COVID-19 Mouse Model May Hold Key to New Treatments, Understanding Risk Factors

ST. LOUIS, Mo. – Since the start of the coronavirus pandemic, scientists around the globe continue their scramble to understand SARS-CoV-2, the virus responsible for COVID-19. Despite these efforts, researchers have not yet been able to develop a vaccine and many questions about the virus remain. For example, although evidence suggests that symptom severity may be impacted by gender, vitamin D levels, blood type, and environmental factors, some of this evidence conflicts with one another. On top of that, it still isn’t entirely clear why some people infected with the virus get sicker than others. To that end, researchers at Washington University’s School of Medicine believe their recent testing on mice could help unlock some of the answers long sought.

In an effort to better understand COVID-19 and to accelerate vaccine and drug development, the research team developed a way to infect laboratory mice with the SARS-CoV-2 virus. By doing so, the researchers were able to replicate symptoms in the rodents, thus providing a way to easily and rapidly study the disease.

Why Mice?

Mice are a valuable tool for scientists studying infectious diseases. They provide a rapid and cost-efficient way to study mechanisms of viral infection and factors impacting illness trajectory without risking human health and safety.

In the case of COVID-19, however, developing a mouse model is difficult.

Unlike humans, mice are not capable of being infected with SARS-CoV-2 naturally. In humans, the virus attaches to a protein in the respiratory tract known as angiotensin converting enzyme-2 (ACE2). While mice also have an ACE2 protein, it is different from the human version, and the SARS-CoV-2 virus can’t attach to it. To work around this, researchers inserted a gene for the human ACE2 protein into mice, thus triggering production of the human ACE2 protein and rendering the mice vulnerable to SARS-CoV-2 infection.

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After exposing mice to SARS-CoV-2, scientists found that the virus caused symptoms that mimicked those in humans, such as respiratory tract inflammation and pneumonia. The virus was also found in regions outside the respiratory tract, including the heart, spleen, and brain, which are all areas that the virus targets in humans.

“The mice develop a similar lung disease to what we see in humans,” says Michael S. Diamond, MD, PhD, principal investigator and Herbert S. Gasser Professor of Medicine in a news release. “They get quite sick for a while but eventually recover, like the vast majority of people who get COVID-19. You can use this technique with almost any strain of laboratory mouse to make them susceptible to SARS-CoV-2 and then do whatever kind of study you want: test vaccines or drugs, study the immune response, and many other things related to how the virus causes disease.”

More Than Just Medicine

In addition to its utility in developing drugs and vaccines, the mouse model can also be useful to understand what factors put people at risk for severe COVID-19 symptoms and complications.

“It would be easy to study, for example, older mice or obese mice and see how they respond to infection. I’d expect that they would do substantially worse, but the real question is why,” says Diamond. “Do they have more virus in the early stages? Is their condition weakening the immune response, or perhaps exacerbating a detrimental inflammatory response? With this model, we can begin to look at some of those factors that are very hard to study in people.”

The study is published in Cell.

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