A new perspective in the fight against COVID-19
Elizabeth Wayne has received funding through the NSF RAPID program to study an often-ignored cellular factor in the mortality rate of COVID-19.
Carnegie Mellon University Assistant Professor of Chemical Engineering and Biomedical Engineering Elizabeth Wayne has received funding from the National Science Foundation through their Rapid Response Research (RAPID) program to study an often-ignored cellular factor in the mortality rate of SARS-CoV-2 induced disease, COVID-19.
Source: Carnegie Mellon University
Elizabeth Wayne, assistant professor of Chemical Engineering and Biomedical Engineering
Much of the current research on COVID-19 has focused on cells found in the nasal passages, cell linings of vessels, and the gastrointestinal tract, as these are the cells most susceptible to SARS-CoV-2 virus infection and replication. The thought is that to fight the virus, you have to target the cells that help it spread, and in doing so, stop it from proliferating in the body.
But Wayne is taking a different approach, by studying a previously overlooked cell type: one that plays a major role in the body’s innate immune system.
“Monocytes and macrophages are members of your innate immune system,” says Wayne. “Their main job is to maintain balance in the body. For instance, when an injury or infection occurs, monocytes go to the tissue and start the process of cleaning the tissue. Then, when the injury or infection is taken care of, they switch their response to a healing phenotype. However, when these cells aren’t able to switch their inflammatory response, the body experiences an imbalance that can lead to uncontrolled inflammation.
"Think of it like driving in a car. In a healthy person, these cells have the ability to speed up and slow down. When you press on the breaks, the car stops—or in this case, the inflammatory immune response resolves itself. But what if when you pressed on the breaks, the car sped up instead? This kind of disrupted wound healing is a hallmark of disease, and that’s exactly what we’re seeing with COVID-19.”
According to Wayne, monocytes could be key in understanding why COVID-19 is so deadly to some, but not others. Clinical studies have shown that more than 70% of people who are dying of the virus also suffer from a pre-existing condition such as diabetes (30%), hypertension (74%), or cardiovascular issues (24%).1 These pre-existing conditions on their own can cause the cells of these patients’ innate immune systems to secrete elevated levels of cytokines, the cells responsible for causing the inflammatory immune response that helps to combat the condition.
While the COVID-19 causing agent SARS-CoV-2 doesn’t use monocytes to help it multiply in the patient’s body, it is able to alter their function, and essentially turn their ‘turn off’ function into a ‘speed up’ function. This means that instead of reducing inflammation in the lungs, they make the inflammation worse, leading to increased lung damage.
We need to better understand why people with preexisting conditions are more susceptible to mortality due to COVID-19.
Elizabeth Wayne, Assistant Professor, Chemical Engineering, Biomedical Engineering
“We need to better understand why people with preexisting conditions are more susceptible to mortality due to COVID-19,” says Wayne. “Our findings might also help us understand why people who seemingly don’t have preexisting conditions are also dying of COVID-19. Just because someone hasn’t been diagnosed with a preexisting condition, doesn’t mean their immune system isn’t already irregular. There are people who are prehypertensive, who might develop it in five or ten years.”
Knowing how these cells affect the deadly potential of this virus will help doctors and researchers predict whether the virus will become deadly for certain patients, and use that information to make decisions on how best to treat them. For instance, in the discussion around COVID-19, there has been some conflicting information around whether or not existing drugs could be effective in treating the virus. This research could help answer those questions.
In fact, it is Wayne’s hope that furthering the scientific understanding how monocyte function correlates with COVID-19 mortality could change the way we approach treatment for a number of different viruses.
“Since many viruses target cell surface receptors that regulate immune response, this research could in the future have a huge impact on how we treat viruses of all kinds, including things like Zika and Ebola. In particular, it could help doctors decide whether to treat patients with preexisting drugs, or whether new drugs need to be developed.”