. Scientific Frontline: Omicron causes less severe illness in animal models than previous variants

Friday, January 21, 2022

Omicron causes less severe illness in animal models than previous variants

A new study confirms that, compared to earlier versions of the SARS-CoV-2 virus, the omicron variant causes less severe disease in mice and hamsters, which are reliable models for understanding COVID-19.

Yoshihiro Kawaoka
The findings, previously available as a preprint and published following peer review today (Jan. 21) in the journal Nature, align with preliminary data from studies of people infected with the variant and offer insight into the nature of the disease with omicron. The variant emerged in late November 2021 and was first identified by scientists in Botswana and South Africa.

Led by Yoshihiro Kawaoka at the University of Wisconsin–Madison, along with Michael Diamond and Adrianus (Jacco) Boon at the Washington University School of Medicine in St. Louis, the collaborative effort was the work of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases.

“SAVE meets four times per week,” Kawaoka explains, and includes teams analyzing sequences from viruses isolated across the world and screening for new variants; teams studying the biology of new variants in animal models; and teams working to isolate viruses for study, examining viral replication and testing how well previous infection or vaccination provides protection against emerging variants. Researchers who typically compete for publications and funding have come together in light of the COVID-19 crisis.

Peter Halfmann
Peter Halfmann, a research associate professor at UW–Madison, was among the first in the world to isolate the omicron variant from human samples for study. The samples came from infected patients in Wisconsin, New York, Georgia and Tokyo, and each contained slight sequence differences.

Once the viruses were isolated from the samples, scientists throughout the SAVE network began to test them in mice and hamsters. Animal studies are an important step in understanding new variants and how well they respond to existing countermeasures, such as vaccines and therapies.

The spike protein of omicron contains more than 30 mutations — a striking number relative to earlier variants. Because current vaccines and antibody treatments are based on these earlier versions, researchers were concerned that vaccines and therapies would be rendered less effective.

Computer models and studies that looked at the binding capacity of the virus to ACE2 receptors, which grant the virus entry into cells, also suggested that omicron would better attach to cells.

Despite this, the researchers were surprised to find that four different strains of mice and two strains of hamsters that were exposed to the omicron variant experienced less severe disease than when they were exposed to earlier versions of the virus, including the beta and delta variants. (All of the variants they tested were capable of infecting rodents.)

The animals lost less weight and experienced milder illness, experiencing no significant changes in their lung function and fewer signs of disease in their lungs.

Animals genetically modified to possess human ACE2 receptors saw slightly more disease when exposed to omicron, but still did not become as ill as those infected with earlier versions of the virus.

This single study alone can’t fully explain why omicron behaves differently. But the scientists cite another pre-print study that shows omicron makes copies of itself more quickly in areas of the upper respiratory tract relative to deeper regions of the lungs, which could limit its severity while also making the variant more readily transmissible.

There is also much the study does not address, such as the effect of omicron on other organs, or how well the variant responds to vaccine-induced immunity or to treatments. However, efforts are underway to answer these questions, both in animal models and in people.

In fact, a study published Jan. 19 in Nature, co-authored by Kawaoka and led by Diamond, shows that existing therapeutic monoclonal antibodies used to treat infections with earlier variants are less effective against omicron.

The study demonstrates that looking at each mutation in isolation or trying to make predictions based solely on the number of mutations can’t reliably tell us about the behavior of the virus. That’s especially true, says Kawaoka, a professor of pathobiological sciences at the UW–Madison School of Veterinary Medicine, given that most people in the U.S. by now — two years into the pandemic — are either vaccinated or have been exposed to the virus, or both.

“The sequence information and modeling may not predict what happens in humans,” he explains.

The research collaboration was made possible because of efforts between researchers across the globe who pooled data, shared materials and expertise, and were able to tell a more complete story than any individual effort alone. It was also made possible by the contributions of others at UW–Madison and at the Wisconsin State Laboratory of Hygiene, including Allen Bateman, Samantha Loeber, Jorge Osorio and Kelsey Florek.

Source/Credit: University of Wisconsin–Madison / Kelly April Tyrrell


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