The SARS-CoV-2 virus can infect specialized pacemaker cells that maintain the rhythmic rhythm of the heart, triggering a process of self-destruction in the cells, according to a preclinical study led by researchers at Weill Cornell Medicine, the New York Presbyterian and NYU Grossman School of Medicine. The findings offer a possible explanation for the cardiac arrhythmias commonly observed in patients with SARS-CoV-2 infection.
In the study, which was reported April 1 in the Circulation Research, the researchers used an animal model as well as human stem cell-derived pacemaker cells to show that SARS-CoV-2 can easily infect pacemaker cells and trigger a process called ferroptosis, in which the cells self-destroy but also produce reactive oxygen molecules. can affect nearby cells.
“This is a surprising and seemingly unique vulnerability of these cells – we looked at a variety of other human cell types that can be infected by SARS-CoV-2, including myocardial cells, but found evidence of ferroptosis only in pacemaker cells,” said study co-author Dr. Shuibing Chen, Kilts Family Professor of Surgery and Professor of Chemical Biology in Surgery and Chemical Biology in Biochemistry at Weill Cornell Medicine.
Arrhythmias including too fast (tachycardia) and too slow (bradycardia) heart rhythms have been noted in many covid-19 patients, and several studies have linked these abnormal rhythms to worse outcomes of covid-19. However, how SARS-CoV-2 infection can cause such arrhythmias has been unclear.
In the new study, the researchers, including co-senior author Dr. Benjamin tenOever of the NYU Grossman School of Medicine, Golden Hamsters – one of the only experimental animals to reliably develop covid-19-like signs from SARS-CoV-2 infection – and found evidence that after nasal exposure, the virus can infect cells in the natural pacemaker unit. known as the sinoatrial node.
To study the effects of SARS-CoV-2 on pacemaker cells in more detail and with human cells, the researchers used advanced stem cell techniques to mature human embryonic stem cells into cells that closely resemble sinoatrial node cells. They showed that these induced human pacemaker cells express the ACE2 receptor and other factors that SARS-CoV-2 uses to enter the cells and are easily infected by SARS-CoV-2. The researchers also observed large increases in inflammatory immune activity in the infected cells.
The team’s most surprising finding, however, was that the pacemaker cells, in response to infection stress, showed clear signs of a cellular self-destructive process called ferroptosis, which involves the accumulation of iron and the flowing production of cell-destroying reactive oxygen. molecules. The researchers were able to reverse these signs in the cells with the help of compounds known to bind iron and inhibit ferroptosis.
“This finding suggests that some of the cardiac arrhythmias detected in covid-19 patients may be caused by ferroptosis damage to the sinoatrial node,” says co-senior author Dr. Robert Schwartz, associate professor of medicine at the Department of Gastroenterology and Hepatology at Weill Cornell Medicine and a hepatologist at the New York-Presbyterian / Weill Cornell Medical Center.
Although covid-19 patients could in principle be treated with ferropto 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 using their cell and animal models to investigate sinoatrial nodal damage in COVID-19 – and beyond.
“There are other human sinoatrial arrhythmias that we could model with our platform,” says co-senior author Dr. Todd Evans, Peter I. Pressman MD Professor of Surgery and Deputy Dean of Research at Weill Cornell Medicine. “And although physicians may currently use an artificial electronic pacemaker to replace the function of a damaged sinoatrial node, there is the potential to use sinoatrial cells that we have developed as an alternative, cell-based pacemaker therapy.”