COVID: By killing heart muscle cells, coronavirus disrupts contraction

COVID-19 is now known to affect many organs besides the lungs, including the pancreas, liver, brain, and even the heart. Since the start of the pandemic, many patients have complained of chest pain, palpitations (due to arrhythmia) and extreme fatigue. Researchers have therefore been trying to elucidate the mechanisms involved, and in particular to understand whether the alteration of cardiac tissues is directly due to the viral infection or rather to the inflammation which results from it. A new study shows that tissue damage is mainly due to viral replication inside the heart.

Researchers at Washington University School of Medicine in St. Louis provide evidence that heart damage in COVID-19 patients is caused by the virus invading and replicating inside cells heart muscle, causing cell death and interfering with heart muscle contraction. ” We provide evidence that cardiomyocytes are infected in patients with myocarditis due to COVID-19 and are vulnerable to SARS-CoV-2 The researchers write in the document.

To determine this, they used stem cells to make heart tissue in an attempt to model human infection. Their method, in addition to providing clues to how best to treat coronavirus infections that affect the heart, could also be used to study the disease at large and help in the development of new therapies. The study was published on February 26 in the Journal of the American College of Cardiology: Basic to Translational Science.

Direct infection of heart muscle cells

At the start of the pandemic, we had evidence that this coronavirus can cause heart failure or heart damage in generally healthy people, which was alarming for the cardiology community. Said senior author Kory J. Lavine, associate professor of medicine. ” Even some varsity athletes who had been cleared to resume competition after COVID-19 infection later had heart scars. There has been some debate as to whether this is due to a direct infection of the heart or a systemic inflammatory response that occurs due to lung infection. “. ” Our study is unique because it definitely shows that in patients with COVID-19 who have developed heart failure, the virus infects the heart, specifically the cells of the heart muscle. “.

Lavine and his colleagues, including his collaborators Michael S. Diamond, professor of medicine Herbert S. Gasser, and Michael J. Greenberg, assistant professor of biochemistry and molecular biophysics, also used stem cells to design tissues that model the how human heart tissue contracts. By studying these models of heart tissue, they determined that a viral infection not only kills heart muscle cells, but destroys the muscle fiber units responsible for muscle contraction.

In this image of the artificial heart tissue used in the study, we can see human heart muscle cells (in red) infected with SARS-CoV-2 (in green). © Lina Greenberg

They also showed that this cell death and loss of heart muscle fibers can occur even in the absence of inflammation. ” Inflammation can be a second hit in addition to the damage caused by the virus, but the inflammation itself is not the initial cause of the heart injury. », Specifies Lavine.

SARS-CoV-2 and heart damage: a unique immune interaction

Other viral infections have long been associated with heart damage, but Lavine said SARS-CoV-2 is unique in the effect it has on the heart, especially on immune cells that respond to it. infection. In COVID-19, immune cells called macrophages, monocytes, and dendritic cells dominate the immune response. For most of the other viruses that affect the heart, it is the T cells and B cells of the immune system that are involved.

COVID-19 causes a different immune response in the heart compared to other viruses, and we don’t yet know how to interpret this ”Lavine said. ” In general, immune cells that respond to other viruses tend to be associated with relatively short-lived illness that resolves with supportive care. But the immune cells we see in patients with COVID-19 tend to be associated with chronic disease that can have long-term consequences. These are associations, so we will need more research to understand what is going on. “.

Results supported by real cases

If these questions of causation in heart damage have been difficult to answer, it is in part because of the difficulty in studying heart tissue in patients with COVID-19. The researchers were able to validate their findings by studying tissue from four COVID-19 patients who had heart damage associated with the infection, but more research is still needed. To this end, Lavine and Diamond are working on the development of a mouse model of heart injury. To underscore the urgency of this work, Lavine emphasizes the insidious nature of the heart damage that COVID-19 can cause.

Even young people who have had very mild symptoms can later develop heart problems that limit their ability to exercise. ”Lavine said. “ We want to understand what is happening so that we can prevent or treat it. In the meantime, we want everyone to take this virus seriously and do their best to take precautions and curb the spread, to prevent an even bigger epidemic of preventable heart disease in the future. “.

Journal of the American College of Cardiology: Basic to Translational Science

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