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Types of Myocarditis Related to COVID-19
Quick Takes
- This study identified two subsets of patients with fulminant COVID-19–related myocarditis with different clinical/biological presentations, outcomes, and immunological profiles.
- Those with MIS-A criteria more often have elevated serum levels of IL-17 and IL-22, while those without are frequently positive for serum RNA polymerase III autoantibodies, have high serum level of IFN-α, and more often require ECMO.
- MIS-A- cases, owing to the high risk of refractory cardiogenic shock, should be urgently referred to a center with VA-ECMO capability.
Study Questions:
What are the characteristics and clinical outcome between patients with fulminant COVID-19–related myocarditis fulfilling multisystem inflammatory syndrome (MIS)-A criteria (MIS-A+) or not (MIS-A-)?
Methods:
The investigators conducted a monocentric retrospective analysis of consecutive fulminant COVID-19–related myocarditis in a 26-bed intensive care unit (ICU). Serum concentrations of interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. Cumulative probabilities of survival were calculated using the Kaplan-Meier method and compared with log-rank tests.
Results:
Between March 2020–June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19–related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation (VA-ECMO) 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A- patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptom onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with VA-ECMO (92% vs. 16%; p < 0.0001). In-hospital mortality was higher in MIS-A- patients (31% vs. 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and TNF-α, whereas MIS-A- had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A- patients (54%) but in none of the MIS-A+ patients.
Conclusions:
The authors reported that MIS-A+ and MIS-A- fulminant COVID-19–related myocarditis patients have two distinct phenotypes with different clinical presentations, prognosis, and immunological profiles.
Perspective:
This study identified two subsets of patients with fulminant COVID-19–related myocarditis with very different clinical/biological presentations, outcomes, and immunological profiles. Those with MIS-A criteria more often have elevated serum levels of IL-17 and IL-22, while those without are frequently positive for serum RNA polymerase III autoantibodies, have a high serum level of IFN-α and more often require ECMO, and differentiating these patient subtypes seems relevant for their management. Of note, MIS-A- cases, owing to the high risk of refractory cardiogenic shock, should be urgently referred to a center with VA-ECMO capability and closely monitored to avoid a too-late cannulation known to be associated with poor outcome. Additional studies are also indicated to characterize the role of RNA polymerase III antibodies in the pathophysiology of MIS-A COVID-19–related fulminant myocarditis.
Clinical Topics: Cardiovascular Care Team, COVID-19 Hub, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure
Keywords: COVID-19, Cytokines, Dobutamine, Extracorporeal Membrane Oxygenation, Heart Failure, Hospital Mortality, Inflammation Mediators, Intensive Care Units, Interferons, Interleukins, Receptors, Interleukin, Myocarditis, Norepinephrine, Phenotype, Secondary Prevention, Renal Replacement Therapy, Respiration, Artificial, RNA, Shock, Cardiogenic, Stroke Volume, Tumor Necrosis Factors, Ventricular Function, Left
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