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

Abstract

Omicron; Deep‐sequencing; Dual evolution

Òmicron; Seqüenciació profunda; Evolució dual

Ómicron; Secuenciación profunda; Evolución dual

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.

This study was supported by the Centro para el Desarrollo Tecnológico Industrial (CDTI) of the Spanish Ministry of Economy and Business, grant number IDI-20200297; Grant PID2021-126447OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by the ERDF A way of making Europe; Fondo de Investigación Sanitaria, Spanish Ministry of Economy and Competitiveness (grants FIS PI19/00301, PI19/00533, PI22/00258, PI22/00023, and PI23/01065); CIBER—Consorcio Centro de Investigación Biomédica en Red—(CIBERINFEC, ISCIII—CIBER of Infectious Diseases & CIBEREHD, ISCIII—CIBER of Hepatic and Digestive Diseases), Instituto de Salud Carlos III, Ministry of Science and Innovation and the European Union—NextGenerationEU. Research contributions of Wageningen Bioveterinary Research are funded from the ERRAZE (Early Response and Rapid Action Zoonotic Emergencies Program). C.C. received a predoctoral fellowship from the Vall d'Hebron Institute of Research (VHIR). M.I.-L. was supported by a fellowship from the “La Caixa” Foundation (ID 100010434), with code “LCF/BQ/DR23/12000020”. S.C-C. received support from the Spanish Ministry of Education grant FPU21/04150.