For an issue once expected to occur mostly in patients with severe COVID-19, heart conditions following SARS-CoV-2 infection are much more prevalent, writes Eric Topol in a Perspective. This became especially visible following cardiac involvement in young healthy athletes who had experienced mild COVID-19. "It is vital to determine what drives this pathogenesis," says Topol. He highlights unique attributes of the virus that have resulted in it damaging the hearts of COVID-19 patients both directly (for example, through heart muscle cells) and indirectly (for example, by infecting endothelial cells that line the blood vessels to the heart). He overviews the diverse spectrum of cardiovascular issues the virus has produced - ranging from limited necrosis of heart cells to cardiogenic shock (an often-fatal inability to pump enough blood). Topol notes that recent studies of COVID-19 patients undergoing MRI or echocardiography of the heart have provided some new insights about cardiac involvement, together raising concerns that heart involvement is far more prevalent than once thought, for this disease. But overall, he says, there have been minimal cardiac imaging studies in people who test positive for the virus. This and other factors - like the lack of cardiovascular assessments for people experiencing "long-COVID" - contribute to a fundamental and large hole in our knowledge base of how this virus impacts this major organ. "It would not be surprising in the future for patients to represent with cardiomyopathy of unknown etiology and test positive for SARS-CoV-2 antibodies," he writes. He says the most intriguing question in this space is why certain individuals experience heart issues after virus infection have when others don't. Whether it's a result of an individual's inflammation response, an autoimmune phenomenon, or some other explanation needs to be clarified, says Topol. He notes how the global spread of this disease and the "panoply of disease manifestations" will make this a truly daunting task.