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The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants Campos Martinez, Carolina Saubí Roca, Narcís Rodríguez Frias, Francisco Rando Segura, Ariadna Colomer-Castell, Sergi Garcia-Cehic, Damir Parés-Badell, Oleguer ADOMBI, Caroline Mélanie QUER, JOSEP Piñana, María González-Sánchez, Alejandra Esperalba, Juliana Codina, María Gema Pumarola Suñe, Tomàs Gregori Font, Josep Esteban Mur, Juan Ignacio BORRAS BERMEJO, BLANCA Ibañez Lligoña, Marta Antón Pagarolas, Andrés Andrés Vergés, Cristina Institut Català de la Salut [Campos C, Quer J] Grup de Recerca de les Malalties Hepàtiques, Unitat Hepàtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Colomer-Castell S] Grup de Recerca de les Malalties Hepàtiques, Unitat Hepàtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Garcia-Cehic D, Gregori J] Grup de Recerca de les Malalties Hepàtiques, Unitat Hepàtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. [ndrés C, Piñana M, González-Sánchez A, Esperalba J, Codina MG, Rando-Segura A, Saubí N] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Borràs B, Parés-Badell O] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Medicina Preventiva, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Adombi CM, Ibañez-Lligoña M] Grup de Recerca de les Malalties Hepàtiques, Unitat Hepàtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Esteban JI] Grup de Recerca de les Malalties Hepàtiques, Unitat Hepàtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Rodriguez-Frías F] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Bioquímica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pumarola T, Antón A] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Spain Vall d'Hebron Barcelona Hospital Campus COVID-19 (Malaltia) - Vacunació Immunoglobulines DISEASES::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections CHEMICALS AND DRUGS::Complex Mixtures::Biological Products::Vaccines::Viral Vaccines CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Neutralizing ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus COMPUESTOS QUÍMICOS Y DROGAS::mezclas complejas::productos biológicos::vacunas::vacunas víricas COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos neutralizantes Evolution; Genetics; Molecular biology Evolució; Genètica; Biologia molecular Evolución; Genética; Biología molecular The SARS-CoV-2 Omicron variant emerged showing higher transmissibility and possibly higher resistance to current COVID-19 vaccines than other variants dominating the global pandemic. In March 2020 we performed a study in clinical samples, where we found that a portion of genomes in the SARS-CoV-2 viral population accumulated deletions immediately before the S1/S2 cleavage site (furin-like cleavage site, PRRAR/S) of the spike gene, generating a frameshift and appearance of a premature stop codon. The main aim of this study was to determine the frequency of defective deletions in prevalent variants from the first to sixth pandemic waves in our setting and discuss whether the differences observed might support epidemiological proposals. The complete SARS-CoV-2 spike gene was deeply studied by next-generation sequencing using the MiSeq platform. More than 90 million reads were obtained from respiratory swab specimens of 78 COVID-19 patients with mild infection caused by the predominant variants circulating in the Barcelona city area during the six pandemic waves: B.1.5, B.1.1, B.1.177, Alpha, Beta, Delta, and Omicron. The frequency of defective genomes found in variants dominating the first and second waves was similar to that seen in Omicron, but differed from the frequencies seen in the Alpha, Beta and Delta variants. The changing pattern of mutations seen in the various SARS-CoV-2 variants driving the pandemic waves over time can affect viral transmission and immune escape. Here we discuss the putative biological effects of defective deletions naturally occurring before the S1/S2 cleavage site during adaption of the virus to human infection. This study was partially supported by Pla Estratègic de Recerca i Innovació en Salut (PERIS) – Direcció General de Recerca i Innovació en Salut (DGRIS), Catalan Health Ministry, Generalitat de Catalunya; the Spanish Network for the Research in Infectious Diseases (REIPI RD16/0016/0003) from the European Regional Development Fund (ERDF); Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297; Grant PI19/00301 from Instituto de Salud Carlos III cofinanced by the European Regional Development Fund (ERDF), and Gilead’s biomedical research project GLD21/00006. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiCov Database on which this research is based. 2023-02-01T12:55:58Z 2023-02-01T12:55:58Z 2022-12-29 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Campos C, Colomer-Castell S, Garcia-Cehic D, Gregori J, Andrés C, Piñana M, et al. The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants. Sci Rep. 2022 Dec 29;12:22571. 2045-2322 https://hdl.handle.net/11351/8945 10.1038/s41598-022-24918-8 36581627 eng Scientific Reports;12 https://doi.org/10.1038/s41598-022-24918-8 info:eu-repo/grantAgreement/ES/PE2013-2016/RD16%2F0016%2F0003 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Nature Portfolio Scientia