Are COVID-19-linked arrhythmias caused by viral damage to the heart's pacemaker cells?

Date:
April 1, 2022
Source:
Weill Cornell Medicine
Summary:
The SARS-CoV-2 virus can infect specialized pacemaker cells that
maintain the heart's rhythmic beat, setting off a self-destruction
process within the cells, according to a preclinical study. The
findings offer a possible explanation for the heart arrhythmias
that are commonly observed in patients with SARS-CoV-2 infection.



FULL STORY ==========================================================================
The SARS-CoV-2 virus can infect specialized pacemaker cells that maintain
the heart's rhythmic beat, setting off a self-destruction process within
the cells, according to a preclinical study co-led by researchers at
Weill Cornell Medicine, NewYork-Presbyterian and NYU Grossman School
of Medicine. The findings offer a possible explanation for the heart arrhythmias that are commonly observed in patients with SARS-CoV-2
infection.


==========================================================================
In the study, reported Apr. 1 in Circulation Research, the researchers
used an animal model as well as human stem cell-derived pacemaker cells
to show that SARS-CoV-2 can readily infect pacemaker cells and trigger
a process called ferroptosis, in which the cells self-destruct but also
produce reactive oxygen molecules that can impact nearby cells.

"This is a surprising and apparently unique vulnerability of these cells
-- we looked at a variety of other human cell types that can be infected
by SARS-CoV- 2, including even heart muscle cells, but found signs of ferroptosis only in the pacemaker cells," said study co-senior author
Dr. Shuibing Chen, the Kilts Family Professor of Surgery and a professor
of chemical biology in surgery and of chemical biology in biochemistry
at Weill Cornell Medicine.

Arrhythmias including too-quick (tachycardia) and too-slow (bradycardia)
heart rhythms have been noted among many COVID-19 patients, and multiple studies have linked these abnormal rhythms to worse COVID-19 outcomes. How SARS-CoV- 2 infection could cause such arrhythmias has been unclear,
though.

In the new study, the researchers, including co-senior author Dr. Benjamin tenOever of NYU Grossman School of Medicine, examined golden hamsters --
one of the only lab animals that reliably develops COVID-19-like signs
from SARS-CoV- 2 infection -- and found evidence that following nasal
exposure the virus can infect the cells of the natural cardiac pacemaker
unit, known as the sinoatrial node.

To study SARS-CoV-2's effects on pacemaker cells in more detail and
with human cells, the researchers used advanced stem cell techniques to
induce human embryonic stem cells to mature into cells closely resembling sinoatrial node cells. They showed that these induced human pacemaker
cells express the receptor ACE2 and other factors SARS-CoV-2 uses to
get into cells and are readily infected by SARS-CoV-2. The researchers
also observed large increases in inflammatory immune gene activity in
the infected cells.

The team's most surprising finding, however, was that the pacemaker cells,
in response to the stress of infection, showed clear signs of a cellular
self- destruct process called ferroptosis, which involves accumulation
of iron and the runaway production of cell-destroying reactive oxygen molecules. The scientists were able to reverse these signs in the cells
using compounds that are known to bind iron and inhibit ferroptosis.

"This finding suggests that some of the cardiac arrhythmias detected in
COVID- 19 patients could be caused by ferroptosis damage to the sinoatrial node," said co-senior author Dr. Robert Schwartz, an associate professor
of medicine in the Division of Gastroenterology and Hepatology at Weill
Cornell Medicine and a hepatologist at NewYork-Presbyterian/Weill Cornell Medical Center.

Although in principle COVID-19 patients could be treated with ferroptosis inhibitors specifically to protect sinoatrial node cells, antiviral
drugs that block the effects of SARS-CoV-2 infection in all cell types
would be preferable, the researchers said.

The researchers plan to continue to use their cell and animal models to investigate sinoatrial node damage in COVID-19 -- and beyond.

"There are other human sinoatrial arrhythmia syndromes we could model
with our platform," said co-senior author Dr. Todd Evans, the Peter
I. Pressman M.D.

Professor of Surgery and associate dean for research at Weill Cornell
Medicine.

"And, although physicians currently can use an artificial electronic
pacemaker to replace the function of a damaged sinoatrial node, there's
the potential here to use sinoatrial cells such as we've developed as
an alternative, cell- based pacemaker therapy."

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


========================================================================== Journal Reference:
1. Yuling Han, Jiajun Zhu, Liuliu Yang, Benjamin E. Nilsson-Payant,
Romulo
Hurtado, Lauretta A. Lacko, Xiaolu Sun, Aravind R. Gade,
Christina A.

Higgins, Whitney J. Sisso, Xue Dong, Maple Wang, Zhengming Chen,
David D.

Ho, Geoffrey S. Pitt, Robert E. Schwartz, Benjamin R. tenOever,
Todd Evans, Shuibing Chen. SARS-CoV-2 Infection Induces Ferroptosis
of Sinoatrial Node Pacemaker Cells. Circulation Research, 2022;
130 (7): 963 DOI: 10.1161/CIRCRESAHA.121.320518 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220401122230.htm

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