# Evidence for Autoimmunity in the Pathogenesis of COVID-19-Induced Myocarditis

## TL;DR

This study shows that immune responses to SARS-CoV-2 may lead to heart inflammation in some patients with COVID-19.

## Contribution

The study provides evidence that autoimmunity may play a role in the development of myocarditis following SARS-CoV-2 infection.

## Key findings

- PBMCs from the patient showed proliferation in response to SARS-CoV-2 spike protein and myocardial tissue extract.
- Patient PBMCs secreted higher IFN-γ compared to healthy controls.
- Passive transfer of patient PBMCs or IgG increased cardiac IFN-γ transcript levels in mice.

## Abstract

Myocarditis has been described following SARS-CoV-2 infection. The mechanisms underlying COVID-19-associated myocarditis remain incompletely understood. Peripheral blood mononuclear cells (PBMCs), IgG fractions, and myocardial biopsy tissue were obtained from a patient with COVID-19 myocarditis. Cellular responses to SARS-CoV-2 spike protein and myocardial tissue extract were assessed in vitro. PBMCs and purified IgG were passively transferred into Rag2/IL2RG-/- mice. Interferon-gamma (IFN-γ) production and cardiac IFN-γ transcript levels were measured. PBMCs from the myocarditis patient proliferated in response to spike protein and myocardial tissue extract, whereas PBMCs from a healthy control did not. PBMCs from the patient secreted higher concentrations of IFN-γ compared with the healthy control. Introduction of patient PBMCs or IgG into Rag2/IL2RG-/- mice resulted in higher cardiac IFN-γ transcript levels compared with control PBMCs or IgG. These findings demonstrate cellular reactivity to SARS-CoV-2 spike protein and myocardial tissue, increased IFN-γ production, and induction of cardiac IFN-γ expression following passive transfer of immune components.