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Many people who die of COVID-19 have the virus in their hearts - Science Magazine

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Small, dark purple spots show inflammatory cells invading the heart of a patient who died of COVID-19.

James Stone

Science’s COVID-19 reporting is supported by the Heising-Simons Foundation.

Three-quarters of people who died of COVID-19 harbored the SARS-CoV-2 virus in their hearts, according to the most detailed study of cardiac tissue to date. Those people were also more likely than patients without cardiac invasion to experience abnormal heart rhythms before they died. The study offers insight into how the disease may damage the heart—and how certain treatments may help.

The finding “paints a really nice picture” of the connection between the virus and heart problems, says Joseph Maleszewski, a cardiovascular pathologist at the Mayo Clinic who was not involved with the study.

Scientists have ample evidence of heart damage in COVID-19 patients. Some people, for example, show elevated levels of troponins, molecules released in the blood when the heart is injured. Others have experienced inflammation of the sac surrounding the heart—and inflammation of the heart itself. But it’s been unclear whether these problems were caused by the SARS-CoV-2 virus attacking the heart directly, or the damage is due to an overactive immune response.

Part of the problem is that previous studies are mixed about whether SARS-CoV-2 can invade heart tissue. Many that haven’t found the virus use real-time polymerase chain reaction (RT-PCR), says James Stone, a cardiovascular pathologist at Massachusetts General Hospital. RT-PCR works by detecting viral RNA in tissue, then making many DNA copies of it. Once there’s enough DNA, a molecule called a fluorescent tag can stick to it and shine to reveal its presence. But Stone says that heart tissue is often processed and preserved using chemicals like paraffin, which can break down the RNA and prevent detection to begin with.

So he and his team used another approach: in situ hybridization and NanoString transcriptomic profiling. Like RT-PCR, these techniques use special molecules to attach to and detect pieces of viral RNA, but they do so without having to make DNA copies first. The approach can identify viral RNA even after it’s broken into smaller pieces. The scientists also analyzed about 1000 pieces of heart tissue—more than 20 samples from each of the 41 patients they looked at. That’s double the number of samples per patient in most studies, Stone says.

SARS-CoV-2 was present in 30 of the hearts, the team reports today in Modern Pathology. And only those patients experienced new atrial fibrillations, fast and irregular heart rhythms, or early or extra heartbeats, compared with the other patients in the study—a correlation Stone calls “pretty phenomenal.”

Still, it’s unclear whether the virus attacked the heart directly in these cases. Most of the infected cardiac cells were immune cells, which SARS-CoV-2 could have invaded elsewhere in the body before they traveled to the heart. It’s also unclear whether the virus—rather than the immune cells themselves—is causing the problems.

Regardless, the study may help explain why the steroid dexamethasone is so helpful to some patients. The drug was one of the first found to prevent deaths from severe COVID-19. It reduces inflammation, so it may have curbed the presence of SARS-CoV-2–harboring immune cells in the heart, Stone says. Only 50% of the patients treated with dexamethasone had the virus in their hearts, compared with 90% of patients who were not on the drug.

But compared with large clinical trials, the number of patients in this new study is small, making it impossible to say that one drug protects the heart better than another, says Nicholas Hendren, a cardiology fellow at the University of Texas Southwestern Medical Center.

Still, Maleszewski says the new findings are a call to action. Scientists need to probe more cardiac tissue, he argues, not just to see how COVID-19 kills patients, but to figure out how it hurts the hearts of those that survive. The disease may, for example, create scar tissue that can cause cardiac problems down the line. We’re starting to understand what COVID-19 does to patients when they have it, he says. “What’s not clear is what happens later on.”

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