Researchers Uncover How SARS-CoV-2 Inflicts Damage on Heart Cells
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As the COVID-19 pandemic unfolded, it became clear that the effects of the disease were more widespread than just the respiratory system, with damage to the heart and other organs seen in many patients. In some cases, damage may be long term, so it is important to understand how it occurs and develop ways to reduce or prevent it.
In a recent preprint study,* a team of researchers from Gladstone Institutes discovered new insights into how SARS-CoV-2 causes heart damage. Using a cardiac disease model, the authors found that the virus infected cardiomyocytes, causing structural abnormalities including severely fragmented sarcomeres and missing nuclear DNA. The model could also be used to help the development of drugs to prevent or treat these effects.
To learn more about the findings and their implications for the monitoring and treatment of COVID-19 patients, we spoke to Bruce Conklin, MD, senior investigator at Gladstone Institutes.
Anna MacDonald (AM): Can you give us an overview of what your findings show about SARS-CoV-2 infection and cardiac damage?
Bruce Conklin (BC): COVID-19 was initially identified as a respiratory disease, but scientists now appreciate that it also affects several other organs in the body, including the heart. Heart damage is a major determinant of COVID-19 related deaths, and even patients who experience only mild COVID-19 symptoms exhibit signs of cardiac dysfunction several months after recovery.
This new study helps explain how SARS-CoV-2, the virus that causes COVID-19, inflicts damage on heart cells. Our findings show the virus’s unexpected effects on the structure of heart cells in the lab, as well as in heart tissue from COVID-19 patients.
AM: Evidence of the structural abnormalities in the cardiomyocytes was seen in patients who had not been diagnosed with COVID-19 related heart disease. What implications does this have for the monitoring and treatment of COVID-19 patients?
BC: We only have samples from autopsies, where we do have findings consistent with the same type of damage in heart cells. In living patients, there are blood tests (troponin) that indicate that many patients have injured heart cells, but currently there is no cardiac-specific treatment for these patients. We hope that by understanding this problem more, it could lead to new types of treatment.
AM: Could direct myocardial infection be involved in the development of cardiac damage seen in sufferers of multisystem inflammatory syndrome in children?
BC: Yes, it could certainly play a role in this form of disease.
Laura Lansdowne (LL): In your preprint you mention that although cell-based drug screens exist for many pathogens, including SARS-CoV-2, the unique cytoarchitecture of cardiomyocytes and the specific impact of the virus on myocytes presents new screening possibilities. Could you elaborate on this?
BC: Cardiomyocytes have specific structures called sarcomeres that can be observed with microscope. Since the sarcomeres lose structure is a specific way with SARS-CoV-2, the sarcomeres are like a molecular thermometer that can tell us that a virus is in the cardiomyocytes, and or if a drug is preventing damage from the virus.
LL: Could you comment on the importance of physiological relevance when testing therapeutics in in vitro cell-based screening systems? How have advances in cell culture technologies enabled scientists to better imitate the in vivo environment?
BC: Using the iPSC-derived cardiomyocytes could screen thousands of drugs, which would be impossible in people or animal models.
AM: What further work do you have planned?
BC: We hope to set up screens for drugs that will prevent or repair cardiac damage. In addition, we hope to understand the molecular mechanisms by which the SARS-CoV-2 virus causes cardiac damage.
Bruce Conklin was speaking to Anna MacDonald and Laura Lansdowne, Science Writers for Technology Networks.
*This article is based on research findings that are yet to be peer-reviewed. Results are therefore regarded as preliminary and should be interpreted as such. Find out about the role of the peer review process in research here. For further information, please contact the cited source.
