A recent autopsy study examined 74 post‑mortem heart samples from patients who had recovered from COVID‑19 at least 60 days prior. Researchers used the NanoString nCounter® Coronavirus Panel Plus to detect reverse‑strand SARS‑CoV‑2 RNA, a marker of active viral replication, in left‑ventricular tissue. The assay identified viral replication in 11 cases (15%).

Among the 11 V+ hearts, 82% exhibited clinical long‑COVID symptoms, compared to 37% in the 63 V‑ group (p=0.0075). V+ hearts showed a higher heart‑weight‑to‑LV‑wall‑thickness ratio (437 g/cm vs 340 g/cm, p=0.005), increased LV dilatation (64% vs 24%, p=0.01), and more pericardial effusion ≥30 mL (40% vs 14%, p=0.048). In situ hybridization confirmed viral spike gene presence in myocytes, and immunohistochemistry revealed elevated IRF4 expression in epicardial cells.

Differential gene‑expression analysis uncovered 44 genes linked to inflammation and interferon signaling, implicating IRF4 as a central mediator of the observed myocardial remodeling. These findings provide molecular evidence that residual viral replication may drive the structural and immune changes underlying long‑COVID cardiac symptoms, suggesting new diagnostic markers and therapeutic targets.

The study highlights the utility of transcriptomic panels and in‑situ assays for post‑mortem viral surveillance, offering a framework for future investigations into chronic viral persistence in organ systems.