Should we worry about a dangerous Omicron-Delta hybrid variant?

Coronaviruses like SARS-CoV-2 can exchange genetic material when they infect the same host. Given that both the Omicron and the Delta variant are circulating in many parts of the world, it is possible that a new variant emerges that combines the unfavourable features of both of them. By Martin Michaelis and Mark Wass.

The SARS-CoV-2 variant Omicron (B.1.1.529) is now dominant in many countries. It is more infectious than previous variants and better at infecting individuals with pre-existing immunity from previous SARS-CoV-2 infections and vaccinations.

However, Omicron is also associated with proportionally fewer hospitalisations and deaths than previous variants. This reduced pathogenicity is commonly attributed to enhanced immunity levels in the population. In particular, fully vaccinated individuals, who received an additional booster vaccination, still seem to be protected from severe disease.

However, evidence is emerging that Omicron is also inherently less pathogenic than previous variants. Omicron variant viruses cause less severe disease in animal models. Moreover, we have recently shown that Omicron variant viruses are less effective than Delta variant viruses in antagonising the interferon response in human cells than Delta [1,2]. This provides the first mechanistic explanation why Omicron infections are associated with more favourable clinical outcomes.

However, the finding that Omicron is intrinsically less pathogenic than previous SARS-CoV-2 variants may have further implications for the ongoing pandemic. Coronaviruses including SARS-CoV-2 can recombine their genetic material when two viruses infect the same cell. Although we do not yet know the exact reason for the reduced ability of Omicron variant viruses to antagonise the human cell interferon response, it will most likely be separate from Omicron’s immune escape changes. Hence, it appears possible that a variant could be formed that combines the immune escape properties of the Omicron variant with the enhanced pathogenicity of the Delta variant, if both an Omicron and a Delta virus infect the same individual. Given that both variants currently spread at high levels often in the same population, such a scenario does not appear that unlikely.

Hence, surveillance will be more critical than ever in following the emergence of new SARS-CoV-2 variants. Moreover, this example highlights that we cannot automatically assume that COVID-19 will become milder over time. With an increasing number of more distantly related variants, the risk increases that new dangerous viruses emerge by genomic recombination, for example an Omicron-Delta hybrid that combines the high transmissibility and immune escape features of the Omicron variant with the pathogenicity of the Delta variant.


  1. Bojkova D, Widera M, Ciesek S, Wass MN, Michaelis M, Cinatl J jr. Reduced interferon antagonism but similar drug sensitivity in Omicron variant compared to Delta variant SARS-CoV-2 isolates. Cell Res. 2022 Jan 21:1-3. doi: 10.1038/s41422-022-00619-9.
  2. Bojkova D, Rothenburger T, Ciesek S, Wass MN, Michaelis M, Cinatl J jr. SARS-CoV-2 Omicron variant virus isolates are highly sensitive to interferon treatment. biorXiv 2022 Jan 24:2022.01.20.477067. doi: 10.1101/2022.01.20.477067.