Early in the pandemic, other clinicians noted that even some patients who didn’t have preexisting heart conditions experienced cardiovascular damage while fighting COVID-19 infections, pointing to a possible causative link. Researchers had found, for example, that 8–12 percent of hospitalized COVID-19 patients had elevated levels of muscle contraction–regulating proteins called troponins—a sign of heart damage—and that these patients had an increased risk of mortality compared with those who didn’t have excess troponins. And early observations of patients in China who suffered reduced ejection fraction—the amount of blood getting pumped out of the heart each time it contracts—led researchers to suggest that these individuals were likely experiencing myocarditis, a severe form of inflammation that can weaken the heart and is commonly associated with infections.

But Stone and his collaborators’ analysis of heart tissue from 21 patients who died of COVID-19, published today (September 24) in the European Heart Journal, shows that while 86 percent of the patients did have inflammation in their hearts, only three had myocarditis. Several had other forms of heart injury, such as right ventricular strain injuries.

“The problem we identified in this study is that there’s other types of myocardial injury in these patients that is also causing elevated troponins,” says Stone. His international team sought to determine the mechanisms through which the disease damaged the heart and found that some conditions “really haven’t been talked about at all in the [COVID-19] papers that have previously been published.”

The pathologists observed a median of 20 slides from each heart, which is more than are included in most other studies regarding COVID-19’s cardiac effects.

The researchers expected to find some macrophages, a type of white blood cell that indicates inflammation, as pathologists had observed macrophages in the hearts of SARS patients during the 2003 outbreak. But Stone says he was surprised to see just how common these were—18 out of 21 COVID-19 patients’ hearts harbored macrophages that exhibited this type of inflammation. “It was really quite extensive,” he says.

As they analyzed the hearts further, the pathologists noted that only three patients had myocarditis, while four showed signs of heart injury due to right ventricular strain and another four had small blood clots in the vessels in the heart. It’s not clear why patients experience such inconsistent cardiac issues.

Abela says these findings have implications for treatment. For example, if the patient has right heart failure, a condition where the right side of a patient’s heart is not pumping enough blood to the lungs, a device that mechanically helps the heart pump blood might help, rather than drugs that target the inflammation or infection, which could be used to treat myocarditis.

Because so many of the hearts were infiltrated by macrophages, the researchers say that it may be difficult to discern who is experiencing myocarditis, which is characterized by different inflammatory cells—lymphocytes—while patients are alive. The two cell types would appear similar on tests that image the hearts of living patients. So, the team looked back at the patients’ medical records to see if they could find patterns in clinical tests that would reveal the type of heart damage when it still might be treatable. The three patients with myocarditis all had both troponin levels above 60 ng/mL and abnormal ECG readings while in the hospital. Only 15 percent of the patients without myocarditis had this combination.

The findings need to be replicated in larger groups of patients but could help doctors determine the best course of treatment for heart damage due to COVID-19, Stone says. The study is “giving the cardiologists and the ICU doctors that are taking care of these patients a roadmap of the changes that are going on in the heart.”