Small dark purple spots show inflammatory cells invading the heart of a patient who died of COVID-19.
James Stone
By Emma Yasinski
ScienceCOVID-19 reports are supported by the Heising-Simons Foundation.
Three-quarters of the 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. These 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 can damage the heart – and how certain treatments can help.
The finding “paints a very good picture” of the connection between the virus and heart problems, says Joseph Maleszewski, a cardiovascular pathologist at the Mayo Clinic who was not involved in the study.
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Scientists have ample evidence of cardiac damage in patients with COVID-19. Some people, for example, have high levels of troponins, molecules released into the blood when the heart is injured. Others have experienced inflammation of the sac that surrounds the heart – and inflammation of the heart itself. But it is not clear whether these problems were caused by the SARS-CoV-2 virus attacking the heart directly or whether the damage is due to an overactive immune response.
Part of the problem is that previous studies are confused about whether SARS-CoV-2 can invade cardiac tissue. Many who I do not have found that the virus uses 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 the tissue and then making many copies of DNA from it. Once there is enough DNA, a molecule called a fluorescent tag can stick to it and shine to reveal its presence. But Stone says heart tissue is often processed and preserved with chemicals like paraffin, which can break down RNA and prevent detection to begin with.
So he and his team used another approach: in situ hybridization and the NanoString transcriptomic profile. Like RT-PCR, these techniques use special molecules to attach and detect pieces of viral RNA, but they do so without having to make copies of DNA first. The approach can identify the viral RNA even after it is broken down into smaller pieces. The scientists also analyzed about 1000 pieces of cardiac tissue – more than 20 samples from each of the 41 patients they examined. This is double the number of samples per patient in most studies, says Stone.
SARS-CoV-2 was present in 30 of the hearts, informs the team today in Modern Pathology. And only these patients experienced new atrial fibrillations, rapid and irregular heart rhythms or premature or extra heartbeat, compared to the other patients in the study – a correlation that Stone calls “quite phenomenal”.
Still, it is not clear whether the virus attacked the heart directly in these cases. Most of the infected cardiac cells were cells of the immune system, which SARS-CoV-2 could have invaded elsewhere in the body before reaching the heart. It is also unclear whether the virus – and not the immune cells themselves – is causing the problems.
Regardless, the study may help explain why the steroid dexamethasone is so useful for some patients. The drug was one of the first found to prevent deaths from severe COVID-19. It reduces inflammation, so it may have restricted the presence of immune cells that harbor SARS-CoV-2 in the heart, says Stone. Only 50% of patients treated with dexamethasone had the virus in their hearts, compared with 90% of patients who were not taking the drug.
But compared to 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 find out how it hurts the hearts of those who survive. The disease can, for example, create scar tissue that can cause heart problems in the future. We are beginning to understand what COVID-19 does to patients when they have it, he says. “What is not clear is what happens later.”