Fig. 1: Distinct cellular and molecular signatures in Non-COVID-19, Post-COVID-19 and Post-Vaccination inflammatory cardiomyopathies.

a, Infographic depicting metadata for Non-COVID-19 (n = 8), Post-COVID-19 (n = 10), Post-Vaccination (n = 4) and MIS-C (n = 2) patients. Left panel, patient age; women and men, light and dark gray, respectively. Middle panels, box plots showing serum levels of troponin T, NT-pro-BNP and CRP; dashed lines and blue areas indicate normal ranges. Right panel, box plots showing left ventricular ejection fraction (EF). b, snRNA-seq workflow schematic: EMBs were lysed and nuclei purified using FACS. Nuclei were processed using 10x Chromium 3′ chemistry. Image shows EMB size before nuclei isolation. c, UMAP embedding of 205,596 nuclei delineated 10 cardiac cell types and unassigned populations (gray). d, Upper panel, mean cell type abundances (%) in controls (n = 18). Lower panel, proportional changes of cell types in Non-COVID-19 (n = 8), Post-COVID-19 (n = 10) and Post-Vaccination (n = 4) versus control. Color scale: red (increase) and blue (decrease). Significant P values (FDR ≤ 0.05) are shown. P values were calculated with the two-sided t-test based on CLR-transformed values with Benjamini–Hochberg correction. MIS-C significance was not calculated due to low sample size (n = 2). e, Proportions of myeloid and lymphoid cells in control (n = 18) and MIS-C (n = 2) groups as well as in a follow-up biopsy from one patient with MIS-C.The patient with MIS-C with pre-treatment and post-treatment EMBs is indicated by a dashed line. Significance was not calculated due to low sample size (n = 2). f, Box plots as described in a showing snRNA-seq pseudo-bulk expression levels of cytokines in cardiac tissue from patient and control groups (control: n = 18, Non-COVID-19: n = 8, Post-COVID-19: n = 10, Post-Vaccination: n = 4). Significant P values (FDR ≤ 0.05) are shown. P values were calculated using the quasi-likelihood F-test with Benjamini–Hochberg correction. g, Pie charts comparing cell type resolved absolute mean expression levels of IL16 and IL18 between conditions. Pie size reflects absolute detection levels; colors indicate relative cell type contribution. h, Dot plots showing differential expression of IFNγ response genes in patient groups relative to controls in major cardiac cell types. Dot colors indicate log2-transformed FCs (log2FCs). Dot sizes indicate absolute log2FC. Black circles indicate significance (FDR ≤ 0.05). P value calculations are as in f. Box plots in a, e and f: boxes show interquartile range (IQR); vertical bars indicate the median; and whiskers extend from minimum to maximum values. Dots show individual measurements per patient. Adipo, adipocyte; Lymph, lymphoid; Myel, myeloid.