Better clinical outcomes in COVID-19 and vaccine-related myocarditis than classic myocarditis in children

Myocarditis is a condition that can lead to strokes or heart attacks. It is normally caused by infection with a virus, but it can be a reaction to a drug or inflammatory disease. In myocarditis, the myocardium becomes inflamed, reducing the heart’s ability to pump blood and causing arrhythmias. Symptoms include chest pain, fluid build-up, and swelling of the lower body.

Study: Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children. Image Credit: Kateryna Kon / Shutterstock

Coronavirus disease 2019 (COVID-19) has been known to cause a multisystem inflammatory syndrome in children (MIS-C), which has caused the rates of myocarditis to rise significantly. More recently, studies have also begun to show evidence suggesting that some of the mRNA-based COVID-19 vaccines may lead to myocardial injury and myocarditis.

Researchers from the Emory University School Of Medicine have investigated the differences between ‘classic’ myocarditis, COVID-19 induced myocarditis (MIS-C myocarditis), and vaccine-related myocarditis.

A preprint version of the study is available on the medRxiv* server while the article undergoes peer review.

The study

The researchers gathered data from individuals below 21 years of age from between 2015-2019 for classic myocarditis, patients between March 2020 and February 2021 who met the CDC definition for MIS-C myocarditis, and patients between May and June 2021 who had presented with myocarditis following vaccine administration, with no alternative cause for vaccine-related myocarditis.

They primarily examined left ventricular ejection fraction (LVEF), peak troponin I and brain natriuretic peptide (BNP) levels, and treatment undergone. They also gathered information on symptoms presented, electrocardiographic (ECG) findings, and evidence of anemia, thrombocytopenia, and lymphopenia.

The scientists gathered the data of over 200 patients, 43 of which presented with classic myocarditis, nine with vaccine-related myocarditis, and the rest with the MIS-C variant.

Generally, MIS-C myocarditis affected younger patients compared to the other two variants, and men were more affected than women. Classic myocarditis and MIS-C predominantly affected African Americans, while vaccine-related myocarditis was more likely to affect White individuals.

However, with such a small sample size, and several studies revealing higher vaccination rates amongst White Americans, it is difficult to determine the cause of this bias.

MIS-C myocarditis patients were significantly less likely to present with chest pain than the other two variants. Troponin was highest in the classic myocarditis group, while BNP was higher in MIS-C patients, who showed the most obvious hematologic derangements such as lymphopenia, leukocytosis, and thrombocytopenia.

There were also significant differences between classic and vaccine-related myocarditis and MIS-C myocarditis in ECG anomalies, with MIS-C myocarditis showing significantly lower incidence. Classic myocarditis showed the lowest results for LVEF, followed by MIS-C and then vaccine-related myocarditis.

There was one death and one heart transplant among the classic myocarditis group, with the rest of the patients being discharged. 44% of classic myocarditis patients required medication to prevent heart failure, while only 3% of the MIS-C patients did, and none of the vaccine-related myocarditis patients. Vaccine-related myocarditis recovered completely within three days of hospitalization, along with 76% of MIS-C patients but only 47% of classic myocarditis patients.


The authors highlight the far milder course of vaccine-related myocarditis than the other two forms, with significantly higher recovery rates, lower likelihood of cardiac dysfunction, and much lower incidence overall. MIS-C myocarditis also showed a more optimistic prognosis than classic myocarditis, with a greater likelihood of full and fast recovery.

One key finding was the level of ventricular recovery seen in MIS-C myocarditis patients with even severely depressed cardiac function. While in classic cases, patients showing similar levels of dysfunction would progress to heart transplant or death, almost all patients with MIS-C myocarditis regained normal cardiac function within days and showed full recovery by three months.

The authors suggest that this is likely due to the difference between the cause of the inflammation. Once the systemic inflammation associated with MIS-C is resolved, the heart can heal. However, in classic myocarditis, resolving the inflammation can be much trickier, as there may be immune mediation due to viral infection and myocyte injury.

Aside from this, they suggest that the differences between chest pain seen in MIS-C and classic myocarditis may be due to the respective age of the patients – the younger MIS-C patients may have more trouble expressing the specific discomfort they are feeling.

These findings are important for healthcare professionals treating various forms of myocarditis and for providing important information into the impact of COVID-19 infection and vaccination.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behaviour, or treated as established information

Journal reference:

Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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