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Coronavirus can infect heart cells in the laboratory


DZHK researchers could show in laboratory models that SARS-CoV-2 can affect heart muscle cells. | Copyright: Julian Wagner


In laboratory models, the coronavirus can directly infect heart muscle cells, a team from several working groups at the German Centre for Cardiovascular Research (DZHK) found out. However, the virus uses a slightly different mechanism than in lung cells. If a direct infection of the heart could be detected in the human body, they would already have a drug candidate on hand.

SARS-CoV-2 mainly attacks the lungs, but some patients also get heart problems. Researchers at the German Centre for Cardiovascular Research wanted to know whether the heart problems arise due to the lungs' inflammation or whether the virus can also directly infect cells of the cardiovascular system.

Virus isolate of the first German corona patient used

"We used all available laboratory models from various DZHK locations for this," says Stefanie Dimmeler from the Goethe University in Frankfurt, who coordinated the experiments.

The first thing they did was to examine heart cells from pluripotent stem cells. These are cells that are reprogrammed from other body cells to heart muscle cells. They added two isolates of the first German corona patient, who had returned to Germany from Wuhan in March.

The researchers showed that the cells absorb the virus, that the viral RNA multiplies, and that the virus-typical spike protein is produced. The fluid above the cells, in turn, infected other cells that are usually used for such experiments in the laboratory, which is also evidence that the virus infected the heart cells.

The heartbeat of mini hearts gets faster

They also looked at the "heartbeat", because heart cells twitch in the test-tube like mini hearts. "The cells get stressed when they are exposed to the virus. The so-called 'beating rate' first goes up steeply and then drops after three days because the cells die," Dimmeler explains.

The researchers built small cell clumps from heart muscle cells, blood vessel cells, and connective tissue cells to replicate the heart as an organ. They also proved that the spike protein is produced in these. Finally, they used the same methods to study real human heart tissue, in which the virus also replicated.

Potential drug for heart infection

When the scientists added drugs such as Remdesivir to all the experiments, which prevented the virus from attacking heart cells, they detected no increase in viral RNA and spike protein - the virus could not replicate.

The exciting thing is that heart muscle cells lack the membrane protein TMPRSS2, which the coronavirus needs in lung cells besides the ACE2 receptor to enter the cells. In heart muscle cells, it uses another protein, cathepsin, for this purpose. The drugs that inhibit this protein are called cathepsin inhibitors, and in laboratory tests, they have been able to stop the virus from multiplying in heart muscle cells.

To what extent this can be transferred to patients is still unclear. "The heart muscle cells are normally well protected because the virus first has to penetrate the vascular barrier. To examine the viral infestation of the heart in the human body during the acute phase, we would have to regularly take heart-biopsies from patients with the disease, which is almost impossible," says Dimmeler. But she can imagine that patients with problematic heart reactions could be treated with cathepsin inhibitors.

DZHK sites involved: Hamburg, Frankfurt, Munich, Berlin

Original publication: SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes.  Bojkova et al., Cardiovascular Research, cvaa267, https://doi.org/10.1093/cvr/cvaa267

Scientific contact: Prof. Stefanie Dimmeler, Goethe University Frankfurt am Main, Institute for Cardiovascular Regeneration - Centre for Molecular Medicine, dimmeler(at)em.uni-frankfurt.de