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Título: | SARS-CoV-2 mutant spectra reveal differences between COVID-19 severity categories |
Autor: | Martínez-González, Brenda; Soria, María Eugenia; Vázquez-Sirvent, Lucía; Ferrer-Orta, Cristina CSIC ORCID ; Lobo-Vega, Rebeca; Mínguez, Pablo; Fuente, Lorena de la; Llorens, Carlos; Soriano, Beatriz; Ramos-Ruiz, Ricardo CSIC ORCID; Cortón, Marta; López-Rodríguez, Rosario; García-Crespo, Carlos; Somovilla, Pilar; Durán-Pastor, Antoni; Gallego, Isabel CSIC ORCID; Ávila, Ana Isabel de; Delgado, Soledad; Morán, Federico; López-Galíndez, Cecilio; Gómez-Castilla, Jordi CSIC ORCID; Enjuanes Sánchez, Luis CSIC ORCID ; Salar-Vidal, Llanos; Esteban-Muñoz, Mario; Esteban, Jaime; Fernández-Roblas, Ricardo; Gadea, Ignacio; Ayuso, Carmen; Ruíz-Hornillos, Javier; Verdaguer, Núria CSIC ORCID ; Domingo, Esteban CSIC ORCID; Perales, Celia CSIC ORCID | Fecha de publicación: | 6-sep-2022 | Citación: | XVI Congreso Nacional de Virología (2022) | Resumen: | RNA virus populations are composed of complex mixtures of genomes that are termed mutant spectra. SARS-CoV-2 replicates as a viral quasispecies, and mutations that are detected at low frequencies in a host can be dominant in subsequent variants. We have studied mutant spectrum complexities of SARS-CoV-2 populations derived from thirty nasopharyngeal swabs of patients infected during the first wave (April 2020) in the Hospital Universitario Fundación Jiménez Díaz. The patients were classified according to the COVID-19 severity in mild (non-hospitalized), moderate (hospitalized) and exitus (hospitalized with ICU admission and who passed away due to COVID-19). Using ultra-deep sequencing technologies (MiSeq, Illumina), we have examined four amplicons of the nsp12 (polymerase)-coding region and two amplicons of the spike-coding region. Ultra-deep sequencing data were analyzed with different cut-off frequency for mutation detection. Average number of different point mutations, mutations per haplotype and several diversity indices were significantly higher in SARS-CoV-2 isolated from patients who developed mild disease. A feature that we noted in the SARS-CoV-2 mutant spectra from diagnostic samples is the remarkable absence of mutations at intermediate frequencies, and an overwhelming abundance of mutations at frequencies lower than 10%. Thus, the decrease of the cut-off frequency for mutation detection from 0.5% to 0.1% revealed an increasement (50- to 100 fold) in the number of different mutations. The significantly higher frequency of mutations in virus from patients displaying mild than moderate or severe disease was maintained with the 0.1% cut- off frequency. To evaluate whether the frequency repertoire of amino acid substitutions differed between SARS-CoV-2 and the well characterized hepatitis C virus (HCV), we performed a comparative study of mutant spectra from infected patients using the same bioinformatics pipelines. HCV did not show the deficit of intermediate frequency substitutions that was observed with SARS-CoV-2. This difference was maintained when two functionally equivalent proteins, the corresponding viral polymerases, were compared. In conclusion, SARS-CoV-2 mutant spectra are rich reservoirs of mutants, whose complexity is not uniform among clinical isolates. Virus from patients who developed mild disease may be a source of new variants that may acquire epidemiological relevance. | Descripción: | Trabajo presentado en el XVI Congreso Nacional de Virología, celebrado en Málaga (España) del 06 al 09 de septiembre de 2022. | URI: | http://hdl.handle.net/10261/281237 |
Aparece en las colecciones: | (IBMB) Comunicaciones congresos (CBM) Comunicaciones congresos (CNB) Comunicaciones congresos (IPBLN) Comunicaciones congresos (PTI Salud Global) Colección Especial COVID-19 |
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