Omicron's mutations explain why it is less severe among vaccinated

Brazilian researchers have found that Omicron has mutations detected in previous variants and that is the reason why it is less severe among the vaccinated.

Omicron emerged as a variant of concern only in November 2021, but all the mutations it contains, except one, had been described before that.

Researchers at the Federal University of Sao Paulo (UNIFESP) in Brazil attribute this factor to the effectiveness of the existing vaccines against the variant, reflected in the relatively small number of severe cases and deaths despite Omicron's heightened transmissibility.

The hypothesis is raised in an article by the scientists published in the Journal of Medical Virology (JMV) as a Letter to the Editor.

"In light of the data available so far, we believe the existing vaccines are indeed effective against all variants of the virus, all things considered. They may also be effective against any other variants that emerge in future," said Ricardo Duraes-Carvalho, researcher affiliated with the university's medical school (EPM-UNIFESP).

Before the emergence of Omicron, a separate study led by Duraes-Carvalho described several mutations shared by a number of variants.

The group analysed more than 200,000 genomes of SARS-CoV-2 and other human coronaviruses.

In the paper published on the preprint and not yet peer-reviewed, the team found identical mutations in different strains, which could serve as targets for future vaccines.

"Omicron corroborates our study. Out of 35 mutations in the variant's spike protein [used by SARS-CoV-2 to bind to a specific receptor when infecting human cells], only one was unknown. Twenty-five were in RBD (receptor-binding domain) 15 and RBM (receptor-binding motif) 10, regions of the virus that bind to human cells and are therefore potential targets for neutralising antibodies," Duraes-Carvalho said.

"That may explain why vaccination has so far been effective even though none of the vaccines on the market was designed specifically for Omicron. They don't prevent transmission, but they prevent severe cases and deaths," Robert Andreata-Santos, postdoctoral fellow at EPM-UNIFESP wrote in the JMV.

In the study posted to the preprint platform, Duraes-Carvalho and team analysed the dynamics of viral dissemination and evolution over time in Brazil, the US, and India, for the period between February and August 2021.

The analysis showed an increase in the number of mutation sites in the viral genome, above all in the spike protein, configuring what the researchers term convergent evolution. This means that different variants undergo identical mutations that confer advantages such as evading the host's immune system or binding more efficiently to human cells.

Nine directional spike mutation sites were detected prior to February 2021, followed by 14 between then and July. With the spread of the Delta variant, more spike protein mutations were observed, as well as signs of recombination, one of the factors that can lead to the emergence of novel variants.

Recombination is rearrangement of genetic material, especially by the joining of DNA segments from different strains. Signs of recombination involving Omicron were also observed.

In December, the researchers analysed 146 Omicron-genome sequences from Australia, Austria, Belgium, Botswana, Canada, England, Germany, Hong Kong, Israel, Italy, and South Africa. Evidence of recombination was found when sequences from Beta, Delta and Omicron were aligned, suggesting that co-circulation of several variants may enhance recombination events.