Scientists and medical professionals worldwide are collaborating to discover how to address the coronavirus pandemic and to better understand its effects on the body. It is well known that COVID-19 can devastate the lungs, causing symptoms including cough, shortness of breath, pneumonia, and acute respiratory distress syndrome. However, there is mounting evidence that the coronavirus may directly or indirectly infect other cell types as well. Of particular interest is how the coronavirus affects the heart. About 20-30% of patients hospitalized with COVID-19 have cardiac injury, such as arrythmia, inflammation of the heart, or heart attack, which is associated with higher risk of death. Those that recover from COVID-19 can exhibit cardiac dysfunction for months afterwards, even if they exhibited only mild COVID-19 symptoms. Researchers are using stem cell models to study coronavirus infection in the lab to determine how different cell types in the body are affected.

An important question to address is whether cells are indirectly or directly infected by the coronavirus. In the cardiovascular system, heart cells may be injured indirectly by a lack of oxygen supply to the heart due to COVID-19’s impact on the lungs, or the virus may directly infect heart muscle and associated blood vessels. Direct damage to the heart muscle cells could lead to heart rhythm problems or heart failure, while direct damage to blood vessel cells could impair circulation. Insight into the infection process and the resulting impact can improve our understanding of the disease and lead to the development of safe and effective treatment options.

Initial clinical studies indicate that coronavirus infection can directly cause injury to the heart, resulting in a dangerous condition known as myocarditis, a condition where immune cells are hyperactivated in the heart muscle. Otherwise healthy individuals who are infected with coronavirus can exhibit this inflammation of the heart, which in severe cases can lead to cardiac arrest. Even high-level college athletes have been observed to develop myocarditis after coronavirus infection. Initial reports indicate that about 15% of these athletes that recovered from COVID-19 showed signs of myocarditis, whether or not they ever showed COVID-19 symptoms.

To address whether coronavirus indirectly or directly infects different cells in the body scientists can use human induced pluripotent stem cells (hiPSCs), which are made from a small sample of skin or blood. These are powerful stem cells that can be transformed into various cell types and then infected with the coronavirus in order to study the infection process and the resulting effects on the body. Using this method, researchers have shown that both stem cell-derived heart muscle cells and blood vessels are directly susceptible to coronavirus infection. This is not true of cells in all tissues.  Some types of brain tissue, for example, cannot be directly infected by the coronavirus. These laboratory studies parallel clinical reports that some tissues are more susceptible to coronavirus infection than others.

Scientists found that after stem cell-derived heart muscle cells were infected with coronavirus, some cells stopped beating and died within three days. Infection also led to an immune response and an attempt to alleviate the viral infection. Researchers can now use these infected heart cells to screen for drugs that can improve their function and survival. These cells could also be used to identify new antiviral drugs that could directly and specifically reduce coronavirus replication in the heart, potentially reducing cardiac injury and limiting the spread of the virus. Scientists are also using the cells to study COVID-induced myocarditis by adding immune cells to their experiments.

The extent and conditions in which the coronavirus impacts the heart and blood vessels is becoming more clear as scientists learn more about the virus using these human iPSC models. However, better clinical data is needed to understand the different ways that infection directly and indirectly affects the cardiovascular system in patients. Human iPSC models could help identify potential new treatments that could alleviate both of these types of cardiovascular complications, leading to better outcomes for COVID-19 patients. Stem cell models are a valuable ally to the global stem cell research community, which is working collaboratively on many fronts to fight coronavirus and COVID-19.

Blog by guest contributor Arun Sharma, PhD, postdoctoral fellow in the lab of Clive Svendsen, PhD at Cedars Sinai, CA, USA.