In-Depth Evaluation of a Case of Presumed Myocarditis After the Second Dose of COVID-19 mRNA Vaccine

Abstract

Supplemental Digital Content is available in the text.

Keywords: COVID-19; COVID-19 vaccine; myocarditis; vaccine.

Figure 1.

ECG and coronary angiogram. A, The ECG on presentation to the emergency department. B, A posterior anterior cranial projection of a dominant right coronary artery and with no severe angiographic stenoses or flow-limiting lesions in the main vessel or its branches. C, A right anterior oblique caudal projection of a bifurcating left coronary artery and no severe angiographic stenoses or flow-limiting lesions in the main vessel or its branches.

Figure 2.

Phase-sensitive inversion-recovery cardiac magnetic resonance imaging. Right, Short-axis views demonstrating linear and curvilinear delayed enhancement in the subepicardial inferior basal and mesocardial midventricular region, compatible with nonischemic pattern of delayed enhancement. Middle, A native T1 map showing globally increased T1 values (1054 ms), Local native myocardial T1 (short axis [SA] and 4 chamber [4CH] midwall) (965 ± 35) and specifically higher values in the regions of delayed enhancement. The color map shows relaxation times with normal relaxation time in green and increased relaxation time in red and orange. Left, Native T2 map with heterogenous relative increased T2 values within the same segments (arrows) (maximum T2 value was 65 ms) (local normal T2 values for our institution, 45–64 ms). Color scale shows time in milliseconds.

Figure 3.

Antibody profile to viral antigens in the case of interest as compared with naive vaccinated, naive unvaccinated, and COVID-19 unvaccinated patients. The heatmap shows immunoglobulin G reactivity expressed in terms of row z-score for a respective antigen across different patient samples. Each antigen is organized into rows color-coded by virus, for serum specimens organized into columns classified as naive unvaccinated (N_UV, 8 samples), (COV_UV, 10 samples), naive vaccinated (N_V, 10 samples), naive Moderna vaccinated controls (N_M, 2 samples), and case of interest samples (CI_S, collections at day 1, day 2, day 3, and day 4 after symptom onset: S1, S2, S3, and S4 in the respective order). Reactivity is represented by color (light blue=low, black=mid, ellow=high). The heatmap has normalized row z-score values, a typical scaling method that helps better visualization of analytes with varying trends in the expression/reactivity between samples. Although a normalized row z-score can better represent the nonrandomness of directionality within a dataset, a negative z-score does not indicate a complete absence of expression/reactivity. A negative z-score means comparatively a lower raw scores/absolute expression. CMV indicates cytomegalovirus; COVID-19, coronavirus disease 2019; EBV, Epstein-Barr virus; and RSV, respiratory syncytial virus.

Figure 4.

SARS-CoV-2–related antibody status in the case of interest as compared with naive vaccinated, naive unvaccinated, and COVID-19–unvaccinated patients. Comparison of SARS-CoV2–related antibody response in the case of interest with naive vaccinated, naive unvaccinated, and COVID unvaccinated patients. A, Evaluation of spike-specific IgG antibody response. B, Comparison of spike-specific IgM levels. C, Comparison of nucleocapsid-specific antibody response. For A through C, all the patient samples in the N_V group were immunized with Pfizer vaccine. AU indicates arbitrary units; CI_S2, case of interest sampled at day 2 after symptom onset; CI_S4, case of interest sampled at day 4 after symptom onset; COVID-19, coronavirus disease 2019; COV_UV, COVID-19 unvaccinated; Ig, immunoglobulin; N_M, age- and vaccine (Moderna)–matched naive (positive controls for case of interest); N_UV, naive unvaccinated; N_V, naive vaccinated; SARS-CoV2, severe acute respiratory syndrome coronavirus 2; and SP, spike. Dashed brown line indicates the manufacturer-recommended positive threshold of the respective antibody assays used.

Figure 5.

Cytokine profile in the case of interest as compared with naive vaccinated, naive unvaccinated, and COVID-19–unvaccinated patients. The heatmap shows reactivity expressed in terms of row z-score for a respective antigen across different patient samples. Each row in the graphics represent a cytokine for serum specimens organized into columns classified as naive unvaccinated (N_UV, 8 samples), COVID-19 unvaccinated (COV_UV, 10 samples), naive vaccinated (N_V, 10 samples), naive Moderna vaccinated controls (N_M, 2 samples), and case of interest samples (CI_S, 4 different collection days at day 1, day 2, day 3, and day 4 after symptom onset: S1, S2, S3, and S4 in the respective order). The reactivity intensity ranges from turquoise (low) to black (moderate) or yellow (high). For the groups N_M and CI_S, each patient sample was run in duplicates that were averaged and represented. Some of the samples that displayed values below the least detection range were arbitrarily assigned a lowest value. COVID-19 indicates coronavirus disease 2019.

Figure 6.

Antibody profiles to self-antigens in the case patient relative to unvaccinated naive and COVID-19 patient samples. The heatmap shows the Phenolyzer-prioritized candidate proteins involved in cardiac disease expressed in terms of mean of the individual signal intensities from the duplicate samples that were corrected for background intensity followed by variance stabilizing normalization (VSN). Each row in the graphics represent the analytes for serum specimens organized into columns classified as naive unvaccinated (N_UV, 2 samples), COVID-19 unvaccinated (COV_UV, 1 sample) and case of interest samples (CI_S; day 1 sample after symptom onset). The reactivity intensity ranges from blue (low) to white (moderate) or red (high). Horizontal black lines segregate the subpanel cluster where autoantibodies are altered either commonly in both COV_UV and CI_S or only in COV^UV or CI_S relative to N_UV. A, IgM-specific autoantibody changes. B, IgG-specific autoantibody changes. Abs indicates antibodies; COVID-19, coronavirus disease 2019; and Ig, immunoglobulin.