Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries

Area of Science:

• Cardiovascular Biology
• Infectious Diseases
• 3D Organoid Technology

Background:

• Acute cardiac injuries affect 20-25% of hospitalized COVID-19 patients, necessitating better research models.
• Current research lacks 3D organotypic models for studying COVID-19 cardiac pathology and drug efficacy.

Approach:

• Human cardiac organoids (hCOs) were stimulated with Interleukin-1 beta (IL-1β), a key COVID-19 cytokine, to simulate hyperinflammation.
• IL-1β stimulation induced a cytokine profile mirroring the COVID-19 cytokine storm in hCOs.
• Transcriptomic, structural, and functional changes in stimulated hCOs were analyzed.

Key Points:

• IL-1β-stimulated hCOs recapitulated key features of COVID-19 cardiac injury, including transcriptomic and structural alterations.
• Comparison with COVID-19 autopsy tissues highlighted hyper-inflammation's role and the endothelium's cardioprotective potential.
• The model demonstrated potential for assessing immunomodulatory drugs and COVID-19 cardiac injury reversibility under various conditions.

Conclusions:

• Human cardiac organoids provide a viable 3D platform for modeling COVID-19-induced cardiac injuries and hyperinflammation.
• This model system facilitates mechanistic studies, drug screening, and evaluation of therapeutic interventions for COVID-19 cardiac complications.