Background: Myocarditis, diagnosed by symptoms and troponin elevation, has been well-described with COVID-19 infection, as well as shortly after COVID-19 vaccination. The literature has characterized the outcomes of myocarditis following COVID-19 infection and vaccination, but clinicopathologic, hemodynamic, and pathologic features following fulminant myocarditis have not been well-characterized. We aimed to compare clinical and pathological features of fulminant myocarditis requiring hemodynamic support with vasopressors/inotropes and mechanical circulatory support (MCS), in these two conditions. Methods: We analyzed the literature on fulminant myocarditis and cardiogenic shock associated with COVID-19 and COVID-19 vaccination and systematically reviewed all cases and case series where individual patient data were presented. We searched PubMed, EMBASE, and Google Scholar for “COVID”, “COVID-19”, and “coronavirus” in combination with “vaccine”, “fulminant myocarditis”, “acute heart failure”, and “cardiogenic shock”. The Student’s t-test was used for continuous variables and the χ2 statistic was used for categorical variables. For non-normal data distributions, the Wilcoxon Rank Sum Test was used for statistical comparisons. Results: We identified 73 cases and 27 cases of fulminant myocarditis associated with COVID-19 infection (COVID-19 FM) and COVID-19 vaccination (COVID-19 vaccine FM), respectively. Fever, shortness of breath, and chest pain were common presentations, but shortness of breath and pulmonary infiltrates were more often present in COVID-19 FM. Tachycardia, hypotension, leukocytosis, and lactic acidosis were seen in both cohorts, but patients with COVID-19 FM were more tachycardic and hypotensive. Histologically, lymphocytic myocarditis dominated both subsets, with some cases of eosinophilic myocarditis in both cohorts. Cellular necrosis was seen in 44.0% and 47.8% of COVID-19 FM and COVID-19 vaccine FM, respectively. Vasopressors and inotropes were used in 69.9% of COVID-19 FM and in 63.0% of the COVID-19 vaccine FM. Cardiac arrest was observed more in COVID-19 FM (p = 0.008). Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiogenic shock was also used more commonly in the COVID-19 fulminant myocarditis group (p = 0.0293). Reported mortality was similar (27.7%) and 27.8%, respectively) but was likely worse for COVID-19 FM as the outcome was still unknown in 11% of cases. Conclusions: In the first series to retrospectively assess fulminant myocarditis associated with COVID-19 infection versus COVID-19 vaccination, we found that both conditions had a similarly high mortality rate, while COVID-19 FM had a more malignant course with more symptoms on presentation, more profound hemodynamic decompensation (higher heart rate, lower blood pressure), more cardiac arrests, and higher temporary MCS requirements including VA-ECMO. In terms of pathology, there was no difference in most biopsies/autopsies that demonstrated lymphocytic infiltrates and some eosinophilic or mixed infiltrates. There was no predominance of young males in COVID-19 vaccine FM cases, with male patients representing only 40.9% of the cohort.
