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

TL;DR

This study uses deep sequencing to track how SARS-CoV-2 evolved, showing a shift in defective genome production from early variants to Omicron subvariants.

Contribution

The study identifies dual evolutionary patterns in SARS-CoV-2 related to defective viral genome production.

Findings

Early variants had higher DVGs in the spike region near the S1/S2 cleavage site.

Omicron subvariants show a significant reduction in DVG production.

DVGs may influence the virus's spread and adaptation in humans.

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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