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

Arhontoulis, D. C.; Kerr, C.; Richards, D.; Tjen, K.; Hyams, N.; Jones, J. A.; Deleon-Pennell, K.; Menick, D. R.; Lindner, D.; Westermann, D.; Mei, Y.

doi:10.1101/2022.01.31.478497

bioRxiv · 10.1101/2022.01.31.478497

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

Arhontoulis, D. C.·Kerr, C.·Richards, D.·Tjen, K.·Hyams, N.·Jones, J. A.·Deleon-Pennell, K.·Menick, D. R.·Lindner, D.·Westermann, D.·Mei, Y.

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Abstract

Acute cardiac injuries occur in 20-25% of hospitalized COVID-19 patients. Despite urgent needs, there is a lack of 3D organotypic models of COVID-19 hearts for mechanistic studies and drug testing. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac injuries caused by COVID-19 hyperinflammation. As IL-1{beta}is an upstream cytokine and a core COVID-19 signature cytokine, it was used to stimulate hCOs to induce the release of a milieu of proinflammatory cytokines that mirror the profile of COVID-19 cytokine storm. The IL-1 {beta} treated hCOs recapitulated transcriptomic, structural, and functional signatures of COVID-19 hearts. The comparison of IL-1{beta} treated hCOs with cardiac tissue from COVID-19 autopsies illustrated the critical roles of hyper-inflammation in COVID-19 cardiac insults and indicated the cardioprotective effects of endothelium. The IL-1{beta} treated hCOs also provide a viable model to assess the efficacy and potential side effects of immunomodulatory drugs, as well as the reversibility of COVID-19 cardiac injuries at baseline and simulated exercise conditions.

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Arhontoulis, D. C., Kerr, C., Richards, D., Tjen, K., Hyams, N., Jones, J. A., Deleon-Pennell, K., Menick, D. R., Lindner, D., Westermann, D., Mei, Y.. 2022-02-01. Human Cardiac Organoids to Model COVID-19 Cytokine Storm Induced Cardiac Injuries. https://doi.org/10.1101/2022.01.31.478497

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