A Vall d'Hebron study finds a mechanism used by SARS-CoV-2 that relates to its transmissibility

The variants of the virus at the beginning of the pandemic presented defective genomes in the spike gene, that is, some viral particles lacked part of the key genomic material to infect new cells.


Since the beginning of the pandemic, several SARS-CoV-2 variants have emerged that have been able to become dominant and displace those that existed until now. The variants appear as a consequence of the mutation process that takes place when the viral genome is replicated or copied, and the variant that prevails is the one that has a biological advantage over the rest. To increase its transmissibility, a Vall d'Hebron study has found that the virus benefits from a mechanism to produce or stop producing defective genomes, i.e. genomes that lose part of their genetic material. The results have been published in the journal Scientific Reports and are the result of a study led by the Liver Diseases and Microbiology groups of the Vall d'Hebron Research Institute (VHIR) with the Microbiology, Clinical Biochemistry and Preventive Medicine Services of the Vall d'Hebron University Hospital.

The researchers have studied the majority variants in each wave from the beginning of the pandemic until now. In a first study published in 2020, the same team found that the variants that appeared at the beginning of the pandemic had a significant proportion of defective genomes in the spike gene of the virus, meaning that some viral particles were missing part of their genetic material. Since the spike is key to infecting new cells, for a variant to generate defective genomes with an incomplete spike means that some of the new viral particles will not be able to infect. "This mechanism of defective genomes allows the virus to make an infection milder, or even asymptomatic, and then symptoms manifest later or do not require medical attention. In this situation, the person could decrease the guard and this would favor the transmission of the virus among the closest people", explains Dr. Josep Quer, principal investigator of the Liver Diseases group at VHIR and researcher at the Liver Diseases area of CIBER (CIBEREHD). "What can be an advantage for one variant to prevail over the others, can be a disadvantage when epidemiological conditions change", he adds.

Later, it was observed that the Alpha, Beta or Delta variants no longer had defective genomes. "These variants had other mutations that allowed them to become more easily transmitted by other mechanisms, as well as changing to become less recognizable by the human immune system", says Dr. Andrés Antón, head of the Respiratory Virus Unit of the Microbiology Service of the Vall d'Hebron University Hospital and researcher of the Microbiology research group at VHIR. "The fact that they stop producing defective genomes makes the viral particles more efficient in infecting new cells", he explains. Although the loss of defective genomes could be associated with more severe cases, the increasing vaccination rate has played a key role in reducing mortality.

With the introduction of the Omicron variant, the work showed that the virus also had defective genomes, making it more similar to the early pandemic variants than to the Delta variant. This finding ties in with previous studies that argue that Omicron does not provide a continuous evolution of variants like Delta, but may have been the result of other evolutionary lines. "Omicron accumulates many other mutations that allow the virus to escape immune system recognition and infect more efficiently. These mutations also make it infect mostly the upper respiratory tract (nose and neck), which facilitates its transmission, since the virus can be transmitted more easily just by breathing or with a slight cough", says Dr. Quer.

The work has gone further, and the study of Omicron and the subvariants that have emerged shows that the same pattern seen with the variants from the beginning of the pandemic to Delta is repeated, so that the new subvariants that have appeared in recent months no longer have defective genomes.

The study has been funded by the General Directorate for Health Research and Innovation (DGRIS) of the Department of Health, the CIBER of Infectious Diseases (CIBERINFEC) and the CIBER of Liver and Digestive Diseases (CIBEREHD) of the Instituto de Salud Carlos III and the Center for the Development of Industrial Technology (CDTI) in collaboration with Roche Diagnostics.

The work shows that the Alpha, Belta or Delta variants, in contrast to what was observed at the beginning of the pandemic, no longer generate these defective genomes. Surprisingly, the process is repeated with Omicron, which at the beginning showed defective genomes again and its subvariants lose them.

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