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5 results on '"Perales, Celia [0000-0003-1618-1937]"'

1. Puzzles, challenges, and information reservoir of SARS-CoV-2 quasispecies

Author

Ministerio de Ciencia e Innovación (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Instituto de Salud Carlos III, Fundació La Marató de TV3, Comunidad de Madrid, Fundación Ramón Areces, Fundación Banco Santander, Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Domingo, Esteban, Martínez-González, Brenda, García-Crespo, Carlos, Somovilla, Pilar, Ávila, Ana Isabel de, Soria, María Eugenia, Durán-Pastor, Antoni, Perales, Celia, Ministerio de Ciencia e Innovación (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Instituto de Salud Carlos III, Fundació La Marató de TV3, Comunidad de Madrid, Fundación Ramón Areces, Fundación Banco Santander, Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Domingo, Esteban, Martínez-González, Brenda, García-Crespo, Carlos, Somovilla, Pilar, Ávila, Ana Isabel de, Soria, María Eugenia, Durán-Pastor, Antoni, and Perales, Celia

Abstract

Upon the emergence of SARS-CoV-2 in the human population, it was conjectured that for this coronavirus the dynamic intra-host heterogeneity typical of RNA viruses would be toned down. Nothing of this sort is observed. Here we review the main observations on the complexity and diverse composition of SARS-CoV-2 mutant spectra sampled from infected patients, within the framework of quasispecies dynamics. The analyses suggest that the information provided by myriads of genomic sequences within infected individuals may have a predictive value of the genomic sequences that acquire epidemiological relevance. Possibilities to reconcile the presence of broad mutant spectra in the large RNA coronavirus genome with its encoding a 3' to 5' exonuclease proofreading-repair activity are considered. Indeterminations in the behavior of individual viral genomes provide a benefit for the survival of the ensemble. We propose that this concept falls in the domain of "stochastic thinking," a notion that applies also to cellular processes, as a means for biological systems to face unexpected needs.

Published
2023

2. SARS-CoV-2 Point Mutation and Deletion Spectra and Their Association with Different Disease Outcomes

Author

Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Esteban, Jaime [0000-0002-8971-3167], Verdaguer, Núria [0000-0001-8826-7129], Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Gallego, Isabel, Ávila, Ana Isabel de, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, Perales, Celia, Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Esteban, Jaime [0000-0002-8971-3167], Verdaguer, Núria [0000-0001-8826-7129], Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Gallego, Isabel, Ávila, Ana Isabel de, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, and Perales, Celia

Abstract

Mutant spectra of RNA viruses are important to understand viral pathogenesis and response to selective pressures. There is a need to characterize the complexity of mutant spectra in coronaviruses sampled from infected patients. In particular, the possible relationship between SARS-CoV-2 mutant spectrum complexity and disease associations has not been established. In the present study, we report an ultradeep sequencing (UDS) analysis of the mutant spectrum of amplicons from the nsp12 (polymerase)- and spike (S)-coding regions of 30 nasopharyngeal isolates (diagnostic samples) of SARS-CoV-2 of the first COVID-19 pandemic wave (Madrid, Spain, April 2020) classified according to the severity of ensuing COVID-19. Low-frequency mutations and deletions, counted relative to the consensus sequence of the corresponding isolate, were overwhelmingly abundant. We show that the average number of different point mutations, mutations per haplotype, and several diversity indices was significantly higher in SARS-CoV-2 isolated from patients who developed mild disease than in those associated with moderate or severe disease (exitus). No such bias was observed with RNA deletions. Location of amino acid substitutions in the three-dimensional structures of nsp12 (polymerase) and S suggest significant structural or functional effects. Thus, patients who develop mild symptoms may be a richer source of genetic variants of SARS-CoV-2 than patients with moderate or severe COVID-19.

Published
2022

3. SARS-CoV-2 Point Mutation and Deletion Spectra, and Their Association with Different Disease Outcome

Author

Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Fundació La Marató de TV3, Instituto de Salud Carlos III, Comunidad de Madrid, Fundación Ramón Areces, Banco Santander, Ministerio de Sanidad y Consumo (España), Ministerio de Economía y Competitividad (España), Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Esteban, Jaime [0000-0002-8971-3167], Verdaguer, Núria [0000-0001-8826-7129], Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Gallego, Isabel, Ávila, Ana Isabel de, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, Perales, Celia, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Fundació La Marató de TV3, Instituto de Salud Carlos III, Comunidad de Madrid, Fundación Ramón Areces, Banco Santander, Ministerio de Sanidad y Consumo (España), Ministerio de Economía y Competitividad (España), Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Esteban, Jaime [0000-0002-8971-3167], Verdaguer, Núria [0000-0001-8826-7129], Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Gallego, Isabel, Ávila, Ana Isabel de, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, and Perales, Celia

Abstract

Mutant spectra of RNA viruses are important to understand viral pathogenesis, and response to selective pressures. There is a need to characterize the complexity of mutant spectra in coronaviruses sampled from infected patients. In particular, the possible relationship between SARS-CoV-2 mutant spectrum complexity and disease associations has not been established. In the present study, we report an ultra-deep sequencing (UDS) analysis of the mutant spectrum of amplicons from the nsp12 (polymerase)- and spike (S)-coding regions of thirty nasopharyngeal isolates (diagnostic samples) of SARS-CoV-2 of the first COVID-19 pandemic wave (Madrid, Spain, April 2020) classified according to the severity of ensuing COVID-19. Low frequency mutations and deletions, counted relative to the consensus sequence of the corresponding isolate, were overwhelmingly abundant. We show that the average number of different point mutations, mutations per haplotype and several diversity indices was significantly higher in SARS-CoV-2 isolated from patients who developed mild disease than in those associated with moderate or severe disease (exitus). No such bias was observed with RNA deletions. Location of amino acid substitutions in the three dimensional structures of nsp12 (polymerase) and S suggest significant structural or functional effects. Thus, patients who develop mild symptoms may be a richer source of genetic variants of SARS-CoV-2 than patients with moderate or severe COVID-19.

Published
2022

4. High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Author

Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Banco Santander, Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Lobo-Vega, Rebeca [0000-0002-4882-6763], Perales, Celia [0000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, Perales, Celia, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Banco Santander, Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Lobo-Vega, Rebeca [0000-0002-4882-6763], Perales, Celia [0000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, and Perales, Celia

Abstract

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work is to determine a possible association between the viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we have clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or exitus. Here we report a statistically significant correlation between viral load and disease severity, being high viral load associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity, and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce the viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.

Published
2020

5. High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Author

Ignacio Gadea, Javier Ruiz-Hornillos, Rebeca Lobo-Vega, Jaime Esteban, Carmen Ayuso, A. Herrero, Marta Corton, Juan Carlos Taracido, Pablo Minguez, Ricardo Fernández-Roblas, Rosario López-Rodríguez, Ignacio Mahillo, María Eugenia Soria, Alicia Macías-Valcayo, Berta Almoguera, Lucía Vázquez-Sirvent, Brenda Martínez-González, Celia Perales, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Fundación Banco Santander, Agencia Estatal de Investigación (España), Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Cortón, Marta [0000-0003-0087-1626], Martínez-González, Brenda [0000-0002-4482-5181], Lobo-Vega, Rebeca [0000-0002-4882-6763], Vázquez-Sirvent, Lucía [0000-0002-0396-7781], Mínguez, Pablo [0000-0003-4099-9421], Macías-Valcayo, Alicia [0000-0003-3879-0493], Esteban, Jaime [0000-0002-8971-3167], Gadea, Ignacio [0000-0003-4684-7816], Ayuso, Carmen [0000-0002-9242-7065], Perales, Celia [000-0003-1618-1937], Banco Santander, Perales, Celia [0000-0003-1618-1937], Soria, María Eugenia, Lobo-Vega, Rebeca, Perales, Celia, Cortón, Marta, Martínez-González, Brenda, Vázquez-Sirvent, Lucía, Mínguez, Pablo, Macías-Valcayo, Alicia, Esteban, Jaime, Gadea, Ignacio, and Ayuso, Carmen

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, viruses, Population, Short Communications, Outbreak, COVID-19, Disease, medicine.disease, viral load, Risk factors, Diabetes mellitus, Intensive care, Internal medicine, Cohort, medicine, risk factors, General Materials Science, Viral load, education, business, Asthma
Abstract

Publisher's version disponible en: http://hdl.handle.net/10261/257116, COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work is to determine a possible association between the viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we have clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or exitus. Here we report a statistically significant correlation between viral load and disease severity, being high viral load associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity, and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce the viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression., This work was supported by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 Research Call COV20/00181) co-financed by European Development Regional Fund (A way to achieve Europe). The work was also supported by grants CSIC-COV19-014 from Consejo Superior de Investigaciones Cientificas (CSIC), BFU2017-91384-EXP from Ministerio de Ciencia, Innovacion y Universidades (MICIU), PI18/00210 from Instituto de Salud Carlos III. C.P., M.C. and P.M. are supported by the Miguel Servet program of the Instituto de Salud Carlos III (CPII19/00001, CPII17/00006 and CP16/00116, respectively) cofinanced by the European Regional Development Fund (ERDF). CIBERehd (Centro de Investigacion en Red de Enfermedades Hepaticas y Digestivas) is funded by Instituto de Salud Carlos III. Institutional grants from the Fundacion Ramon Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). B. M.-G. is supported by predoctoral contract PFIS FI19/00119 from Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo) cofinanced by Fondo Social Europeo (FSE). R. L.-V. is supported by predoctoral contract PEJD-2019-PRE/BMD-16414 from Comunidad de Madrid. R L-R is sponsored by the IIS-Fundacion Jimenez Diaz-UAM Genomic Medicine Chair.

Published
2021

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