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Deep Sequencing Reveals Dual Evolution of SARS-CoV-2: Insights Into Defective Genomes From Wuhan-Hu-1 Variants to Omicron Subvariants.

Abstract

SARS-CoV-2 has evolved from early variants dominating the first (B.1.5, B.1.1) and second (B.1.177) pandemic waves, which exhibited a higher frequency of minority mutants with deletions leading to Defective Viral Genomes (DVGs) in the spike region near the S1/S2 cleavage site than the Alpha, Beta, and Delta variants. The emergence of Omicron has significantly altered the dominant variant profile, with Omicron subvariants now representing 100% of circulating viruses. To monitor the evolution and adaptation of Omicron in the human population, a deep-sequencing study was performed in RNA samples of BA.1, BA.1.1, BA.2, BA.5, BQ.1.1, XBB.1.5 and BA.2.86 Omicron subvariants. The findings reveal two occurrences of similar evolutionary patterns within SARS-CoV-2 characterized by a shift from a significant to a very low production of DVGs. This event suggests that DVGs might play a role in the virus's spread and adaptation for persistence in infected humans.

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Carolina Campos, Marta Ibañez-Lligoña, Sergi Colomer-Castell, Josep Gregori, Damir Garcia-Cehic, Cristina Andrés, Maria Piñana, Alejandra González-Sánchez, Ariadna Rando-Segura, Juliana Esperalba, Narcis Saubí, Maria Francesca Cortese, David Tabernero, Francisco Rodriguez-Frias, Roser Ferrer, Juan Ignacio Esteban, Renate W Kakze-van der Honing, Andries A Kampfraath, Júlia Vergara-Alert, Joaquim Segalés, Wim H M van der Poel, Tomàs Pumarola, Andrés Antón, Josep Quer. 2025. Deep Sequencing Reveals Dual Evolution of SARS-CoV-2: Insights Into Defective Genomes From Wuhan-Hu-1 Variants to Omicron Subvariants.. https://doi.org/10.1002/jmv.70476

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