The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants

Abstract 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...

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Main Authors: Carolina Campos, Sergi Colomer-Castell, Damir Garcia-Cehic, Josep Gregori, Cristina Andrés, Maria Piñana, Alejandra González-Sánchez, Blanca Borràs, Oleguer Parés-Badell, Caroline Melanie Adombi, Marta Ibañez-Lligoña, Juliana Esperalba, Maria Gema Codina, Ariadna Rando-Segura, Narcis Saubí, Juan Ignacio Esteban, Francisco Rodriguez-Frías, Tomàs Pumarola, Andrés Antón, Josep Quer
Format: Article
Language:English
Published: Nature Portfolio 2022-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-24918-8
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author Carolina Campos
Sergi Colomer-Castell
Damir Garcia-Cehic
Josep Gregori
Cristina Andrés
Maria Piñana
Alejandra González-Sánchez
Blanca Borràs
Oleguer Parés-Badell
Caroline Melanie Adombi
Marta Ibañez-Lligoña
Juliana Esperalba
Maria Gema Codina
Ariadna Rando-Segura
Narcis Saubí
Juan Ignacio Esteban
Francisco Rodriguez-Frías
Tomàs Pumarola
Andrés Antón
Josep Quer
author_facet Carolina Campos
Sergi Colomer-Castell
Damir Garcia-Cehic
Josep Gregori
Cristina Andrés
Maria Piñana
Alejandra González-Sánchez
Blanca Borràs
Oleguer Parés-Badell
Caroline Melanie Adombi
Marta Ibañez-Lligoña
Juliana Esperalba
Maria Gema Codina
Ariadna Rando-Segura
Narcis Saubí
Juan Ignacio Esteban
Francisco Rodriguez-Frías
Tomàs Pumarola
Andrés Antón
Josep Quer
author_sort Carolina Campos
collection DOAJ
description Abstract 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.
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spelling doaj.art-2f4e8323a97547f7a9f1ad86dee947682023-01-01T12:20:08ZengNature PortfolioScientific Reports2045-23222022-12-0112111110.1038/s41598-022-24918-8The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variantsCarolina Campos0Sergi Colomer-Castell1Damir Garcia-Cehic2Josep Gregori3Cristina Andrés4Maria Piñana5Alejandra González-Sánchez6Blanca Borràs7Oleguer Parés-Badell8Caroline Melanie Adombi9Marta Ibañez-Lligoña10Juliana Esperalba11Maria Gema Codina12Ariadna Rando-Segura13Narcis Saubí14Juan Ignacio Esteban15Francisco Rodriguez-Frías16Tomàs Pumarola17Andrés Antón18Josep Quer19Liver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariMicrobiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariMicrobiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariMicrobiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariPreventive Medicine, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariPreventive Medicine, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariMicrobiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariMicrobiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariMicrobiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariMicrobiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos IIIMicrobiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariMicrobiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariLiver Diseases-Viral Hepatitis, Liver Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariAbstract 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.https://doi.org/10.1038/s41598-022-24918-8
spellingShingle Carolina Campos
Sergi Colomer-Castell
Damir Garcia-Cehic
Josep Gregori
Cristina Andrés
Maria Piñana
Alejandra González-Sánchez
Blanca Borràs
Oleguer Parés-Badell
Caroline Melanie Adombi
Marta Ibañez-Lligoña
Juliana Esperalba
Maria Gema Codina
Ariadna Rando-Segura
Narcis Saubí
Juan Ignacio Esteban
Francisco Rodriguez-Frías
Tomàs Pumarola
Andrés Antón
Josep Quer
The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants
Scientific Reports
title The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants
title_full The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants
title_fullStr The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants
title_full_unstemmed The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants
title_short The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants
title_sort frequency of defective genomes in omicron differs from that of the alpha beta and delta variants
url https://doi.org/10.1038/s41598-022-24918-8
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