Yale researchers have conducted an experiment on “humanized mice” to try and get insight into why some people experience more severe symptoms than others when contracting the COVID-19 virus. The study found a link between the body’s inflammatory response to infection.

Researchers also found two well-known therapies, monoclonal antibodies and the steroid dexamethasone, can help treat COVID-19. The study was conducted on mice who were “engineered to possess human-like immune systems” states the Yale report published in the journal Nature Biotechnology. Researchers posed the question, “why do 80 to 90% of people infected with COVID-19 experience only mild cases while 10 to 20% face more severe or life-threatening symptoms?”

Thus far comparing the virus in humans and laboratory animals “made it difficult for scientists to pinpoint the tipping point between mild and severe cases of COVID-19.” But, the unique use of rodents with humanized immune systems offered this finding to researchers:

“If you infect a standard laboratory mouse with SARS-CoV-2 they will get infected, but not get seriously ill,” said Flavell, Sterling Professor of Immunobiology at Yale and senior author of the paper. “But our humanized mice get sick and just don’t get better. Their whole immune system is on fire.”

The research team — which was led by first author Esen Sefik, a Howard Hughes Medical Institute (HHMI) Fellow at the Damon Runyon Cancer Research Foundation — introduced SARS-CoV-2 virus taken from seriously ill human patients into the nasal passages of their humanized mice and then followed the course of the disease.

They found that the infected mice exhibited the same symptoms as severely ill human patients, such as lung damage, weight loss, and a heightened, persistent inflammatory immune response that damages tissues. They then treated the mice with monoclonal antibodies provided by Michel Nussenzweig, an immunologist at Rockefeller University and, like Flavell, an HHMI investigator. These antibodies, which specifically target the virus, were effective if given before or very early after infection but did little to stifle symptoms if administered in later stages of infections, they found.

Conversely, during the early stages of infection the immune suppressant dexamethasone was fatal to mice when it suppressed the initial immune response that was crucial to combat the virus. However, it helped clear infection during later stages of disease by suppressing the inflammatory response that had begun damaging organs.

“Early in the course of the disease, a strong immune response is crucial for survival,” Sefik said. “Later in the disease, it can be fatal.”