~650 boys (~160 girls) with vaccine related myocarditis if the entire population of 12-17 year olds was vaccinated. The US did have a lot more moderna vaccine available which means the rate of VRM would likely have been higher (37% of vaccines given in the US were moderna vaccines per the CDC) here than in South Korea.

These are all approximate numbers , of course, and a variety of factors could move these estimates up or down. We don’t have details of the ~1100 potential cases of VRM that were thrown out by the expert committee, vaccination rates vary widely in different populations, the type of vaccine available with differing rates of VRM, and certain adverse events may differ based on race/ethnicity.

But these rates are in line with a few other large datasets which lends credibility to the estimates. There are some results here that are surprising and concerning. It is little secret by this point that US public health authorities have been so committed to the vaccines being safe and effective to support their universal vaccination campaign that their first response to reports of vaccine myocarditis was to first deny, and once that ship sailed, to emphasize the ‘mildness’ of vaccine myocarditis.

The incomplete datasets available to date have largely characterized VRM as a self limited illness that requires a precautionary hospital stay for 24 hours that can be treated with Motrin. While there have been case reports published of severe VRM, Israeli and US data found no severe cases in their published series. The South Korean data, in stark contrast to the ‘mild and favorable prognosis’ narrative found 20% of VRM cases were severe.

– Severe VRM was identified in 95 cases (19.8% of total VRM)

– 85 intensive care unit admission (17.7%)

– 21 extracorporeal membrane oxygenation therapy (4.4%)

– 21 deaths (4.4%), and 1 heart transplantation (0.2%)

– 8 of 21 deaths were sudden cardiac death (SCD) attributable to VRM proved by an autopsy.

The sudden cardiac death data is also interesting because of how these deaths were found. South Korea requires autopsies on deaths that occur soon after vaccine administration as part of their vaccine compensation/liability program. Of the 21 deaths that were attributed to the vaccine, 8 were found to have myocarditis only at autopsy. No one suspected myocarditis in these cases until the autopsy was done. We have no similar mechanism in the US, which means we are not tracking these deaths. This may be convenient for public health authorities who don’t want to answer tough questions, but it doesn’t help citizens or doctors trying to figure out what’s best for individuals and it certainly isn’t helping anyone harmed by the vaccine who turns to the US national vaccine compensation program.

My understanding of the vaccine program in the US is that vaccines that are net positive for the population are approved by the regulatory agencies and then delivered to the populace with the assumption that those few that do end up injured for ‘the greater good’ are compensated from a national fund filled via taxes on the vaccines paid by the vaccine manufacturers. That tax is passed on to those paying for the vaccines, and in the case of the COVID vaccines, that means the generous US taxpayer is funding all of it. The compensation mechanism in part was what being “in this together” was supposed to mean.

But can anyone confidently speak to net benefit of an intervention without quantifying its risks? How many 12-17 year olds should have been enrolled in a trial before approving a drug for this segment of the population ? If you do go ahead and approve a therapy because of an emergency, shouldn’t there be a robust mechanism of adverse event surveillance to allow novel adverse events to be picked up so that the authorities could quickly adjust vaccine recommendations ?

The questions are rhetorical. We don’t actually have a plan for any of this, and if we did have any hope of formulating a plan, the sheer panic from COVID induced in the laptop class destroyed any hope a rational plan would come to be.

COVID risk estimates are always controversial but it was pretty clear early on that even at the worst points of the pandemic the risk of COVID to the young was very, very low. At least one meta-analysis suggested an Infection Fatality Rate (IFR) for ages 0-19 of 0.0003%. From the South Korean Data, the rate of VRM in about the same age range is ~0.004% (80/2M), and the rate of severe vaccine myocarditis is ~0.0008%. If one can safely assume that the IFR of COVID in young people is disproportionately driven by children with severe comorbidities, it is easy to build a case for the rate of vaccine related severe cardiac complications being worse than COVID for young, fit, healthy children even at the outset of the pandemic. To be clear, I don’t think anyone should put tremendous faith in the exact point estimates because these are such rare events but the overall point is that patients and parents may be interested in knowing that even if we could time travel with a vaccine to the early Spring of 2020, the risk of a severe complication from the vaccine in young healthy individuals approximates the risk of dying from COVID. Perhaps you decide vaccination is the right thing for you or your 13 year old after weighing the pros and cons.

Great.

But not having the conversation at all after the Spring of 2021, when the link between myocarditis and the vaccines became firmly established, was a failure on the part of public health officials.

Even worse, vaccine mandates that are still in place (160 US Colleges continue to mandate a vaccine) tie participation in normal society to vaccination and effectively disallow individuals from deciding against vaccination.

The 2023 risk/benefit calculus casts a very long shadow on those who seek to compel their fellow citizens to vaccinate. The vast majority of the population has already received a vaccine or been infected with COVID, and most hospitals in the United States have not seen any significant influx of severe COVID in more than a year. While the Korean data finds a low absolute rate of vaccine myocarditis that ranges from an overall rate of 1/100,000 to a peak rate of 1/18,000 in 12-17 year old boys, it is inexplicable that there remains any appetite for vaccine mandates when 20% of these cases are severe, 4% require a modified heart lung machine, 4% die, 2% suddenly from an arrhythmia.

It’s pretty clear now that the descriptors used for the vaccine for much of the pandemic were hyperbolic and lacked nuance. The vaccines appeared to be very effective in the framework of the trials that were performed at one point and time during the pandemic. Public health, and doctors like me who became vaccine providers needed to be a lot more measured with our assurances about safety of the vaccine. It was hubris and hope that drove the vaccination campaign in the healthy young, and we should have been much more cautious in extrapolating the perceived benefits and risks seen in the early trials of the vaccine to low risk groups.

Moving forward, one would hope the credentialed class that somehow are in charge of nearly every aspect of our life will learn important lessons for the future.

I doubt it.

Anish Koka is a Cardiologist. Follow him on Twitter @anish_koka

I have to make the obligatory post-script here that I oversaw the administration of hundreds of mrna vaccines starting in March of 2021 in my cardiology clinic. The vaccine efficacy data for the original data was from thousands of patients and I certainly felt given the devastation wreaked on many of my patients in 2020 that the vaccines were the best chance of avoiding morbidity and mortality. The process to get the vaccines from the city department of health was a somewhat arduous 3 month process, and once the vaccines were on hand, there were daily reporting requirements that I dutifully performed for the many months we were administering vaccines. To accommodate the rush of patients, employees, volunteers, and conscripted children worked multiple weekends to administer the vaccines. So I’m especially disgusted by medical colleagues who label any concerns registered about vaccine adverse events as “anti-vaxx”. Registering concern over a vaccine adverse event does not make doctors or patients “anti-vaxx”. It makes them pro-vaxx!