United States.- The reason some cases of COVID are more severe than others is the body’s viral inflammatory response

Madrid, 25 (Europa Press)

Researchers in Richard Flawell’s laboratory at Yale University in the United States wondered why 80 to 90% of people infected with COVID-19 have only mild cases, while between 10 and 20% suffer more severe or life-threatening complications. Does matter. symptoms, and turns out that the cause may lie in the antiviral inflammatory response of each patient’s body.

For their research, they designed laboratory mice to have immune systems similar to those of humans, and these “humanized mice” showed that the cause of severe COVID may lie in our own antiviral inflammatory response to the virus, according to Nature Biotechnology. ‘ reports in the magazine.

The study also showed that two well-known treatments – the use of monoclonal antibodies and the steroid dexamethasone – can help treat COVID-19 infection. But in the case of antibodies, treatment is effective only if it is given in the early stages of the disease. In the case of steroids, this is only effective if they are administered during the later stages of the disease.

The different immune system responses to the virus seen in standard laboratory animals and humans have made it difficult for scientists to determine the tipping point between mild and severe COVID-19 cases. However, Flavelle’s mice, which are designed to have the same immune system as humans, offer an opportunity to answer the question.

“If you infect a standard laboratory mouse with SARS-CoV-2, it will become infected, but it will not become seriously ill,” says Flawell, a Sterling professor of immunobiology at Yale and lead author of the paper. But our humanized mice get sick and do not recover. His entire immune system is on fire.

The research team, led by first author Essen Cefik of the Damon Runyon Cancer Research Foundation’s Howard Hughes Medical Institute (HHMI), introduced SARS-CoV-2 virus taken from critically ill human patients into the nostrils of their humanized mice and then Followed the course of the disease.

They found that the infected mice displayed symptoms similar to those of critically ill human patients, including lung damage, weight loss, and a persistent and highly inflammatory immune response that damages tissues.

They then treated the mice with monoclonal antibodies provided by Michelle Nusenzwig, an immunologist at Rockefeller University and, like Flawell, an HHMI researcher. These antibodies, which specifically target the virus, were effective when given very soon before or during infection, but did little to alleviate symptoms when given later in infection, they found.

In contrast, during the early stages of infection, the immunosuppressant dexamethasone was lethal to mice by suppressing the initial immune response, which was important for fighting the virus. However, it helped ward off infection during the later stages of the disease by suppressing the inflammatory response that was damaging the organs.

“Early on in the disease, a strong immune response is important for survival,” Sefik says. Later in the disease it can also be fatal.

Humanized mouse models may also reveal strong clues about the causes and possible treatments for the long and severe so-called COVID, the scientists go on.