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Title

SARS-CoV-2 mutant spectra reveal differences between COVID-19 severity categories

AuthorsMartínez-González, Brenda; Soria, María Eugenia; Vázquez-Sirvent, Lucía; Ferrer-Orta, Cristina CSIC ; Lobo-Vega, Rebeca; Mínguez, Pablo; Fuente, Lorena de la; Llorens, Carlos; Soriano, Beatriz; Ramos-Ruíz, Ricardo; 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, Jordi; 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
Issue Date6-Sep-2022
CitationXVI Congreso Nacional de Virología (2022)
AbstractRNA 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.
DescriptionTrabajo presentado en el XVI Congreso Nacional de Virología, celebrado en Málaga (España) del 06 al 09 de septiembre de 2022.
URIhttp://hdl.handle.net/10261/281237
Appears in Collections:(IBMB) Comunicaciones congresos
(CBM) Comunicaciones congresos
(CNB) Comunicaciones congresos
(IPBLN) Comunicaciones congresos




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