Latest survey shows the COVID vaccines are a disaster: ~750,000 dead in US

In US, ~5M people who got the vaccine are now unable to work and ~750,000 are dead. The rate of heart issues is 6.6%, far more than they claimed. No wonder our government isn’t doing these surveys!

Authors: Steve Kirsch Jun 25, 2022

“With over 40 years of experience in genomics, bioinformatics and development of monoclonal, protein therapeutic & small molecule drugs and clinical research on them, there is no question that the complexity of the human body insures that some people will be harmed by them. All drugs are poison at high enough concentration and in many instances drugs that are safe for some are deadly to others. It is evident from the data presented by the FDA Vaccine Adverse Event Registry that the mRNA Jabs have caused millions of injuries. This Study, is a pilot extrapolation that needs further investigation, but, if accurate paints a very troubling picture of harms and future harms caused by these jabs that were not required to demonstrate long-term safety or effectiveness! ”

John Murphy, CEO The COV19 Long-haul Foundation

Executive summary

Our latest poll is devastating for the official narrative:

  1. a 6.6% rate of heart injury (>10M Americans)
  2. 2.7% are unable to work after being vaccinated (>5M Americans),
  3. 6.3% had to be hospitalized (>10M Americans)
  4. you were more likely to die from COVID if you’ve taken the vaccine.
  5. Almost as many (77.4%) households lost someone from the vaccines as from COVID. If you believe that 1M people in the US have died from COVID, then this survey indicates that ~750,000 people died from the vaccine (10.18/13.15*1M) with a 95% confidence of at least 600,000 deaths.

The error bar computation on each question is here.

We will be re-running this with a 5,000 sample size soon which will have smaller error bars. But the key point is that even if we choose the most conservative data points, the survey results are inconsistent with the “safe and effective” narrative.

For example, the CDC hasn’t found anyone who has died from the mRNA vaccines and our survey shows at least 600,000 people have died. That’s a big gap. Someone isn’t telling you the truth. Why do we get such a high number every time we run our poll to a different audience?

Anyone can run our poll for $500 if you don’t believe us. I predict nobody in mainstream media will touch this because they don’t want to know the truth.

This is a poll that nobody who is pro-vaccine wants you to see.

The poll will be ignored by the mainstream media, even when we rerun it with 8,000 people and get the same results. You can bank on that.


We used a professional to draft most of the survey questions and skip logic for our Jun 25 survey.

Here are the key takeaways from the Jun 25 survey. We use “stratified counts” throughout since these are “normalized” based on the US demographics:

  1. 380 of the 500 people who took the poll were vaccinated after normalization [Q1]
  2. Only 34% of Americans are drinking the Kool-Aid and getting >2 doses [Q1]
  3. 2.63% of the households (13.15/500) had someone who died from the COVID virus [Q19]
  4. 2.03% [1.7%-2.4%] of the households (10.18[8.6-11.8]/500) reported a death from the vaccine in their household [Q15]. This is stunning because it shows that the vaccine has killed almost as many people as the COVID virus has. The authorities say that COVID has killed over 1M people in the US so this suggests that 774,000 people were killed by the vaccine (10.18[8.6-11.8]/13.15[12.3-14.0]=77.4% [64.2%-90.5%]). How can that be a “safe” vaccine? The 95% confidence intervals say over 600,000 Americans have been killed by the vaccine. Even if this is overestimated by a factor of 10X, this is devastating for the vaccine narrative. There is simply no way to spin this. This is why the “fact checkers” and mainstream media will avoid this survey.
  5. 2.7% of the people who took the vaccine (10.43/380) are so injured they are unable to work [Q7A2]. This is a disaster. So this is 2.7% of the 200M vaccinated people ages 18 and older: >5M severely injured people who can’t work. I don’t know how they will spin this as a positive.
  6. 16.7% (63.7/380) of the people who took the vaccine consider themselves vaccine injured [Q2]. So that’s >30M vaccine injured. I don’t know how they will spin this as a positive.
  7. The survey shows a 6.6% rate of heart injury post-vaccine according to the poll (24.97/380 [Q3]). This is stunning because these are of the people taking the survey reporting their own injury. Nobody could know this better than the survey taker. This is 1,000X higher than the CDC told us. Per Gavi, “The CDC researchers estimated there might be a maximum of 70 cases of myocarditis out of a million second doses given to boys ages 12 to 17.” How could the CDC underestimate this severe adverse event by 3 orders of magnitude?!!? There is something seriously wrong here. Our survey is well within 1 order of magnitude with other rates we’ve been told. This represents 13.3M million people who are seriously injured, probably for life.
  8. 9.2% (35/380) of the people who took the vaccine had to seek medical help for their injury. [Q4]. That’s 18M doctor visits.
  9. 6.3% (23.83/380) of the people who took the vaccine had to be hospitalized for their vaccine injury [Q5] That’s over 12M hospitalizations.
  10. 3.7% (18.83/500) of the households had a person with a heart condition due to the vaccine [Q14]. Since there are 123M households, this is 4.5M new heart conditions. This is a lower estimate than the direct injury above suggesting that people answering this question were answering it for people other than themselves (since otherwise the rate would be higher than the 6.6% direct rate above). So this is another estimate on the number of new heart conditions.
  11. If you got a COVID infection, it’s 17% (36.4/30.98) [Q17] more likely that you were vaccinated, suggesting the vaccine could be making things worse.
  12. If you died from COVID, it was 72% more likely you died after getting the vaccine (6.81/3.95) [Q22]. We were told the opposite by the government.
  13. 46% are planning on getting more vaccines [Q23]. A total of 24.6% of all people are sheep, i.e., even if they are told the vaccine has a good chance of disabling them for life, they will do what the government recommends. These percentages are approximately what is predicted by mass formation theory.
  14. Most people (65%) believed that the hospital treatments for COVID may be responsible for killing people that they lost to COVID, not COVID [Q20]

The survey and underlying data

Jun 25 survey

  1. Jun 25 Pollfish survey summary
  2. Jun 24 Pollfish survey response detail

Here is the skip logic for the Jun 25 survey

Skip logic for June 25 poll

Earlier survey

  1. Jun 24 Pollfish survey summary
  2. Jun 24 Pollfish survey response detail

Latest survey where we broke out the myocarditis rates

  1. Jun 27 Pollfish survey summary
  2. Jun 27 Pollfish survey response detail

Error bars on the numbers

See this error bar computation.

I put the numbers in for the number of people who died. It’s a disaster even if you are on the low end of the error bars: at least 600,000 deaths from the vaccines.

Even if we are off by 10X, the vaccines are a disaster.


See my earlier article for a description. No change. It was done by a professional polling organization. If you start the first question, you’re counted. You can’t tell anything about the survey from the first question.

The 500 people are chosen at random and designed to represent a cross-section of America.

The poll size is only 500 since these are test runs.

Therefore, the numbers for the final results could be off. I’ve computed the error bars for each question.

But even if all numbers are a factor of 10 lower, this vaccine is still a complete disaster and should be immediately halted.

Fact checkers welcome

We’ll happily do an interactive session where we show you all the data and the poll results so you can verify they weren’t tampered with. You can even reach out to Pollfish to verify the survey results are legit. We have nothing to hide.

We’ll give you the data files so you can run the poll yourself.

But nobody’s going to fact check this because it would just draw attention to it. So they will have to ignore this and pretend it didn’t happen. That’s what fact checkers do when the facts don’t support the narrative they are paid to support.

Next step

We’ll adjust some of the questions again and re-run the survey with another 500.

Then we’ll increase the size to 5,000 people to reduce the error bars from around 4% to 1%.

We’ll have the final results soon, but we already know the results are devastating.


The bottom line is this: the mainstream media, the medical community, public health officials, members of Congress, CDC, the “fact checkers,” or anyone else who is pro-vaccine will never run a poll like this to find out the truth.

They don’t want to know the truth and, more importantly, they don’t want you to know the truth either.

New Study Contradicts ‘Experts’ – Shows Unvaccinated Adults Found “No increase in Myocarditis and Pericarditis” Following COVID Infection

Authors:  Jim Hoft July 8, 2022 Gateway Pundit

A new study from Israel reveals that there was “no increase in the incidence of myocarditis and pericarditis” in unvaccinated adults who had COVID-19 infection.

This contradicts the findings of earlier studies that suggested there may be a connection between cardiac inflammation and coronavirus infections.

In a study published in the Journal of Clinical Medicine, the researchers concluded that there is “no increase in the incidence of myocarditis and pericarditis in COVID-19 recovered patients compared to uninfected matched controls.”

“Myocarditis and pericarditis are potential post-acute cardiac sequelae of COVID-19 infection, arising from adaptive immune responses,” the study stated. “We aimed to study the incidence of post-acute COVID-19 myocarditis and pericarditis.”

A total of 787,968 Clalit Health Services adult members were included in the study between March 2020 and January 2021. Out of that total, 196,992 adults were found to be infected with the COVID-19 virus (16,632 adults with previous vaccination were excluded from the group).

The control cohort of 590,976 adults with no Covid were age- and sex-matched, according to the study (5 adults with previous vaccination were excluded from the group).

“Nine post-COVID-19 patients developed myocarditis (0.0046%), and eleven patients were diagnosed with pericarditis (0.0056%). In the control cohort, 27 patients had myocarditis (0.0046%) and 52 had pericarditis (0.0088%),” the study stated.

“In the current large population study of subjects, who were not vaccinated against SARS-CoV-2, we observed no increase in the incidence of myocarditis or pericarditis from day 10 after positive SARS-CoV-2.”

The researchers went on and stated, “Multivariable analysis did show male sex as associated with a higher risk of developing myocarditis or pericarditis, regardless of previous COVID-19 infection.”

Vaccinated Up to 15X MORE LIKELY Than Unvaxxed to Develop Heart Inflammation Requiring Hospitalization: Peer Reviewed Study

Authors:  Julian Conradson Published April 25, 2022 at 4:14pm

A new study out of Europe has revealed that cases of heart inflammation that required hospitalization were much more common among vaccinated individuals compared to the unvaccinated.

A team of researchers from health agencies in Finland, Denmark, Sweden, and Norway found that rates of myocarditis and pericarditis, two forms of potentially life-threatening heart inflammation, were higher in those who had received one or two doses of either mRNA-based vaccine – Pfizer’s or Moderna’s.

In all, researchers studied a total of 23.1 million records on individuals aged 12 or older between December 2020 and October 2021. In addition to the increased rate overall, the massive study confirmed the chances of developing the heart condition increased with a second dose, which mirrors other data that has been uncovered in recent months.

From the *peer-reviewed study, which was published by the Journal of the American Medical Association (JAMA):

“Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273.

The risks of myocarditis and pericarditis were highest within the first 7 days of being vaccinated, were increased for all combinations of mRNA vaccines, and were more pronounced after the second dose.”

Also mirroring other data, the study confirmed that young people, especially young males, are the ones who are suffering the worst effects of the experimental jab. Young men, aged 16-24 were an astounding 5-15X more likely to be hospitalized with heart inflammation than their unvaccinated peers.

But it isn’t just young men, all age groups across both sexes – except for men over 40 and girls aged 12-15 – experienced a higher rate of heart inflammation post-vaccination when compared to the unvaxxed.

From The Epoch Times, who spoke with one of the study’s main researchers, Dr. Rickard Ljung:

“‘These extra cases among men aged 16–24 correspond to a 5 times increased risk after Comirnaty and 15 times increased risk after Spikevax compared to unvaccinated,’ Dr. Rickard Ljung, a professor and physician at the Swedish Medical Products Agency and one of the principal investigators of the study, told The Epoch Times in an email.

Comirnaty is the brand name for Pfizer’s vaccine while Spikevax is the brand name for Moderna’s jab.

Rates were also higher among the age group for those who received any dose of the Pfizer or Moderna vaccines, both of which utilize mRNA technology. And rates were elevated among vaccinated males of all ages after the first or second dose, except for the first dose of Moderna’s shot for those 40 or older, and females 12- to 15-years-old.”

Although the peer-reviewed study found a direct link between mRNA based vaccines and increased incident rate of heart inflammation, the researchers claimed that the “benefits” of the experimental vaccines still “outweigh the risks of side effects,” because cases of heart inflammation are “very rare,” in a press conference about their findings earlier this month.

However, while overall case numbers may be low in comparison to the raw numbers and thus technically “very rare,” the rate at which individuals are developing this serious condition has increased by a whopping amount. When considering the fact that 5-15X more, otherwise healthy, young men will come down with the condition – especially since the chances of Covid-19 killing them at that age are effectively zero (99.995% recovery rate) – it’s downright criminal for governments across the world to continue pushing mass vaccinations for everyone.

Dr. Peter McCullough, a world-renowned Cardiologist who has been warning about the long-term horror show that is vaccine-induced myocarditis in young people, certainly thinks so. In his expert opinion, the study does anything but give confidence that the benefits of the vaccine outweigh the risks. In “no way” is that the case, he says. Actually, it’s quite the opposite.

From McCullough, via The Epoch Times:

“In cardiology we spend our entire career trying to save every bit of heart muscle. We put in stents, we do heart catheterization, we do stress tests, we do CT angiograms. The whole game of cardiology is to preserve heart muscle. Under no circumstances would we accept a vaccine that causes even one person to stay sustain heart damage. Not one. And this idea that ‘oh, we’re going to ask a large number of people to sustain heart damage for some other theoretical benefit for a viral infection,’ which for most is less than a common cold, is untenable. The benefits of the vaccines in no way outweigh the risks.”

It’s also worth pointing out that the new study’s findings could be an indicator as to what is driving the massive spike in the excess death rates in the United States and across the world. Correlating exactly with the rollout of the experimental mRNA Covid-19 vaccines, people have been dying at record-breaking rates, especially millennials, who experienced a jaw-dropping 84% increase in excess deaths (compared to pre-pandemic) in the final four months of 2021.

With all the data that has been made available up to this point, there is no denying that the vaccine is at least partially to blame for the spike in severe illness and death, if not entirely. Nevertheless, the CDC, Fauci, Biden, and the rest of the corrupt establishment continue to push mass vaccines, just approved another booster jab (with plans for another already in the works), and are licking their chops to unleash another round of Covid hysteria and crippling restrictions come this fall.

SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis

Authors: RALPH TURCHIANO    • 


Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm.

Millennials Experienced the “Worst-Ever Excess Mortality in History” – An 84% Increase In Deaths After Vaccine Mandates

The most recent data from the CDC shows that U.S. millennials, aged 25-44, experienced a record-setting 84% increase in excess mortality during the final four months of 2021, according to the analysis of financial expert and Blackrock whistleblower, Edward Dowd,

Dowd, with the assistance of an insurance industry expert, compiled data from the CDC showing that, in just the second half of 2021, the total number of excess deaths for millennials was higher than the number of Americans who died in the entirety of the Vietnam War. Between August and December, there were over 61,000 deaths in this age group, compared to 58,000 over the course of 10 years in Vietnam.

In all, excess death among those who are traditionally the healthiest Americans is up by 84%.

Colchicine: A Possible COVID-19 Long haul Cardiac Therapy

Last Updated: December 16, 2021

Last Updated: December 16, 2021

Colchicine is an anti-inflammatory drug that is used to treat a variety of conditions, including gout, recurrent pericarditis, and familial Mediterranean fever.1 Recently, the drug has been shown to potentially reduce the risk of cardiovascular events in those with coronary artery disease.2 Colchicine has several potential mechanisms of action, including reducing the chemotaxis of neutrophils, inhibiting inflammasome signaling, and decreasing the production of cytokines, such as interleukin-1 beta.3 When colchicine is administered early in the course of COVID-19, these mechanisms could potentially mitigate or prevent inflammation-associated manifestations of the disease. These anti-inflammatory properties coupled with the drug’s limited immunosuppressive potential, favorable safety profile, and widespread availability have prompted investigation of colchicine for the treatment of COVID-19.


  • The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of colchicine for the treatment of nonhospitalized patients with COVID-19, except in a clinical trial (BIIa).
  • The Panel recommends against the use of colchicine for the treatment of hospitalized patients with COVID-19 (AI).


For Nonhospitalized Patients With COVID-19

COLCORONA, a large randomized placebo-controlled trial that evaluated colchicine in outpatients with COVID-19, did not reach its primary efficacy endpoint of reducing hospitalizations and death.4 However, in the subset of patients whose diagnosis was confirmed by a positive SARS-CoV-2 polymerase chain reaction (PCR) result from a nasopharyngeal (NP) swab, a slight reduction in hospitalizations was observed among those who received colchicine.

PRINCIPLE, another randomized, open-label, adaptive-platform trial that evaluated colchicine versus usual care, was stopped for futility when no significant difference in time to first self-reported recovery from COVID-19 between the colchicine and usual care recipients was found.5

The PRINCIPLE trial showed no benefit of colchicine, and the larger COLCORONA trial failed to reach its primary endpoint, found only a very modest effect of colchicine in the subgroup of patients with positive SARS-CoV-2 PCR results, and reported more gastrointestinal adverse events in those receiving colchicine. Therefore, the Panel recommends against the use of colchicine for the treatment of COVID-19 in nonhospitalized patients, except in a clinical trial (BIIa).

For Hospitalized Patients With COVID-19

In the RECOVERY trial, a large randomized trial in hospitalized patients with COVID-19, colchicine demonstrated no benefit with regard to 28-day mortality or any secondary outcomes.6 Based on the results from this large trial, the Panel recommends against the use of colchicine for the treatment of COVID-19 in hospitalized patients (AI).

Clinical Data for COVID-19

Colchicine in Nonhospitalized Patients With COVID-19


The COLCORONA trial was a contactless, double-blind, placebo-controlled, randomized trial in outpatients who received a diagnosis of COVID-19 within 24 hours of enrollment. Participants were aged ≥70 years or aged ≥40 years with at least 1 of the following risk factors for COVID-19 complications: body mass index ≥30, diabetes mellitus, uncontrolled hypertension, known respiratory disease, heart failure or coronary disease, fever ≥38.4°C within the last 48 hours, dyspnea at presentation, bicytopenia, pancytopenia, or the combination of high neutrophil count and low lymphocyte count. Participants were randomized 1:1 to receive colchicine 0.5 mg twice daily for 3 days and then once daily for 27 days or placebo. The primary endpoint was a composite of death or hospitalization by Day 30; secondary endpoints included components of the primary endpoint, as well as the need for mechanical ventilation by Day 30. Participants reported by telephone the occurrence of any study endpoints at 15 and 30 days after randomization; in some cases, clinical data were confirmed or obtained by medical chart reviews.4


  • The study enrolled 4,488 participants.
  • The primary endpoint occurred in 104 of 2,235 participants (4.7%) in the colchicine arm and 131 of 2,253 participants (5.8%) in the placebo arm (OR 0.79; 95% CI, 0.61–1.03; P = 0.08).
  • There were no statistically significant differences in the secondary outcomes between the arms.
  • In a prespecified analysis of 4,159 participants who had a SARS-CoV-2 diagnosis confirmed by PCR testing of an NP specimen (93% of those enrolled), those in the colchicine arm were less likely to reach the primary endpoint (96 of 2,075 participants [4.6%]) than those in the placebo arm (126 of 2,084 participants [6.0%]; OR 0.75; 95% CI, 0.57–0.99; P = 0.04). In this subgroup of patients with PCR-confirmed SARS-CoV-2 infection, there were fewer hospitalizations (a secondary outcome) in the colchicine arm (4.5% of patients) than in the placebo arm (5.9% of patients; OR 0.75; 95% CI, 0.57–0.99).
  • More participants in the colchicine arm experienced gastrointestinal adverse events, including diarrhea which occurred in 13.7% of colchicine recipients versus 7.3% of placebo recipients (P < 0.0001). Unexpectedly, more pulmonary emboli were reported in the colchicine arm than in the placebo arm (11 events [0.5% of patients] vs. 2 events [0.1% of patients]; P= 0.01).


  • Due to logistical difficulties with staffing, the trial was stopped at approximately 75% of the target enrollment, which may have limited the study’s power to detect differences for the primary outcome.
  • There was uncertainty as to the accuracy of COVID-19 diagnoses in presumptive cases.
  • Some patient-reported clinical outcomes were potentially misclassified.


PRINCIPLE is a randomized, open-label, platform trial that evaluated colchicine in symptomatic, nonhospitalized patients with COVID-19 who were aged ≥65 years or aged ≥18 years with comorbidities or shortness of breath, and who had symptoms for ≤14 days. Participants were randomized to receive colchicine 0.5 mg daily for 14 days or usual care. The coprimary endpoints, which included time to first self-reported recovery or hospitalization or death due to COVID-19 by Day 28, were analyzed using a Bayesian model. Participants were followed through symptom diaries that they completed online daily; those who did not complete the diaries were contacted by telephone on Days 7, 14, and 29. The investigators developed a prespecified criterion for futility, specifying a clinically meaningful benefit in time to first self-reported recovery as a hazard ratio ≥1.2, corresponding to about 1.5 days of faster recovery in the colchicine arm.


  • The study enrolled 4,997 participants: 212 participants were randomized to receive colchicine; 2,081 to receive usual care alone; and 2,704 to receive other treatments.
  • The prespecified primary analysis included participants with SARS-CoV-2 positive test results (156 in the colchicine arm; 1,145 in the usual care arm; and 1,454 in the other treatments arm).
  • The trial was stopped early because the criterion for futility was met; the median time to self-reported recovery was similar in the colchicine arm and the usual care arm (HR 0.92; 95% CrI, 0.72–1.16).
  • Analyses of self-reported time to recovery and hospitalizations or death due to COVID-19 among concurrent controls also showed no significant differences between the colchicine and usual care arms.
  • There were no statistically significant differences in the secondary outcomes between the colchicine and usual care arms in both the primary analysis population and in subgroups, including subgroups based on symptom duration, baseline disease severity, age, or comorbidities.
  • The occurrence of adverse events was similar in the colchicine and usual care arms.


  • The design of the study was open-label treatment.
  • The sample size of the colchicine arm was small.

Colchicine in Hospitalized Patients With COVID-19


In the RECOVERY trial, hospitalized patients with COVID-19 were randomized to receive colchicine (1 mg loading dose, followed by 0.5 mg 12 hours later, and then 0.5 mg twice daily for 10 days or until discharge) or usual care.6


  • The study enrolled 11,340 participants.
  • At randomization, 10,603 patients (94%) were receiving corticosteroids.
  • The primary endpoint of all-cause mortality at Day 28 occurred in 1,173 of 5,610 participants (21%) in the colchicine arm and 1,190 of 5,730 participants (21%) in the placebo arm (rate ratio 1.01; 95% CI, 0.93–1.10; P = 0.77).
  • There were no statistically significant differences between the arms for the secondary outcomes of median time to being discharged alive, discharge from the hospital within 28 days, and receipt of mechanical ventilation or death.
  • The incidence of new cardiac arrhythmias, bleeding events, and thrombotic events was similar in the 2 arms. Two serious adverse events were attributed to colchicine: 1 case of severe acute kidney injury and one case of rhabdomyolysis.


  • The trial’s open-label design may have introduced bias for assessing some of the secondary endpoints.

The GRECCO-19 Trial

GRECCO-19 was a small, prospective, open-label randomized clinical trial in 105 patients hospitalized with COVID-19 across 16 hospitals in Greece. Patients were assigned 1:1 to receive standard of care with colchicine (1.5 mg loading dose, followed by 0.5 mg after 60 minutes and then 0.5 mg twice daily until hospital discharge or for up to 3 weeks) or standard of care alone.7


  • Fewer patients in the colchicine arm (1 of 55 patients) than in the standard of care arm (7 of 50 patients) reached the primary clinical endpoint of deterioration in clinical status from baseline by 2 points on a 7-point clinical status scale (OR 0.11; 95% CI, 0.01–0.96).
  • Participants in the colchicine group were significantly more likely to experience diarrhea (occurred in 45.5% of participants in the colchicine arm vs. 18.0% in the standard of care arm; P = 0.003).


  • The overall sample size and the number of clinical events reported were small.
  • The study design was open-label treatment assignment.

The results of several small randomized trials and retrospective cohort studies that have evaluated various doses and durations of colchicine in hospitalized patients with COVID-19 have been published in peer-reviewed journals or made available as preliminary, non-peer-reviewed reports.8-11 Some have shown benefits of colchicine use, including less need for supplemental oxygen, improvements in clinical status on an ordinal clinical scale, and reductions in certain inflammatory markers. In addition, some studies have reported higher discharge rates or fewer deaths among patients who received colchicine than among those who received comparator drugs or placebo. However, the findings of these studies are difficult to interpret due to significant design or methodological limitations, including small sample sizes, open-label designs, and differences in the clinical and demographic characteristics of participants and permitted use of various cotreatments (e.g., remdesivir, corticosteroids) in the treatment arms.

Adverse Effects, Monitoring, and Drug-Drug Interactions

Common adverse effects of colchicine include diarrhea, nausea, vomiting, abdominal cramping and pain, bloating, and loss of appetite. In rare cases, colchicine is associated with serious adverse events, such as neuromyotoxicity and blood dyscrasias. Use of colchicine should be avoided in patients with severe renal insufficiency, and patients with moderate renal insufficiency who receive the drug should be monitored for adverse effects. Caution should be used when colchicine is coadministered with drugs that inhibit cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp) because such use may increase the risk of colchicine-induced adverse effects due to significant increases in colchicine plasma levels. The risk of myopathy may be increased with the concomitant use of certain HMG-CoA reductase inhibitors (e.g., atorvastatin, lovastatin, simvastatin) due to potential competitive interactions mediated by CYP3A4 and P-gp pathways.12,13 Fatal colchicine toxicity has been reported in individuals with renal or hepatic impairment who received colchicine in conjunction with P-gp inhibitors or strong CYP3A4 inhibitors.

Considerations in Pregnancy

There are limited data on the use of colchicine in pregnancy. Fetal risk cannot be ruled out based on data from animal studies and the drug’s mechanism of action. Colchicine crosses the placenta and has antimitotic properties, which raises a theoretical concern for teratogenicity. However, a recent meta-analysis did not find that colchicine exposure during pregnancy increased the rates of miscarriage or major fetal malformations. There are no data for colchicine use in pregnant women with acute COVID-19. Risks of use should be balanced against potential benefits.12,14

Considerations in Children

Colchicine is most commonly used in children to treat periodic fever syndromes and autoinflammatory conditions. Although colchicine is generally considered safe and well tolerated in children, there are no data on the use of the drug to treat pediatric acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C).


  1. van Echteld I, Wechalekar MD, Schlesinger N, Buchbinder R, Aletaha D. Colchicine for acute gout. Cochrane Database Syst Rev. 2014(8):CD006190. Available at:
  2. Xia M, Yang X, Qian C. Meta-analysis evaluating the utility of colchicine in secondary prevention of coronary artery disease. Am J Cardiol. 2021;140:33-38. Available at:
  3. Reyes AZ, Hu KA, Teperman J, et al. Anti-inflammatory therapy for COVID-19 infection: the case for colchicine. Ann Rheum Dis. 2021 May;80(5):550-557. Available at:
  4. Tardif JC, Bouabdallaoui N, L’Allier PL, et al. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med. 2021;9(8):924-932. Available at:
  5. PRINCIPLE Trial Collaborative Group, Dorward J, Yu L, et al. Colchicine for COVID-19 in adults in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial. medRxiv. 2021;Preprint. Available at:
  6. RECOVERY Collaborative Group. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet Respir Med. 2021;Published online ahead of print. Available at:
  7. Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial. JAMA Netw Open. 2020;3(6):e2013136. Available at:
  8. Brunetti L, Diawara O, Tsai A, et al. Colchicine to weather the cytokine storm in hospitalized patients with COVID-19. J Clin Med. 2020;9(9). Available at:
  9. Sandhu T, Tieng A, Chilimuri S, Franchin G. A case control study to evaluate the impact of colchicine on patients admitted to the hospital with moderate to severe COVID-19 infection. Can J Infect Dis Med Microbiol. 2020. Available at:
  10. Lopes MI, Bonjorno LP, Giannini MC, et al. Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial. RMD Open. 2021;7(1). Available at:
  11. Salehzadeh F, Pourfarzi F, Ataei S. The impact of colchicine on the COVID-19 patients; a clinical trial. Research Square. 2020;Preprint. Available at:
  12. Colchicine (Colcrys) [package insert]. Food and Drug Administration. 2012. Available at:
  13. American College of Cardiology. AHA statement on drug-drug interactions with statins. 2016. Available at: Accessed November 2, 2021.
  14. Indraratna PL, Virk S, Gurram D, Day RO. Use of colchicine in pregnancy: a systematic review and meta-analysis. Rheumatology (Oxford). 2018;57(2):382-387. Available at:

www.covid19treatmentguidelines.nih.govAn official website of the National Institutes of Health

The Role of Colchicine in Pericardial Syndromes

Authors: George Lazaros 1Massimo Imazio 2Antonio Brucato 3Charalambos Vlachopoulos 1Emilia Lazarou 1Dimitrios Vassilopoulos 4Dimitris Tousoulis 1PMID: 29336245

DOI: 10.2174/1381612824666180116101823 Curr Pharm Des . 2018;24(6):702-709. doi: 10.2174/1381612824666180116101823.


Background: Colchicine is an old drug originally employed for the treatment of inflammatory disorders such as acute gout and familiar Mediterranean fever.

Methods: In the past few decades, colchicine has been at the forefront of the pharmacotherapy of several cardiac diseases, including acute and recurrent pericarditis, coronary artery disease, prevention of atrial fibrillation and heart failure. In this review, we have summarized the current evidence based medicine and guidelines recommendations in the specific context of pericardial syndromes.

Results: Colchicine has been firstly engaged in the treatment of recurrent pericarditis of viral, idiopathic and autoimmune origin. Shortly thereafter colchicine use has been expanded to the primary prevention of recurrences in patients with a first episode of pericarditis depicting similarly good results. The acquisition of high quality scientific data in the course of time from prospective randomized placebo-controlled trials and metanalyses have established colchicine as first line treatment option in acute and recurrent pericarditis, on top of the conventional treatment. The only concerns related to the use of colchicine are the side effects (mainly gastrointestinal intolerance) which although generally not serious, may account for treatment withdrawal in some cases.

Conclusion: Colchicine has been established as a first line medication in the treatment of acute (first episode) and recurrent pericarditis on top of the conventional treatment as well as for the prevention of postpericardiotomy syndrome. It depicts a good safety profile with gastrointestinal intolerance being the most common side effect.

Acute pericarditis as a primary presentation of COVID-19


The COVID-19 pandemic is a highly contagious viral illness which conventionally manifests primarily with respiratory symptoms. We report a case whose first manifestation of COVID-19 was pericarditis, in the absence of respiratory symptoms, without any serious complications. Cardiac involvement in various forms is possible in COVID-19. We present a case where pericarditis, in the absence of the classic COVID-19 signs or symptoms, is the only evident manifestation of the disease. This case highlights an atypical presentation of COVID-19 and the need for a high index of suspicion to allow early diagnosis and limit spread by isolation.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.


The global COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2, an enveloped single-stranded RNA virus of zoonotic origin. Transmission is mainly by aerosolised droplet contact, although surface fomite contact and faecal transmission are reported. Symptoms of coronavirus include high-grade fever, severe cough and breathlessness. Cytokine induction causes heavy neutrophilia in the alveoli, with capillaritis, fibrin deposition and thick mucositis causing respiratory failure, acute lung injury and death. Conversely approximately one in eight patients are estimated to have an entirely benign course, transmitting the virus with no clinical manifestation of the disease.1 2 Chest pain in COVID-19 may have cardiac causes, including acute coronary syndrome, pericarditis and myocarditis.3 We present the first described case of acute pericarditis in the absence of initial respiratory symptoms secondary to COVID-19.

Case presentation

A 66-year-old farmer was admitted with 1-day history of acute-onset severe pleuritic chest pain, with four episodes lasting 10–15 min. The pain was worse when lying flat and relieved by leaning forward. He had no sweating nor fever. His history includes Crohn’s disease, hypertension and benign prostatic hyperplasia. His medications were esomeprazole, ramipril and tamsulosin. He had a 40 pack-year smoking history and a significant familial premature coronary disease. His vaccination schedule was up to date, and he had not travelled recently. On examination his temperature was 36.9°C, blood pressure was 134/83 mm Hg, heart rate was 86 beats/min, respiratory rate was 16 breaths/min and an O2 saturation of 99% on ambient air. His general, cardiovascular and respiratory examinations were normal.


Full blood count, urea and electrolytes, coagulation profile, and liver function tests were normal. His C reactive protein (CRP) was 7 mg/L (normal <5 mg/L). High sensitivity cardiac troponin T (hs-cTnT) on admission and at 6 hours were 10 ng/L and 13 ng/L, respectively (normal <14 ng/L). His ECG showed ST segment elevation in most leads with PR interval depression, and his chest X-ray (CXR) confirmed clear lungs with no abnormality (figure 1). Transthoracic echocardiogram (TTE) confirmed normal structure and function, although his pericardium was echo bright with no pericardial effusion (figure 2). CT of the thorax, abdomen and pelvis was normal.

Figure 1

Figure 1

Admission ECG and chest X-ray on day 1. There is minimal ST segment elevation in most leads with PR interval depression.

Figure 2

Figure 2

Transthoracic echocardiogram showing brightened pericardium (white arrows) with no effusion.

Serum, nasopharyngeal and oropharyngeal swab specimen samples were sent for aetiological viruses associated with pericarditis. However, the patient presented in February 2020, which was early in the chronology of COVID-19 in Ireland and he did not have routine COVID-19 screening swabs. Complement levels, erythrocyte sedimentation rate and connective tissue screens were negative. Nucleic acid amplification tests for influenza A and B were negative. Cardiac MRI (cMRI) with adenosine stress perfusion showed a structurally normal heart with no effusion, fibrosis, infarction or infiltration. No inducible perfusion defects were evident during adenosine stress. His pericardium appeared mildly thickened (figure 3).

Figure 3

Figure 3

Cardiac MRI of the patient with perfusion showing normal left ventricle muscle (black arrows). The pericardium, pointed by white arrows, shows mild thickening (bold white) with no effusion.

Differential diagnosis

Differential diagnoses included myocarditis, acute coronary syndrome, pericarditis or pleuritis.


A diagnosis of pericarditis was made based on typical chest pain, ECG presentation and TTE. He was started on oral colchicine two times per day for 2 weeks and was discharged on day 4.

Outcome and follow-up

The patient was readmitted on day 6 with recurrence of intermittent pleuritic chest pain and dry cough. Vital signs, physical examination and blood tests were normal. CXR and ECG remained unchanged. Viral serology was negative for routine viruses associated with pericarditis. A COVID-19 viral PCR nasopharyngeal swab was positive.

The public health team was notified and the patient was isolated. On day 8 he developed upper respiratory tract symptoms with peak temperature of 38.7°C. Lymphopaenia (0.3×109, normal >1×109/L) with normal interleukin-6 (5.77, normal 0.09–7.26 pg/mL), CRP and hs-cTnT were seen. Blood culture showed no growth, and serial CXR remained normal. He recovered with symptomatic treatment and oral colchicines and was discharged on day 12.


COVID-19 has numerous adverse effects on the cardiovascular system. Cardiac injury with troponin leak is associated with increased mortality in COVID-19, and its clinical and radiographic features are difficult to distinguish from those of heart failure.4–6 One reported COVID-19 case with upper respiratory tract symptoms had haemorrhagic pericardial effusion with tamponade.7 To our knowledge this is the first case where COVID-19 presents as pericarditis, in the absence of evident respiratory or myocardial involvement.

Acute pericarditis is the most common disease of the pericardium and is responsible for 0.2% of chest pain-related hospitalisations. Conversely 40%–85% of pericarditis cases are of unknown aetiology, probably due to difficulty in obtaining diagnostic pericardial samples. It is commonly seen in viral infections, including coxsackie, enterovirus, herpes simplex, cytomegalovirus, H1N1, respiratory syncytial virus, parvovirus B19, influenza, varicella, HIV, rubella, echovirus, and hepatitis B and C, although the viruses responsible in a given patient may be different genotypes of the same virus or different coexistent viruses.8 9

In this patient respiratory swabs were initially negative, and viraemia first manifested with dry pericarditic symptoms, with a later diagnosis of COVID-19. Defining the underlying causative virus is not always possible. Serological tests are only suggestive of a diagnosis of pericarditis and may yield false negative results. Pericardial inflammation may prompt symptoms, yet may precede the generation of an observable pericardial effusion. TTE is recommended to exclude significant effusion, although the absence of fluid does not rule out active pericarditis. cMRI can describe pericardial thickening or small effusions, which are not appreciated on TTE, assess for myocarditis on T2-weighted imaging, define pericardial inflammation on late gadolinium phase and quantify systolic function.10 Pericardiocentesis is the gold standard for definition of the underlying cause, providing a sufficient depth of fluid at a favourable angle is seen on TTE, although this carries associated risk of serious cardiac injury and a clinical diagnosis may be made if other supportive features are present.

Acute pericarditis is usually self-limiting, although it recurs in up to 30% of cases. Most patients recover in 2–4 weeks with supportive measures, which would conventionally include non-steroidal anti-inflammatory drugs (NSAIDs), colchicines and treating the causative disease. Applying this to a patient with COVID-19 requires balancing this conventional approach with an emerging understanding of pharmacotherapy in COVID-19. Colchicine inhibits microtubule, cell adhesion molecule and inflammasome activity, and is of use in preventing relapse in pericarditis at first presentation.11 It is being trialled as a potential therapeutic anticytokine agent in COVID-19 in Italy, with one report of its use being associated with improvement.12 Conversely the use of NSAIDs in COVID-19 may be harmful, with previously recognised increased risks of stroke and myocardial infarction (MI) with NSAIDs in acute respiratory infections raising concerns. No effective respiratory benefit has been seen with glucocorticoid use in COVID-19, although their use in pericarditis may promote relapse.13 14

Currently, our understanding of the transmission dynamics and the spectrum of clinical illness of COVID-19 is limited. Cardiac involvement with various ECG presentations is possible and clinicians all across the globe need to be aware of this possibility. This case highlights the importance of recognising COVID-19 infection with atypical clinical presentations such as pericarditis and non-specific ECG changes, and coordination with healthcare team regarding prompt isolation to decrease the risk of transmission of the virus and if any need of early hospitalisation. This case report is helpful in treating patients with this unique clinical presentation.

Patient’s perspective

I woke up one day and I had a nagging pain in the center of my chest, which I never had or felt before, sharp like a knife and pressure on top of it as well. It was a constant nagging pain. It was relieving when I was sitting forward and back worsened as I was lying down in the bed. I felt more weak that day and had no energy. Then pain got a bit worse at midday and my wife advised me to visit my doctor -general practitioner as a felt weak. After my doctor saw me, he advised me to go to the hospital and get myself check out to make sure I am not having a heart attack. I and my wife got very nervous. We came urgent to hospital emergency where a nurse examined me first, followed by a doctor and suggested they don’t think that I am having a heart attack. He referred me to heart expert, who suggested that I have to be admitted in the hospital for more tests. They kept me for three days and all my tests like chest and body scans and bloods suggested that I have inflammation around the layers of heart. I was given some medication and discharged home that it will get better in a few days. I went home, the pain was there, it didn’t went completely but improved slightly. It was worse with lying down in the bed. It wasn’t going away despite me doing all what I was told for next few days. I came back to emergency department in 1st march as the pain wasn’t settling at all with the medication. I went through all this process again. I was isolated, swabbed my nose for this new virus-COVID-19. I did not had any sick contact or any other viral contact. I was nervous, and the result came positive. I was kept in separate part of hospital with no direct visitors to me and my family called me on the phone. I thought I am going to die but all the doctors and nurses reassured me. I developed slight cough and flu like illness for 2 days and then I got better next few days and I came home. I was told to follow strict isolation and precautions. No issues since discharge feeling very well. It’s an unpleasant experience to be part of virus and I thought I won’t make it as there was uncertainty about future events. I am greatly thankful to all the team who were involved in my care.

Learning points

  • Pericarditis is a potential presentation of COVID-19.
  • COVID-19 can have an atypical presentation with non-respiratory symptoms.
  • Recognition of an atypical symptom of COVID-19 allows for early isolation and limits the spread.


  1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506.doi:10.1016/S0140-6736(20)30183-5pmid: Scholar
  2. Zhu J, Ji P, Pang J, et al. Clinical characteristics of 3062 COVID‐19 patients: a meta‐analysis. J Med Virol 2020;54. doi:doi:10.1002/jmv.25884. [Epub ahead of print: 15 Apr 2020].Google Scholar
  3. Hu H, Ma F, Wei X, et al. Coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin. Eur Heart J 2020. doi:doi:10.1093/eurheartj/ehaa190. [Epub ahead of print: 16 Mar 2020].pmid: Scholar
  4. Han Y. Initial COVID-19 affecting cardiac patients in China. Eur Heart J 2020;41:1719.  doi:10.1093/eurheartj/ehaa257pmid: Scholar
  5. Inciardi RM, Lupi L, Zaccone G, et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020. doi:doi:10.1001/jamacardio.2020.1096. [Epub ahead of print: 27 Mar 2020].pmid: Scholar
  6. Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020. doi:doi:10.1001/jamacardio.2020.0950. [Epub ahead of print: 25 Mar 2020].pmid: Scholar
  7. Dabbagh MF, Aurora L, D’Souza P, et al. Cardiac tamponade secondary to COVID-19. JACC Case Rep 2020;2:1326–30.doi:10.1016/j.jaccas.2020.04.009 pmid: /32328588PubMedGoogle Scholar
  8. Fancello L, Monteil S, Popgeorgiev N, et al. Viral communities associated with human pericardial fluids in idiopathic pericarditis. PLoS One 2014;9:e93367. doi:10.1371/journal.pone.0093367 pmid: Scholar
  9. Kytö V, Sipilä J, Rautava P. Clinical profile and influences on outcomes in patients hospitalized for acute pericarditis. Circulation 2014;130:1601–6.doi:10.1161/CIRCULATIONAHA.114.010376 pmid: Full TextGoogle Scholar
  10. Koos R, Schröder J, Kühl HP. Acute viral pericarditis without typical electrocardiographic changes assessed by cardiac magnetic resonance imaging. Eur Heart J 2009;30:2844.  doi:10.1093/eurheartj/ehp407mid: Scholar
  11. Bayes-Genis A, Adler Y, de Luna AB, et al. Colchicine in pericarditis. Eur Heart J 2017;38:1706–9.doi:10.1093/eurheartj/ehx246pmid: Scholar
  12. Gandolfini I, Delsante M, Fiaccadori E, et al. COVID-19 in kidney transplant recipients. Am J Transplant 2020.Google Scholar
  13. Perricone C, Triggianese P, Bartoloni E, et al. The anti-viral facet of anti-rheumatic drugs: lessons from COVID-19. J Autoimmun 2020;111:102468.  doi:10.1016/j.jaut.2020.102468 pmid: Scholar
  14. Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China. Clin Immunol 2020;214:108393. doi:10.1016/j.clim.2020.108393 pmid: CrossRefPubMedGoogle Scholar

Colchicine Treatment for Recurrent Pericarditis

A Decade of Experience

Authors: Y. AdlerY. FinkelsteinJ. GuindoA. Rodriguez de la SernaY. ShoenfeldA. Bayes-GenisA. SagieA. Bayes de Luna and D. H. SpodickOriginally published2 Jun 1998 Circulation. 1998;97:2183–2185


Background—The most troublesome complication of acute pericarditis is recurrent episodes of pericardial inflammation, occurring in 15% to 32% of cases. The cause of the recurrence is usually unknown, although in some cases it may be traced to viral infection or may be a consequence of coronary artery bypass grafting. The optimal method for prevention has not been fully established; accepted modalities include nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressive agents, and pericardiectomy.

Methods and Results—Based on the proven efficacy of colchicine therapy for familial Mediterranean fever (recurrent polyserositis), several small studies have used colchicine successfully to prevent recurrence of acute pericarditis after failure of conventional treatment. Recently, we reported the results from the largest multicenter international study on 51 patients who were treated with colchicine to prevent further relapses and who were followed up for ≤10 years.

Conclusions—In light of new trial data that have accumulated in the past decade, we review the evidence for the efficacy and safety of colchicine for the prevention of recurrent episodes of pericarditis. Clinical and personal experience shows that colchicine may be an extremely promising adjunct to conventional treatment and may ultimately serve as the initial mode of treatment, especially in idiopathic cases.

Acute inflammation of the pericardium is usually of idiopathic etiology, but it may also be secondary to systemic infection, acute myocardial infarction, cardiac contusion, and autoimmune diseases.1

The most troublesome complication of acute pericarditis is the development of recurrent episodes of pericardial inflammation, occurring in 15% to 32% of cases.2345 Recurrent pericarditis is, in most cases, idiopathic. The pathophysiological process may involve the immune system6,7: high titers of anti-myocardial antibodies have been found in post–open heart surgery patients with acute pericarditis. The optimal method for preventing recurrences has not been established. Therapeutic modalities are nonspecific and include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, immunosuppressive agents, and pericardiectomy.18 Relapses may also occur during reduction of drug doses (incessant pericarditis) or at varying intervals after discontinuation of treatment (recurrent pericarditis).9 Because treatment is often difficult and recurrences may occur over a period of many years,10 constant efforts are being directed toward establishing better means for prevention. In light of recent trial data, we will review the evidence supporting the use of colchicine in preventing recurrent episodes of pericarditis.

On the basis of proven efficacy of colchicine in preventing relapses of systemic inflammatory processes in familial Mediterranean fever (recurrent polyserositis),1112 Rodriguez de la Serna and colleagues13 suggested in 1987 that colchicine be used to prevent recurrences of acute pericarditis. They reported on 3 patients who had recurrent pericarditis (2 idiopathic and 1 with systemic lupus erythematosus), despite adequate treatment with corticosteroids. All were treated with colchicine (1 mg/d) with tapering of the corticosteroids within 2 months. There were no relapses throughout the follow-up period of 15 to 35 months.

In a later prospective study, Guindo and colleagues14 reported on 9 patients (5 idiopathic, 2 post–open heart surgery, 1 with Dressler’s syndrome, and 1 with systemic lupus erythematosus) in whom NSAIDs and corticosteroids failed to prevent relapses of pericarditis (mean of 4.3 episodes per patient). All were treated with combined prednisone (20 to 60 mg/d), which was tapered and discontinued within 6 weeks, and colchicine (1 mg/d). Chest pain was effectively relieved, and no recurrences of pericarditis were noted within a 10- to 54-month follow-up period.

Adler and coworkers10 reported on 8 patients with recurrent pericarditis (5 idiopathic, 2 post–open heart surgery, 1 post chest trauma) who had not responded to NSAIDs (6 patients), corticosteroids (7 patients), and pericardiocentesis (3 patients). All responded to colchicine (1 mg/d) and corticosteroids. The corticosteroids were discontinued within 2 to 6 months, and no recurrences were noted during the 18 to 34 months of follow-up. This result contrasts with a total of 26 relapses in these 8 patients before the introduction of colchicine. Four patients in whom colchicine had been withdrawn because of noncompliance or mild gastrointestinal side effects experienced a relapse within 1 to 12 weeks. With reinstitution of colchicine therapy, they remained symptom-free for the 15 to 24 months of follow-up.

Millaire and coworkers15 reported on 19 patients who had recurrent pericarditis and were treated with colchicine (loading dose of 3 mg/d, reduced to 1 mg/d). Fourteen had no recurrences during a follow-up period of 32 to 44 months. In 4 others, relapses were successfully treated with NSAIDs, and these patients remained symptom-free for an additional 11 to 37 months. Only 1 patient had multiple relapses and needed corticosteroids. The authors concluded that colchicine was an effective alternative therapy for recurrent pericarditis and might even replace corticosteroids. In another report by Adler et al,16 colchicine totally prevented relapses in 56% of patients with previous episodes (range, 2 to 15 attacks) in a long-term follow-up (mean, 36 months per patient) study, and when relapses did occur, they were usually mild and easily controlled without steroids. These researchers suggested that colchicine might even serve as the initial mode of therapy for recurrent pericarditis, because most of the patients who experienced relapses after the institution of colchicine or its withdrawal were those who had previously been treated with corticosteroids.16 Indeed, several studies have found that corticosteroids may have severe side effects and lead to new recurrences of pericarditis or prolong disease duration.17181920 Thus, colchicine may also have a role in facilitating their tapering-off process.9 Still, some authors doubt the efficacy of colchicine because a double-blind, controlled study on the subject is difficult to perform.21 It was for this reason that Fowler and Harbin22 examined the natural history of recurrent pericarditis to determine the frequency of spontaneous remissions. Of the 31 patients included in their study, only 8 had a remission period that exceeded 1 year; in 5 of the 8, remission exceeded 2 years.

A partial answer to these doubts may be found in the largest multicenter study on recurrent pericarditis and colchicine published to date.23 Fifty-one affected patients (36 men and 15 women; mean±SD age, 40.8±18.7 years) who were treated with colchicine to prevent further relapses were followed up for ≤10 years (range, 6 to 128 months; mean, 36.0 months). The pericarditis was idiopathic in 33 patients and secondary in 18. Despite treatment with NSAIDs (n=47), corticosteroids (n=29), pericardiocentesis (n=8), or some combination thereof, 187 recurrences (mean, 3.58±3.64; range, 2 to 15) were noted before colchicine therapy was initiated, with a mean interval between crises of 2.0 months (range, 0.5 to 19 months). During 1004 patient-months of colchicine treatment, only 7 of 51 patients (13.7%) presented with new recurrences. Colchicine was discontinued in 39 patients, and 14 of them (35.8%) experienced relapses. These recurrences were generally minor and were effectively controlled in all patients by the reinstitution of colchicine therapy, sometimes with a dose adjustment of the drug (≤2 mg/d). Gastrointestinal side effects were mild (diarrhea and nausea) and resolved in all patients. During the 2333 patient-months of follow-up, 31 patients (60.7%) remained recurrence-free. Comparison of the symptom-free periods before and after colchicine treatment yielded significant statistical differences (3.1±3.3 versus 43.0±35.0 months, P<0.0001). The authors concluded that colchicine was effective and safe for the long-term prevention of recurrent pericarditis.

The exact mechanism whereby colchicine prevents recurrences of pericarditis is still not fully understood. Colchicine has been used for several centuries as an anti-inflammatory agent for acute arthritis and is the most specific known treatment for acute attacks of gout. Colchicine binds to tubulin, blocks mitosis,9 and inhibits a variety of functions of polymorphonuclear leukocytes both in vivo and in vitro.24 Colchicine also interferes with the transcellular movement of collagen.25 The close proximity of lymphoid components and fibroblasts at inflammatory sites and the production of lymphokines, which influence fibroblast chemotaxis, proliferation, and protein synthesis, are now well recognized.26 Thus, colchicine may reduce immunopathic antifibroblastic properties. The peak concentration of colchicine in white blood cells may be ≥16 times the peak concentration in plasma. This preferential concentration of colchicine in lymphocytes is related to its observed therapeutic effect.27

Cumulative anecdotal evidence indicates that colchicine may also be effective in the treatment of the initial episodes of acute pericarditis. Millaire and Durlaux,28 in a study of 19 patients, described the efficacy of colchicine for the first episode of acute pericarditis, especially when it was idiopathic, viral, or post–open heart surgery. Colchicine effectively controlled the acute phase of pericarditis in almost all cases. Only two relapses were noted in a mean follow-up period of 5 months (range, 1 to 12 months), one due to discontinuation of treatment after 8 days and the other due to noncompliance.

Recently, we examined the usefulness of colchicine for the treatment of large pericardial effusions as complications of idiopathic pericarditis.29 Colchicine (1 mg/d) was administered to two patients (26 and 2 years old) with large acute or chronic pericardial effusions who did not respond well to therapy with NSAIDs, corticosteroids, and pericardiocentesis. Response was immediate and dramatic in both cases, with disappearance of the pericardial effusion on echocardiography. Neither patient suffered a relapse during the respective 24 and 6 months of follow-up.

In addition to its apparently greater efficacy compared with corticosteroids,916 colchicine may also have a sparing effect on steroids, which have severe systemic side effects over time and may prolong disease duration.17181920 Furthermore, immunosuppressive drugs and pericardiectomy are generally not appropriate and may even be life threatening,21 whereas colchicine is usually well tolerated, with only minor side effects. During a total of 1004 patient-months of colchicine treatment (mean, 12 months per patient), temporary discontinuation of the drug or a reduction of its dose was needed in only 7 of 51 patients (13.7%).23 This was due to mild gastrointestinal side effects (diarrhea and nausea) in all cases, which are the common drawbacks of colchicine therapy. Drug toxicity with respect to long-term administration of colchicine might be estimated from familial Mediterranean fever or gout patients. Azoospermia and chromosomal abnormalities have been reported with long-term treatment,30 but these findings are debatable.

In conclusion, colchicine seems to be an effective and safe agent for the prevention of recurrent episodes of pericarditis. Colchicine is an extremely promising adjunct to the conventional treatment of recurrent pericarditis and may ultimately serve as the initial mode of treatment, especially in idiopathic cases. Considering that recurrent pericarditis is not life threatening and that long-term treatment is aimed at improving the quality of life, we suggest that corticosteroids should be limited to very severe cases. Milder cases may initially be treated with colchicine as well as with NSAIDs (ibuprofen). The recommended dose of colchicine according to most studies is 1 mg/d for at least 1 year, with a gradual tapering off. The need for a loading dose of 2 to 3 mg/d at the beginning of treatment is unclear. The drug is well tolerated. Gastrointestinal side effects develop in only a small proportion of patients, are usually minor, and do not require discontinuation of treatment in most cases.

Despite the promising data on the efficacy and safety of colchicine for recurrent pericarditis that have accumulated in the past decade, large, controlled, prospective studies are required to provide definitive answers on the subject.

We thank Gloria Ginzach, Marian Propp, and Charlotte Sacks for their editorial and secretarial assistance.


Correspondence to Y. Adler, MD, Department of Cardiology, Rabin Medical Center, Beilinson Campus, Petah Tiqva, 49100, Israel.


  • 1Shabetai R. Diseases of the pericardium. In: Bennet JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: WB Saunders;1996:336–342.Google Scholar
  • 2Spodick DH. Diseases of the pericardium. In: Parmley WW, Chatterjee K, eds. Cardiology. Philadelphia, Pa: JB Lippincott; 1992;1–34.Google Scholar
  • 3Carmichael DB, Sprague HB, Wyman SM. Acute nonspecific pericarditis: clinical laboratory and follow-up considerations. Circulation.1951; 3:321–331.CrossrefMedlineGoogle Scholar
  • 4Clementy J, Jambert H, Dallarrhio M. Les pericarditis aigues recidivantes: 20 observations. Arch Mal Coeur.1979; 72:857–861.MedlineGoogle Scholar
  • 5Connolly DC, Burchell HB. Pericarditis: a ten-year survey. Am J Cardiol.1961; 7:7–14.CrossrefGoogle Scholar
  • 6Engle MA. Pericardiology and allied syndromes. In: Reddy PS, ed. Pericardial Disease. New York, NY: Raven Press; 1982:313–323.Google Scholar
  • 7Robinson J, Bergden W. Recurrent pericarditis. BMJ.1968; 2:272–275.CrossrefMedlineGoogle Scholar
  • 8Miller JI, Mansour KA, Hatcher CR. Pericardiectomy: current indications, concepts, and results in a university center. Ann Thorac Surg.1982; 84:40–45.Google Scholar
  • 9Spodick DH. The Pericardium: A Comprehensive Textbook. New York, NY: Marcel Dekker; 1997:422–432.Google Scholar
  • 10Adler Y, Zandman-Godard G, Ravid M, Avidan B, Zemer D, Ehrenfeld M, Shemesh J, Tomer Y, Shoenfeld Y. Usefulness of colchicine in preventing recurrences of pericarditis. Am J Cardiol.1994; 783:916–917.Google Scholar
  • 11Wright DG, Wolff SM, Fauci AS, Alling DW. Efficacy of intermittent colchicine therapy in familial Mediterranean fever. Ann Intern Med.1977; 86:162–165.CrossrefMedlineGoogle Scholar
  • 12Isselbacker KJ, Epstein A. Familial Mediterranean fever. In Fauci AS, Braunwald E, Isselbacker KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL, eds. Harrison’s Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:1644–1655.Google Scholar
  • 13Rodriguez de la Serna A, Guindo J, Marti V, Bayes de Luna A. Colchicine for recurrent pericarditis. Lancet.1987; 2:1517. Letter.Google Scholar
  • 14Guindo J, Rodriguez de la Serna A, Ramie J, de Miguel Diaz MA, Subirana MT, Perez Ayuso MJ, Cosin J, Bayes de Luna A. Recurrent pericarditis: relief with colchicine. Circulation.1990; 82:1117–1120.CrossrefMedlineGoogle Scholar
  • 15Millaire A, de Groote P, Decoulx E, Goullard L, Ducloux G. Treatment of recurrent pericarditis with colchicine. Eur Heart J.1994; 15:120–124.MedlineGoogle Scholar
  • 16Adler Y, Guindo J, Rodriguez de la Serna A, Shoenfeld Y, Ravid M, de Miguel M, Subirana M, Shemesh J, Finkelstein Y, Bayes T, Amir J, Zandman G, Martinez D, Langevitz P, Zemer D, Ehrenfeld M, Krivoy N, Sclarovsky B, Bayes de Luna A. Recurrent pericarditis and colchicine: 10 years of experience. J Am Coll Cardiol. 1997;29(suppl):24A. Abstract.Google Scholar
  • 17Froment R, Perrin A, Saint-Pierre A, Fleurette J. Efflorescence de péricardites idiopathiques récidivantes: rôle probable des antibiotiques et de la corticothérapie. J Med Lyon.1970; 51:113–114.MedlineGoogle Scholar
  • 18Godeau P, Derrida JP, Bletry O, Herreman G. Péricardites aigües récidivantes et cortico-dépendance. Sem Hôp Paris.1975; 51:2393–2400.MedlineGoogle Scholar
  • 19Tatibouet L, Olivier J, Germa D, Chuong van Hung. Les péricardites secondaires à un infarctus du myocarde. Sem Hôp Paris.1979; 55:1422–1426.MedlineGoogle Scholar
  • 20Clémenty J, Jambert H, Dallocchio M. Les péricardites aigües récidivantes. Arch Mal Coeur Vaiss.1979; 72:857–861.MedlineGoogle Scholar
  • 21Adolph RJ. Old drugs with new uses: colchicine for treatment of recurrent pericarditis. Circulation.1990; 82:1505–1506.CrossrefMedlineGoogle Scholar
  • 22Fowler NO, Harbin AD III. Recurrent acute pericarditis: follow-up study of 31 patients. J Am Coll Cardiol.1986; 7:300–305.CrossrefMedlineGoogle Scholar
  • 23Guindo J, Adler Y, Spodick DH, Rodriguez de la Serna A, Shoenfeld Y, Daniel-Riesco C, Finkelstein Y, Bayes-Genis A, Miguel de Miguel A, Subirana M, Sclarovsky S, Bayes de Luna A. Colchicine for recurrent pericarditis: 51 patients followed up for 10 years. Circulation. 1997;96(suppl I):1–29. Abstract.Google Scholar
  • 24Dinarello CA, Chusid MJ, Fauci AS, Callin JI, Dale DC, Wolf SM. Effect of prophylactic colchicine therapy on leukocyte function in patients with familial Mediterranean fever. Arthritis Rheum.1976; 19:618–622.CrossrefMedlineGoogle Scholar
  • 25Kershenebich D, Vargas F, Garcia Tsao G, Perez Tamayo R, Gent M, Rojkind M. Colchicine in the treatment of cirrhosis of the liver. N Engl J Med.1988; 318:1709–1713.CrossrefMedlineGoogle Scholar
  • 26Wahl SM, Wahl LM, McCarthy JB. Lymphocyte mediated activation of fibroblast proliferation and collagen production. J Immunol.1978; 121:942–946.MedlineGoogle Scholar
  • 27Ertel N, Omokoku B, Wallace S. Colchicine concentrations in leukocytes. Arthritis Rheum.1969; 12:293–298.Google Scholar
  • 28Millaire A, Durlaux G. Treatment of acute or recurrent pericarditis with colchicine. Circulation.1991; 83:1458–1459. Letter.Google Scholar
  • 29Adler Y, Guindo J, Finkelstein Y, Khouri A, Bayes Genis A. Colchicine for large pericardial effusions. Clin Cardiol.1998; 21:143–144.CrossrefMedlineGoogle Scholar
  • 30Famaey JP. Colchicine in therapy: state of the art and new perspectives of an old drug Clin Exp Rheumatol.1988; 6:305–317.MedlineGoogle Scholar

Heart-disease risk soars after COVID — even with a mild case

Authors: Saima May Sidik 10 February 2022


Massive study shows a long-term, substantial rise in risk of cardiovascular disease, including heart attack and stroke, after a SARS-CoV-2 infection.

Even a mild case of COVID-19 can increase a person’s risk of cardiovascular problems for at least a year after diagnosis, a new study1 shows. Researchers found that rates of many conditions, such as heart failure and stroke, were substantially higher in people who had recovered from COVID-19 than in similar people who hadn’t had the disease.

What’s more, the risk was elevated even for those who were under 65 years of age and lacked risk factors, such as obesity or diabetes.

“It doesn’t matter if you are young or old, it doesn’t matter if you smoked, or you didn’t,” says study co-author Ziyad Al-Aly at Washington University in St. Louis, Missouri, and the chief of research and development for the Veterans Affairs (VA) St. Louis Health Care System. “The risk was there.”

Al-Aly and his colleagues based their research on an extensive health-record database curated by the United States Department of Veterans Affairs. The researchers compared more than 150,000 veterans who survived for at least 30 days after contracting COVID-19 with two groups of uninfected people: a group of more than five million people who used the VA medical system during the pandemic, and a similarly sized group that used the system in 2017, before SARS-CoV-2 was circulating.

Troubled hearts

People who had recovered from COVID-19 showed stark increases in 20 cardiovascular problems over the year after infection. For example, they were 52% more likely to have had a stroke than the contemporary control group, meaning that, out of every 1,000 people studied, there were around 4 more people in the COVID-19 group than in the control group who experienced stroke.

The risk of heart failure increased by 72%, or around 12 more people in the COVID-19 group per 1,000 studied. Hospitalization increased the likelihood of future cardiovascular complications, but even people who avoided hospitalization were at higher risk for many conditions.

“I am actually surprised by these findings that cardiovascular complications of COVID can last so long,” Hossein Ardehali, a cardiologist at Northwestern University in Chicago, Illinois, wrote in an e-mail to Nature. Because severe disease increased the risk of complications much more than mild disease, Ardehali wrote, “it is important that those who are not vaccinated get their vaccine immediately”.COVID’s cardiac connection

Ardehali cautions that the study’s observational nature comes with some limitations. For example, people in the contemporary control group weren’t tested for COVID-19, so it’s possible that some of them actually had mild infections. And because the authors considered only VA patients — a group that’s predominantly white and male — their results might not translate to all populations.

Ardehali and Al-Aly agree that health-care providers around the world should be prepared to address an increase in cardiovascular conditions. But with high COVID-19 case counts still straining medical resources, Al-Aly worries that health authorities will delay preparing for the pandemic’s aftermath for too long. “We collectively dropped the ball on COVID,” he said. “And I feel we’re about to drop the ball on long COVID.”



  1. Xie, Y., Xu, E., Bowe, B. & Al-Aly, Z. Nature Med. (2022).PubMed Article Google Scholar 

Association of Myocarditis With BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children

Authors: Audrey Dionne, MD1,2Francesca Sperotto, MD1,2Stephanie Chamberlain1,2et alAnnette L. Baker, MSN, CPNP1,2Andrew J. Powell, MD1,2Ashwin Prakash, MD1,2Daniel A. Castellanos, MD1,2Susan F. Saleeb, MD1,2Sarah D. de Ferranti, MD, MPH1,2Jane W. Newburger, MD, MPH1,2Kevin G. Friedman, MD1,2

JAMA Cardiol. 2021;6(12):1446-1450. doi:10.1001/jamacardio.2021.347

Question  What are the findings on cardiac imaging in children with myocarditis after COVID-19 vaccination?

Findings  In this case series of 15 children who were hospitalized with myocarditis after receipt of the BNT162b2 messenger RNA COVID-19 vaccine for 1 to 5 days, boys were most often affected after the second vaccine dose, 3 patients had ventricular systolic dysfunction, and 12 patients had late gadolinium enhancement on cardiac magnetic resonance imaging. There was no mortality, and all but 1 patient had normal echocardiogram results on follow-up 1 to 13 days after discharge.

Meaning  COVID-19 vaccine-associated myocarditis may have a benign short-term course in children; however, the long-term risks remain unknown.Abstract

Importance  The BNT162b2 (Pfizer-BioNTech) messenger RNA COVID-19 vaccine was authorized on May 10, 2021, for emergency use in children aged 12 years and older. Initial reports showed that the vaccine was well tolerated without serious adverse events; however, cases of myocarditis have been reported since approval.

Objective  To review results of comprehensive cardiac imaging in children with myocarditis after COVID-19 vaccine.

Design, Setting, and Participants  This study was a case series of children younger than 19 years hospitalized with myocarditis within 30 days of BNT162b2 messenger RNA COVID-19 vaccine. The setting was a single-center pediatric referral facility, and admissions occurred between May 1 and July 15, 2021.

Main Outcomes and Measures  All patients underwent cardiac evaluation including an electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging.

Results  Fifteen patients (14 male patients [93%]; median age, 15 years [range, 12-18 years]) were hospitalized for management of myocarditis after receiving the BNT162b2 (Pfizer) vaccine. Symptoms started 1 to 6 days after receipt of the vaccine and included chest pain in 15 patients (100%), fever in 10 patients (67%), myalgia in 8 patients (53%), and headache in 6 patients (40%). Troponin levels were elevated in all patients at admission (median, 0.25 ng/mL [range, 0.08-3.15 ng/mL]) and peaked 0.1 to 2.3 days after admission. By echocardiographic examination, decreased left ventricular (LV) ejection fraction (EF) was present in 3 patients (20%), and abnormal global longitudinal or circumferential strain was present in 5 patients (33%). No patient had a pericardial effusion. Cardiac magnetic resonance imaging findings were consistent with myocarditis in 13 patients (87%) including late gadolinium enhancement in 12 patients (80%), regional hyperintensity on T2-weighted imaging in 2 patients (13%), elevated extracellular volume fraction in 3 patients (20%), and elevated LV global native T1 in 2 patients (20%). No patient required intensive care unit admission, and median hospital length of stay was 2 days (range 1-5). At follow-up 1 to 13 days after hospital discharge, 11 patients (73%) had resolution of symptoms. One patient (7%) had persistent borderline low LV systolic function on echocardiogram (EF 54%). Troponin levels remained mildly elevated in 3 patients (20%). One patient (7%) had nonsustained ventricular tachycardia on ambulatory monitor.

Conclusions and Relevance  In this small case series study, myocarditis was diagnosed in children after COVID-19 vaccination, most commonly in boys after the second dose. In this case series, in short-term follow-up, patients were mildly affected. The long-term risks associated with postvaccination myocarditis remain unknown. Larger studies with longer follow-up are needed to inform recommendations for COVID-19 vaccination in this population.Introduction

SARS-CoV-2 was first identified in China and evolved rapidly to a global pandemic. Vaccines to prevent SARS-CoV-2 infection are the current standard approach for curbing the pandemic. In the US, the BNT162b2 messenger RNA (mRNA) (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Janssen) vaccines were granted emergency use authorization for adults. On May 10, 2021, the emergency use authorization for the BNT162b2 vaccine was extended to children aged 12 years and older.1

Myocarditis has been reported as a rare complication of vaccination against other viruses.2 It was not reported in the initial messenger RNA COVID-19 vaccine trials, although the ability to detect rare events was limited by sample size. Since the emergency use authorization, myocarditis in adolescents and young adults after COVID-19 vaccine has been reported.35 In this series, we detail the occurrence of myocarditis after COVID-19 vaccination in an adolescent population, including comprehensive cardiac imaging evaluation and follow-up.MethodsPopulation

This case series included all patients younger than 19 years admitted at our center with acute myocarditis after COVID-19 vaccination. Myocarditis was defined as chest pain and an elevated troponin level in the absence of an alternative diagnosis. The institutional review board at Boston Children’s Hospital approved this study and granted an exemption from informed consent owing to use of deidentified data and the requirements of 45 CFR §46. This study followed the reporting guideline for case series.Data Collection and Definitions

Clinical data elements including demographic characteristics, laboratory values, and hospital course were collected from the electronic medical record. Patients’ race and ethnicity were self-reported by patients or parents according to the US Census categories6 and were collected because of their known association with COVID-19–related illnesses. Elevated troponin T level was defined as a troponin value greater than 0.01 ng/mL. Cardiac evaluation for all patients included electrocardiogram (ECG), echocardiogram, and cardiac magnetic resonance (CMR) imaging. Ventricular systolic dysfunction was defined as a left ventricular (LV) ejection fraction equal to or greater than 55% on echocardiogram or CMR results. Echocardiographic peak global longitudinal strain was measured from an apical 4-chamber view and peak global circumferential strain from a parasternal short-axis view at the midpapillary level using software (Tom Tec Image Arena, version 4.6; TOMTEC). Strain values were considered abnormal if the z score was less than or equal to −2 for age. Diastolic dysfunction was defined as a z score less than or equal to −2 for age, for septal e′ tissue Doppler, LV free wall e′, or the E/e′ ratio. CMR assessment included LV ejection fraction, T2-weighted myocardial imaging, LV global native T1, LV global T2, extracellular volume fraction, and late gadolinium enhancement (LGE).Statistical Analysis

Descriptive statistics were calculated for all study variables. Quantitative variables were summarized as median and range and categorical variables as frequencies and percentages.Results

Fifteen patients were admitted at the Department of Cardiology, Boston Children’s Hospital for management of myocarditis after COVID-19 vaccination between May 1 and July 15, 2021. The median age was 15 years (range, 12-18 years), and most patients were male (n = 14 [93%]). Patients self-identified as non-Hispanic White (n = 8 [53%]), Hispanic White (n = 2 [15%]), other Hispanic (n = 1 [8%]), other non-Hispanic (n = 1 [8%]), and unknown (n = 3 [20%]) (Table). All patients received the BNT162b2 mRNA vaccine. Symptoms occurred after the second dose of the vaccine in all but 1 case. No patients had a known prior COVID-19 infection, although 1 had reactive SARS-CoV-2 antibodies to the nucleocapsid protein.

Chest pain in 15 of 15 patients (100%) started at median 3 days (range, 1-6 days) after receiving the vaccine and lasted 1 to 9 days. Other symptoms included fever in 10 patients (67%), myalgia in 8 patients (53%), and headache in 6 patients (40%). Seven patients (47%) were treated with intravenous immunoglobulins (2 g/kg) and methylprednisolone (1 mg/kg/dose twice a day, transitioned to prednisone at time of discharge). Hospital length of stay was a median of 2 days (range, 1-5 days), and no patients required intensive care unit admission.Troponin

Troponin levels were elevated in all patients at admission (median, 0.25 ng/mL [range, 0.08-3.15 ng/mL]) and peaked 0.1 to 2.3 days after admission (Table). At the time of discharge, the troponin level had substantially decreased but remained elevated in all patients (Figure 1).Echocardiogram

On admission echocardiogram, 3 patients (20%) had global LV systolic ventricular dysfunction (EF 44%, 49%, and 53%), one of whom also had regional wall motion abnormality at the apex. Two patients (13%) with systolic dysfunction had abnormal diastolic function indices, and 1 patient (7%) with borderline EF (55%) had evidence of diastolic dysfunction. Five patients (33%) had abnormal global longitudinal or global circumferential strain (Figure 2; eFigure 1 and eTable in the Supplement). No patients had a coronary artery aneurysm or pericardial effusion.Electrocardiogram

The most frequent finding was diffuse ST-segment elevation consistent with pericarditis, present on admission in 6 patients (40%), and at some time during hospital admission in 8 patients (53%). Four additional patients had nonspecific ST segment changes. One patient (normal systolic and diastolic ventricular function; LGE on CMR) had nonsustained ventricular tachycardia during hospital admission. ST-T wave changes persisted at time of hospital discharge in 9 patients (69%). No patient had PR interval, QRS duration, or QTc duration prolongation.Cardiac Magnetic Resonance

CMR imaging was performed in all patients 1 to 7 days after the onset of symptoms. Systolic LV dysfunction was present in 3 patients (25%). Findings consistent with myocarditis were found in 13 patients (87%). LGE was present in 12 patients, and most often found in the inferolateral (n = 3) and anterolateral (n = 4) regions (eTable and eFigure 2 in the Supplement). The extracellular volume fraction was borderline elevated (28%-30%) in 4 patients (27%) and elevated (>30%) in 3 patients (25%). LV global native T1 was borderline elevated (1080-1100 milliseconds) in 2 patients and elevated (>1100 milliseconds) in 2 patients. Two patients had regional hyperintensity on T2-weighted imaging. LV global T2 was borderline elevated (56-60 milliseconds) in 1 patient.Follow-up

Follow-up information after hospital discharge was available for all patients (virtual visit in 1 patient; in-person with testing in 14 patients) and occurred 1 to 13 days after discharge. Four patients (27%) were asymptomatic with normal troponin level, ECG, and echocardiogram results.

Four patients (27%) had persistent symptoms, including fatigue in 3 patients (25%) and continued chest pain in 1 patient (7%). None of the patients with persistent symptoms had decreased EF at time of initial presentation (1 with abnormal strain) and 3 patients (75%) had abnormal CMR results with LGE.

One asymptomatic patient (7%) had persistent borderline low LV EF (54%), reduced circumferential strain (z score, −2.3), and reduced lateral e′ velocity (z score, −2.8) measured by echocardiogram at 8 days after discharge; all other patients had normal echocardiogram results. Ventricular systolic function recovered (EF>55%) in 2 to 11 days (Figure 1).

ECG changes persisted in 4 patients (33%) and included nonspecific ST-T wave changes in 4 patients (33%) or new T-wave inversion in 3 patients (20%). One patient (7%) with nonsustained ventricular tachycardia during hospital admission had recurrence of nonsustained ventricular tachycardia on 6 days of ambulatory ECG monitoring, despite initiation of β-blocker therapy.

Troponin levels remained mildly elevated at follow-up in 3 patients (20%) (Figure 1). One patient (7%) with a persistently elevated troponin level (0.05 ng/mL) had continuing fatigue. All patients with persistently elevated troponin levels had had prior abnormalities on CMR (2 patients with LGE, 1 patient with elevated extracellular volume fraction).Discussion

In this early experience of 15 cases, myocarditis typically occurred in male patients after the second dose of the COVID-19 vaccine. All patients in this series had a benign course; none required intensive care unit admission and all were discharged alive from the hospital within 5 days. LV systolic function at presentation was normal in most patients and normalized within a few days in all but 1 patient who had persistent borderline low LV function. This finding differs from other forms of myocarditis in which LV systolic dysfunction and arrhythmias are more common, with 50% of children requiring intensive care unit admission, a mean hospital length of stay of 14.4 days, and a mortality rate of 7.8%.79

Although vaccine-associated cases of myocarditis to date have had uncomplicated short-term course, the long-term prognosis remains unclear. Of note, CMR LGE was a frequent finding at time of diagnosis. In this clinical setting, LGE reflects an increased volume of distribution of the gadolinium-based contrast agent in the affected region likely related to myocyte necrosis and/or extracellular edema. In nonvaccine-associated myocarditis, the presence of LGE is associated with increased risk for adverse cardiovascular events during follow-up.1012 Thus, longitudinal studies of patients with myocarditis after COVID-19 vaccine will be important to better understand long-term risks.

To date, there have been 1226 reports of myocarditis after messenger RNA vaccination to the Vaccine Adverse Event Reporting System (VAERS), including 687 in persons aged less than 30 years.13 Crude reporting rates using vaccine administration data estimates the highest rate among male individuals aged 12 to 17 years (62.8 cases per million), similar to our observations. Despite the risks of myocarditis associated with vaccination, the benefits of vaccination likely outweigh risks in children and adolescents. It is estimated that COVID-19 vaccination in males aged 12 to 29 years can prevent 11 000 COVID-19 cases, 560 hospitalizations, 138 intensive care unit admissions, and 6 deaths compared with 39 to 47 expected myocarditis cases.Limitations

This study has limitations. Limitations to this series include the lack of COVID-19 vaccine administration data, which does not permit calculation of incidence or identification of risk factors for myocarditis. Mild cases may have been missed due to the novelty of this complication and the lack of routine screening.Conclusions

Myocarditis may be a rare complication after COVID-19 vaccination in patients aged less than 19 years. In this case series study, the short-term clinical course was mild in most patients; however, the long-term risks remain unknown. Risks and benefits of COVID-19 vaccination must be considered to guide recommendations for vaccination in this population.Back to topArticle Information

Accepted for Publication: July 20, 2021.

Published Online: August 10, 2021. doi:10.1001/jamacardio.2021.3471