Investigators Identify Why Omicron Causes Less Severe Disease

Shortly after it was identified by South African investigators, Omicron quickly overtook Delta as the variant responsible for the vast majority of new COVID-19 infections worldwide.

Ever since its emergence, Omicron has caused mass confusion for its ability to break through vaccine protection despite eliciting less severe disease. A new study, conducted by researchers from the University of Kent and Goethe University Frankfurt, found that Omicron causes relatively milder disease because it is less effective at evading the body’s interferon response.

The investigators noticed that the Omicron isolates infected fewer cells in Calu-3 and Caco-2 cell cultures in comparison to the Delta isolate. They hypothesized that the differences in Omicron virus replication in interferon competent Calu-2 and Caco-3 cells and interferon-deficient Vero cells cause Omicron to be less effective in antagonizing cellular interferon signaling than the Delta variant.

Omicron is less effective in antagonizing the interferon response in human cells, likely contributing to the lower pathogenicity observed in patients infected with Omicron.

Additionally, the investigators found the Omicron variant is still sensitive to 8 of the most important COVID-19 treatment drugs, including EIDD-1931 (active metabolite of molnupiravir), PF-07321332 (nirmatrelvir, active ingredient of paxlovid), ribavirin, remdesivir, favipravir, nafamostat, camostat, and aprotinin.

“Our study provides for the first time an explanation, why Omicron infections are less likely to cause severe disease. Obviously, Omicron can in contrast to Delta not effectively inhibit the host cell interferon immune response,” Martin Michaelis, one of the study authors and a professor at the University of Kent’s School of Biosciences, said in a statement.