The repurposed mouse model sheds light on the spectrum of symptoms of COVID-19 disease

A repurposed mouse model can develop symptoms of both severe COVID-19 (lung damage, blood clots, abnormal blood vessels, and death) as well as milder diseases, including loss of smell, according to a recent study published by the University of London. ‘Iowa in Nature.

The study also showed that convalescent plasma from a patient who recovered from COVID-19 protected mice from lethal disease. The results suggest that the K18-hACE2 mouse model is useful for understanding a spectrum of COVID-19 disease symptoms and for developing and testing new treatments.

When COVID-19 began spreading around the world earlier this year, UI researchers Stanley Perlman, MD, PhD, and Paul McCray, MD, realized that a mouse model they had created ten years earlier to study SARS could be an invaluable tool for understanding new diseases and for testing potential treatments.

In the new study, Perlman, McCray and colleagues present a detailed characterization of the effects of SARS-CoV-2 infection in these K18-hACE2 mice, which are now readily available at Jackson Laboratories.

Infection with a high dose of the virus has produced many of the signs of illness seen in people with severe COVID-19, including severe lung damage, blood vessel abnormalities known as vasculitis, blood clots, and death.

The mouse develops a rather robust lung disease that is at the severe end of the spectrum. This gives us the opportunity to investigate what’s going on with COVID lung disease. Additionally, people who die from this disease often have vasculitis, which is unusual for coronavirus infections, and we have found that mice can develop signs of vasculitis in the liver, lungs and brain. “

Paul McCray, UI professor of pediatrics-pulmonology, microbiology, and immunology and Roy J. Carver Chair in Pulmonary Research

A particularly interesting finding was that infected mice lost their sense of smell. This effect, also known as anosmia, is seen in a large percentage of people who contract COVID-19, but it’s not well understood.

The study showed that K18-hACE2 mice treated with convalescent plasma and then infected with SARS-CoV-2 infection did not succumb to infection but, like many infected patients with mild disease, had loss of smell as a symptom. main.

Further investigation of the cells in the nasal passage suggested that anosmia results from the initial infection and damage to a cell type that helps support the function of nearby sensory neurons that detect odor.

“Loss of smell or taste occurs in a large percentage of patients who have COVID-19, whether they are truly sick or if that’s the only sign of illness they have. Most people get their sense of smell back. pretty quickly, but others don’t, ”says Perlman, UI professor of pediatrics, microbiology and immunology, and Mark Stinski Chair in Virology. “This mouse model opens up the possibility of learning more about how this happens, and if we could understand the mechanics of why people lose their sense of smell, it will help us heal people.”