COVID-19: Study shows virus can infect heart cells in lab dish
Research uses stem cell technology to learn how coronavirus may directly attack heart muscle

Date:
June 30, 2020
Source:
Cedars-Sinai Medical Center
Summary:
A new study shows that SARS-CoV-2, the virus that causes COVID-19
(coronavirus), can infect heart cells in a lab dish, indicating
it may be possible for heart cells in COVID-19 patients to be
directly infected by the virus.



FULL STORY ==========================================================================
A new study shows that SARS-CoV-2, the virus that causes COVID-19 (coronavirus), can infect heart cells in a lab dish, indicating it may
be possible for heart cells in COVID-19 patients to be directly infected
by the virus. The discovery, published today in the journal Cell Reports Medicine, was made using heart muscle cells that were produced by stem
cell technology.


========================================================================== Although many COVID-19 patients experience heart problems, the reasons
are not entirely clear. Pre-existing cardiac conditions or inflammation
and oxygen deprivation that result from the infection have all been
implicated. But until now, there has been only limited evidence that
the SARS-CoV-2 virus directly infects the individual muscle cells of
the heart.

"We not only uncovered that these stem cell-derived heart cells are
susceptible to infection by novel coronavirus, but that the virus
can also quickly divide within the heart muscle cells," said Arun
Sharma, PhD, a research fellow at the Cedars-Sinai Board of Governors Regenerative Medicine Institute and first and co-corresponding author
of the study. "Even more significant, the infected heart cells showed
changes in their ability to beat after 72 hours of infection." The study
also demonstrated that human stem cell-derived heart cells infected
by SARS-CoV-2 change their gene expression profile, further confirming
that the cells can be actively infected by the virus and activate innate cellular "defense mechanisms" in an effort to help clear out the virus.

While these findings are not a perfect replicate of what is happening
in the human body, this knowledge may help investigators use stem
cell-derived heart cells as a screening platform to identify new antiviral compounds that could alleviate viral infection of the heart, according
to senior and co- corresponding author Clive Svendsen, PhD.

"This viral pandemic is predominately defined by respiratory symptoms,
but there are also cardiac complications, including arrhythmias,
heart failure and viral myocarditis," said Svendsen, director of the Regenerative Medicine Institute and professor of Biomedical Sciences
and Medicine. "While this could be the result of massive inflammation
in response to the virus, our data suggest that the heart could also be directly affected by the virus in COVID- 19." Researchers also found that treatment with an ACE2 antibody was able to blunt viral replication on
stem cell-derived heart cells, suggesting that the ACE2 receptor could
be used by SARS-CoV-2 to enter human heart muscle cells.

"By blocking the ACE2 protein with an antibody, the virus is not as easily
able to bind to the ACE2 protein, and thus cannot easily enter the cell,"
said Sharma. "This not only helps us understand the mechanisms of how
this virus functions, but also suggests therapeutic approaches that could
be used as a potential treatment for SARS-CoV-2 infection." The study
used human induced pluripotent stem cells (iPSCs), a type of stem cell
that is created in the lab from a person's blood or skin cells. IPSCs
can make any cell type found in the body, each one carrying the DNA of
the individual. Tissue-specific cells created in this way are used for
research and for creating and testing potential disease treatments.

"This work illustrates the power of being able to study human tissue
in a dish," said Eduardo Marba'n, MD, PhD, executive director of the
Smidt Heart Institute, who collaborated with Sharma and Svendsen on the
study. "It is plausible that direct infection of cardiac muscle cells
may contribute to COVID-related heart disease." The investigators also collaborated with co-corresponding author Vaithilingaraja Arumugaswami,
DVM, PhD, an associate professor of molecular and medical pharmacology
at the David Geffen School of Medicine at UCLA and member of the
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell
Research. Arumugaswami provided the novel coronavirus that was added
to the heart cells, and UCLA researcher Gustavo Garcia Jr. contributed essential heart cell infection experiments.

"This key experimental system could be useful to understand the
differences in disease processes of related coronaviral pathogens,
SARS and MERS," Arumugaswami said.


========================================================================== Story Source: Materials provided by Cedars-Sinai_Medical_Center. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Arun Sharma, Gustavo Garcia, Yizhou Wang, Jasmine T. Plummer, Kouki
Morizono, Vaithilingaraja Arumugaswami, Clive N. Svendsen. Human
iPSC- Derived Cardiomyocytes , are Susceptible to SARS-CoV-2
Infection. Cell Reports Medicine, 2020; 100052 DOI:
10.1016/j.xcrm.2020.100052 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200630155745.htm

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