Author: "Jiménez Serrano, Santiago" - Searchworks@Jio Institute Digital Library Search Results

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1. Design and proof of concept of a double-panel TOF-PET system

Author: Gonzalez-Montoro, Andrea, Pavón, Noriel, Barberá, Julio, Cuarella, Neus, González, Antonio J., Jiménez-Serrano, Santiago, Lucero, Alejandro, Moliner, Laura, Sánchez, David, Vidal, Koldo, and Benlloch, José M.
Published: 2024
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2. Tracking SARS-CoV-2 introductions in Mozambique using pandemic-scale phylogenies: a retrospective observational study

Author: Martínez-Martínez, Francisco José, Massinga, Arsenia J, De Jesus, Áuria, Ernesto, Rita M, Cano-Jiménez, Pablo, Chiner-Oms, Álvaro, Gómez-Navarro, Inmaculada, Guillot-Fernández, Marina, Guinovart, Caterina, Sitoe, António, Vubil, Delfino, Bila, Rubão, Gujamo, Rufino, Enosse, Sónia, Jiménez-Serrano, Santiago, Torres-Puente, Manuela, Comas, Iñaki, Mandomando, Inácio, López, Mariana G, and Mayor, Alfredo
Published: 2023
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3. Atrial location optimization by electrical measures for Electrocardiographic Imaging

Author: Gisbert, Víctor, Jiménez-Serrano, Santiago, Roses-Albert, Eduardo, and Rodrigo, Miguel
Published: 2020
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4. First Results of the 4D-PET Brain System

Author: Gonzalez-Montoro, Andrea, primary, Jiménez-Serrano, Santiago, additional, Álamo, Jorge, additional, Barberá, Julio, additional, Lucero, Alejandro, additional, Cucarella, Neus, additional, Díaz, Karel, additional, Freire, Marta, additional, Gonzalez, Antonio J., additional, Moliner, Laura, additional, Mondejar, Álvaro, additional, Morera-Ballester, Constantino, additional, Prior, John, additional, Sánchez, David, additional, and Benlloch, Jose M., additional
Published: 2024
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5. Simulation Study of Clinical PET Scanners With Different Geometries, Including TOF and DOI Capabilities

Author: Cañizares, Gabriel, primary, Jiménez-Serrano, Santiago, additional, Lucero, Alejandro, additional, Morera-Ballester, Constantino, additional, Muñoz, Enrique, additional, Benlloch, José M., additional, and González, Antonio J., additional
Published: 2024
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6. Tracking SARS-CoV-2 introductions in Mozambique using pandemic-scale phylogenies: a retrospective observational study

Author: European Research Council, Bill & Melinda Gates Foundation, European Commission, Generalitat de Catalunya, Ministerio de Ciencia e Innovación (España), CSIC - Plataforma Temática Interdisciplinar del CSIC Salud Global (PTI Salud Global), Governo de Moçambique, Agencia Española de Cooperación Internacional para el Desarrollo, Comas, Iñaki [0000-0001-5504-9408], Martínez-Martínez, Francisco José, Massinga, Arsenia J, Jesus, Áuria De, Ernesto, Rita M., Cano-Jiménez, Pablo, Chiner-Oms, Álvaro, Gómez-Navarro, Inmaculada, Guillot-Fernández, Marina, Guinovart, Caterina, Sitoe, Antonio, Vubil, Delfino, Bila, Rubao, Gujamo, Rufino, Enosse, Sonia, Jiménez-Serrano, Santiago, Torres-Puente, Manuela, Comas, Iñaki, Mandomando, Inacio, López, Mariana G., Mayor, Alfredo, European Research Council, Bill & Melinda Gates Foundation, European Commission, Generalitat de Catalunya, Ministerio de Ciencia e Innovación (España), CSIC - Plataforma Temática Interdisciplinar del CSIC Salud Global (PTI Salud Global), Governo de Moçambique, Agencia Española de Cooperación Internacional para el Desarrollo, Comas, Iñaki [0000-0001-5504-9408], Martínez-Martínez, Francisco José, Massinga, Arsenia J, Jesus, Áuria De, Ernesto, Rita M., Cano-Jiménez, Pablo, Chiner-Oms, Álvaro, Gómez-Navarro, Inmaculada, Guillot-Fernández, Marina, Guinovart, Caterina, Sitoe, Antonio, Vubil, Delfino, Bila, Rubao, Gujamo, Rufino, Enosse, Sonia, Jiménez-Serrano, Santiago, Torres-Puente, Manuela, Comas, Iñaki, Mandomando, Inacio, López, Mariana G., and Mayor, Alfredo
Abstract: Background: From the start of the SARS-CoV-2 outbreak, global sequencing efforts have generated an unprecedented amount of genomic data. Nonetheless, unequal sampling between high-income and low-income countries hinders the implementation of genomic surveillance systems at the global and local level. Filling the knowledge gaps of genomic information and understanding pandemic dynamics in low-income countries is essential for public health decision making and to prepare for future pandemics. In this context, we aimed to discover the timing and origin of SARS-CoV-2 variant introductions in Mozambique, taking advantage of pandemic-scale phylogenies. Methods: We did a retrospective, observational study in southern Mozambique. Patients from Manhiça presenting with respiratory symptoms were recruited, and those enrolled in clinical trials were excluded. Data were included from three sources: (1) a prospective hospital-based surveillance study (MozCOVID), recruiting patients living in Manhiça, attending the Manhiça district hospital, and fulfilling the criteria of suspected COVID-19 case according to WHO; (2) symptomatic and asymptomatic individuals with SARS-CoV-2 infection recruited by the National Surveillance system; and (3) sequences from SARS-CoV-2-infected Mozambican cases deposited on the Global Initiative on Sharing Avian Influenza Data database. Positive samples amenable for sequencing were analysed. We used Ultrafast Sample placement on Existing tRees to understand the dynamics of beta and delta waves, using available genomic data. This tool can reconstruct a phylogeny with millions of sequences by efficient sample placement in a tree. We reconstructed a phylogeny (~7·6 million sequences) adding new and publicly available beta and delta sequences. Findings: A total of 5793 patients were recruited between Nov 1, 2020, and Aug 31, 2021. During this time, 133 328 COVID-19 cases were reported in Mozambique. 280 good quality new SARS-CoV-2 sequences were obtained aft
Published: 2023

7. Evolutionary and phenotypic characterization of spike mutations in a new SARS-CoV-2 Lineage reveals two Variants of Interest

Author: Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, European Commission, Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Frances-Gomez, Clara [0000-0001-7341-3824], Chiner-Oms, Álvaro [0000-0002-0463-0101], López, Mariana G. [0000-0002-2216-9232], Jiménez Serrano, Santiago [0000-0003-2917-6053], Cancino-Muñoz, Irving [0000-0002-5261-1634], Ruiz-Hueso, Paula [0000-0003-0217-471X], Torres-Puente, Manuela [0000-0002-8352-180X], D’Auria, Giuseppe [0000-0003-0672-2541], Martínez-Priego, Llucia [0000-0002-1073-269X], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Marina, Alberto [0000-0002-1334-5273], Geller, Ron [0000-0002-7612-4611], Coscolla, Mireia [0000-0003-0752-0538], Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez-Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, Bracho, María Alma, D’Auria, Giuseppe, Martínez-Priego, Llucia, Guerreiro, Manuel, Montero-Alonso, Marta, Gómez, María Dolores, Piñana, José Luis, Seqcovid-Spain Consortium, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, Coscollá, Mireia, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, European Commission, Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Frances-Gomez, Clara [0000-0001-7341-3824], Chiner-Oms, Álvaro [0000-0002-0463-0101], López, Mariana G. [0000-0002-2216-9232], Jiménez Serrano, Santiago [0000-0003-2917-6053], Cancino-Muñoz, Irving [0000-0002-5261-1634], Ruiz-Hueso, Paula [0000-0003-0217-471X], Torres-Puente, Manuela [0000-0002-8352-180X], D’Auria, Giuseppe [0000-0003-0672-2541], Martínez-Priego, Llucia [0000-0002-1073-269X], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Marina, Alberto [0000-0002-1334-5273], Geller, Ron [0000-0002-7612-4611], Coscolla, Mireia [0000-0003-0752-0538], Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez-Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, Bracho, María Alma, D’Auria, Giuseppe, Martínez-Priego, Llucia, Guerreiro, Manuel, Montero-Alonso, Marta, Gómez, María Dolores, Piñana, José Luis, Seqcovid-Spain Consortium, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, and Coscollá, Mireia
Abstract: Molecular epidemiology of SARS-CoV-2 aims to monitor the appearance of new variants with the potential to change the virulence or transmissibility of the virus. During the first year of SARS-CoV-2 evolution, numerous variants with possible public health impact have emerged. We have detected two mutations in the Spike protein at amino acid positions 1163 and 1167 that have appeared independently multiple times in different genetic backgrounds, indicating they may increase viral fitness. Interestingly, the majority of these sequences appear in transmission clusters, with the genotype encoding mutations at both positions increasing in frequency more than single-site mutants. This genetic outcome that we denote as Lineage B.1.177.637, belongs to clade 20E and includes 12 additional single nucleotide polymorphisms but no deletions with respect to the reference genome (first sequence in Wuhan). B.1.177.637 appeared after the first wave of the epidemic in Spain, and subsequently spread to eight additional countries, increasing in frequency among sequences in public databases. Positions 1163 and 1167 of the Spike protein are situated in the HR2 domain, which is implicated in the fusion of the host and viral membranes. To better understand the effect of these mutations on the virus, we examined whether B.1.177.637 altered infectivity, thermal stability, or antibody sensitivity. Unexpectedly, we observed reduced infectivity of this variant relative to the ancestral 20E variant in vitro while the levels of viral RNA in nasopharyngeal swabs did not vary significantly. In addition, we found the mutations do not impact thermal stability or antibody susceptibility in vaccinated individuals but display a moderate reduction in sensitivity to neutralization by convalescent sera from early stages of the pandemic. Altogether, this lineage could be considered a Variant of Interest (VOI), we denote VOI1163.7. Finally, we detected a sub-cluster of sequences within VOI1163.7 that have acqu
Published: 2021

8. Evolutionary and Phenotypic Characterization of Two Spike Mutations in European Lineage 20E of SARS-CoV-2

Author: Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, European Commission, Marina, Alberto [0000-0002-1334-5273], Comas, Iñaki [0000-0001-5504-9408], Chiner-Oms, Álvaro [0000-0002-0463-0101], López, Mariana G. [0000-0002-2216-9232], Jiménez Serrano, Santiago [0000-0003-2917-6053], Cancino-Muñoz, Irving [0000-0002-5261-1634], Torres-Puente, Manuela [0000-0002-8352-180X], Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez-Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, Bracho, María Alma, D’Auria, Giuseppe, Martínez-Priego, Llucia, Guerreiro, Manuel, Montero-Alonso, Marta, Gómez, María Dolores, Piñana, José Luis, Seqcovid-Spain Consortium, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, Coscollá, Mireia, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, European Commission, Marina, Alberto [0000-0002-1334-5273], Comas, Iñaki [0000-0001-5504-9408], Chiner-Oms, Álvaro [0000-0002-0463-0101], López, Mariana G. [0000-0002-2216-9232], Jiménez Serrano, Santiago [0000-0003-2917-6053], Cancino-Muñoz, Irving [0000-0002-5261-1634], Torres-Puente, Manuela [0000-0002-8352-180X], Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez-Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, Bracho, María Alma, D’Auria, Giuseppe, Martínez-Priego, Llucia, Guerreiro, Manuel, Montero-Alonso, Marta, Gómez, María Dolores, Piñana, José Luis, Seqcovid-Spain Consortium, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, and Coscollá, Mireia
Abstract: We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence in vitro, and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutralization by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multiple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investigated was consistent with the lack of advantage observed in the clinical and experimental data. IMPORTANCE We observed repeated, independent emergence of mutations in the SARS-CoV-2 spike involving amino acids 1163 and 1167, within the HR2 functional motif. Conclusions derived from evolutionary and genomic diversity analysis suggest that the co-occurrence of both mutations might pose an advantage for the virus and therefore a threat to effective control of the epidemic. However, biological characterization, including in vitro experiments and analysis of clinical data, indicated no clear benefit in terms of stability or infectivity. In agreement with this, continuous epidemiologi
Published: 2021

9. The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant

Author: Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, European Commission, Generalitat Valenciana, Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], D'Auria, Giuseppe [0000-0003-0672-2541], Gómez-Navarro, Inmaculada [0000-0002-5235-7365], Jiménez Serrano, Santiago [0000-0003-2917-6053], Aranzamendi Zaldumbide, Maitane [0000-0003-2432-7078], Boga, José Antonio [0000-0002-5500-9972], Bordoy, Antoni E. [0000-0002-1165-542X], Costa-Alcalde, José J. [0000-0002-1916-2216], Toro Peinado, Inmaculada de [0000-0002-8151-3275], López-Causapé, Carla [0000-0003-2228-2005], Martín, Vicente [0000-0003-0552-2804], Moreno-Muñoz, Rosario [0000-0002-0185-5612], Parra Grande, Mónica [0000-0002-8330-7467], Balaguer, María Dolores [0000-0003-3808-7300], Coscolla, Mireia [0000-0003-0752-0538], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], López, Mariana G., Chiner-Oms, Álvaro, García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D'Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Alberola, Juan, Albert, Eliseo, Aranzamendi Zaldumbide, Maitane, Bea-Escudero, María Pilar, Boga, José Antonio, Bordoy, Antoni E., Canut, Andrés, Carvajal, Ana, Cilla Eguiluz, Gustavo, Cordón Rodríguez, María Luz, Costa-Alcalde, José J., Toro, María de, Toro Peinado, Inmaculada de, Pozo, José Luis del, Duchêne, Sebastián, Fernández-Pinero, Jovita, Fuster Escrivá, Begoña, Gimeno, Concepción, González Galán, Verónica, Gonzalo Jimeno, Nieves, Hernáez Crespo, Silvia, Herranz, Marta, Lepe, José A., López-Causapé, Carla, López-Hontangas, José Luis, Martín, Vicente, Martró, Elisa, Milagro Beamonte, Ana, Montes Ros, Milagrosa, Moreno-Muñoz, Rosario, Navarro, David, Navarro-Marí, José María, Not, Anna, Oliver, Antonio, Palop-Borrás, Begoña, Parra Grande, Mónica, Pedrosa-Corral, Irene, Pérez González, María Carmen, Pérez-Lago, Laura, Pérez-Ruiz, Mercedes, Piñeiro Vázquez, Luis, Rabella, Nuria, Rezusta, Antonio, Robles Fonseca, Lorena, Rodríguez-Villodres, Ángel, Sanbonmatsu-Gámez, Sara, Sicilia, Jon, Soriano, Álex, Balaguer, María Dolores, Torres, Ignacio, Tristancho, Alexander, Marimón, José María, Seqcovid-Spain Consortium, Coscollá, Mireia, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, European Commission, Generalitat Valenciana, Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], D'Auria, Giuseppe [0000-0003-0672-2541], Gómez-Navarro, Inmaculada [0000-0002-5235-7365], Jiménez Serrano, Santiago [0000-0003-2917-6053], Aranzamendi Zaldumbide, Maitane [0000-0003-2432-7078], Boga, José Antonio [0000-0002-5500-9972], Bordoy, Antoni E. [0000-0002-1165-542X], Costa-Alcalde, José J. [0000-0002-1916-2216], Toro Peinado, Inmaculada de [0000-0002-8151-3275], López-Causapé, Carla [0000-0003-2228-2005], Martín, Vicente [0000-0003-0552-2804], Moreno-Muñoz, Rosario [0000-0002-0185-5612], Parra Grande, Mónica [0000-0002-8330-7467], Balaguer, María Dolores [0000-0003-3808-7300], Coscolla, Mireia [0000-0003-0752-0538], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], López, Mariana G., Chiner-Oms, Álvaro, García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D'Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Alberola, Juan, Albert, Eliseo, Aranzamendi Zaldumbide, Maitane, Bea-Escudero, María Pilar, Boga, José Antonio, Bordoy, Antoni E., Canut, Andrés, Carvajal, Ana, Cilla Eguiluz, Gustavo, Cordón Rodríguez, María Luz, Costa-Alcalde, José J., Toro, María de, Toro Peinado, Inmaculada de, Pozo, José Luis del, Duchêne, Sebastián, Fernández-Pinero, Jovita, Fuster Escrivá, Begoña, Gimeno, Concepción, González Galán, Verónica, Gonzalo Jimeno, Nieves, Hernáez Crespo, Silvia, Herranz, Marta, Lepe, José A., López-Causapé, Carla, López-Hontangas, José Luis, Martín, Vicente, Martró, Elisa, Milagro Beamonte, Ana, Montes Ros, Milagrosa, Moreno-Muñoz, Rosario, Navarro, David, Navarro-Marí, José María, Not, Anna, Oliver, Antonio, Palop-Borrás, Begoña, Parra Grande, Mónica, Pedrosa-Corral, Irene, Pérez González, María Carmen, Pérez-Lago, Laura, Pérez-Ruiz, Mercedes, Piñeiro Vázquez, Luis, Rabella, Nuria, Rezusta, Antonio, Robles Fonseca, Lorena, Rodríguez-Villodres, Ángel, Sanbonmatsu-Gámez, Sara, Sicilia, Jon, Soriano, Álex, Balaguer, María Dolores, Torres, Ignacio, Tristancho, Alexander, Marimón, José María, Seqcovid-Spain Consortium, Coscollá, Mireia, González-Candelas, Fernando, and Comas, Iñaki
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.
Published: 2021

10. Evolutionary and phenotypic characterization of spike mutations in a new SARS-CoV-2 Lineage reveals two Variants of Interest

Author: Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, Bracho, María Alma, D’Auria, Giuseppe, Martínez-Priego, Llucia, Guerreiro, Manuel, Montero-Alonso, Marta, Gómez, María Dolores, Piñana, José Luis, Seqcovid-Spain Consortium, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, Coscollá, Mireia, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, European Commission, Ruiz-Rodríguez, Paula, Frances-Gomez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, D’Auria, Giuseppe, Martínez-Priego, Llucia, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, Coscolla, Mireia, Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Frances-Gomez, Clara [0000-0001-7341-3824], Chiner-Oms, Álvaro [0000-0002-0463-0101], López, Mariana G. [0000-0002-2216-9232], Jiménez Serrano, Santiago [0000-0003-2917-6053], Cancino-Muñoz, Irving [0000-0002-5261-1634], Ruiz-Hueso, Paula [0000-0003-0217-471X], Torres-Puente, Manuela [0000-0002-8352-180X], D’Auria, Giuseppe [0000-0003-0672-2541], Martínez-Priego, Llucia [0000-0002-1073-269X], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Marina, Alberto [0000-0002-1334-5273], Geller, Ron [0000-0002-7612-4611], and Coscolla, Mireia [0000-0003-0752-0538]
Subjects: 2019-20 coronavirus outbreak, Lineage (genetic), Geography, Research council, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), European Regional Development Fund, media_common.cataloged_instance, Spike (database), European union, Valencian community, Genealogy, media_common
Abstract: Molecular epidemiology of SARS-CoV-2 aims to monitor the appearance of new variants with the potential to change the virulence or transmissibility of the virus. During the first year of SARS-CoV-2 evolution, numerous variants with possible public health impact have emerged. We have detected two mutations in the Spike protein at amino acid positions 1163 and 1167 that have appeared independently multiple times in different genetic backgrounds, indicating they may increase viral fitness. Interestingly, the majority of these sequences appear in transmission clusters, with the genotype encoding mutations at both positions increasing in frequency more than single-site mutants. This genetic outcome that we denote as Lineage B.1.177.637, belongs to clade 20E and includes 12 additional single nucleotide polymorphisms but no deletions with respect to the reference genome (first sequence in Wuhan). B.1.177.637 appeared after the first wave of the epidemic in Spain, and subsequently spread to eight additional countries, increasing in frequency among sequences in public databases. Positions 1163 and 1167 of the Spike protein are situated in the HR2 domain, which is implicated in the fusion of the host and viral membranes. To better understand the effect of these mutations on the virus, we examined whether B.1.177.637 altered infectivity, thermal stability, or antibody sensitivity. Unexpectedly, we observed reduced infectivity of this variant relative to the ancestral 20E variant in vitro while the levels of viral RNA in nasopharyngeal swabs did not vary significantly. In addition, we found the mutations do not impact thermal stability or antibody susceptibility in vaccinated individuals but display a moderate reduction in sensitivity to neutralization by convalescent sera from early stages of the pandemic. Altogether, this lineage could be considered a Variant of Interest (VOI), we denote VOI1163.7. Finally, we detected a sub-cluster of sequences within VOI1163.7 that have acquired two additional changes previously associated with antibody escape and it could be identified as VOI1163.7.V2. Overall, we have detected the spread of a new Spike variant that may be advantageous to the virus and whose continuous transmission poses risks by the acquisition of additional mutations that could affect pre-existing immunity., This work was funded by the Instituto de Salud Carlos III project COV20/00140 and COV20/00437, Spanish National Research Council project CSIC-COV19-021 and CSIC-COVID19-082, and the Generalitat Valenciana (SEJI/2019/011 and Covid_19-SCI). Action co-financed by the European Union through the Operational Program of the European Regional Development Fund (ERDF) of the Valencian Community 2014-2020. M.C. and R.G. are supported by Ramon y Cajal program from Ministerio de Ciencia.
Published: 2021
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11. The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant

Author: López, Mariana G., Chiner-Oms, Álvaro, García de Viedma, Darío, Ruiz-Rodriguez, Paula, Bracho, Maria Alma, Cancino-Muñoz, Irving, D’Auria, Giuseppe, de Marco, Griselda, García-González, Neris, Goig, Galo Adrian, Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Martinez-Priego, Llúcia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Alberola, Juan, Albert, Eliseo, Aranzamendi Zaldumbide, Maitane, Bea-Escudero, María Pilar, Boga, Jose Antonio, Bordoy, Antoni E., Canut-Blasco, Andrés, Carvajal, Ana, Cilla Eguiluz, Gustavo, Cordón Rodríguez, Maria Luz, Costa-Alcalde, José J., de Toro, María, de Toro Peinado, Inmaculada, del Pozo, Jose Luis, Duchêne, Sebastián, Fernández-Pinero, Jovita, Fuster Escrivá, Begoña, Gimeno Cardona, Concepción, González Galán, Verónica, Gonzalo Jiménez, Nieves, Hernáez Crespo, Silvia, Herranz, Marta, Lepe, José Antonio, López-Causapé, Carla, López-Hontangas, José Luis, Martín, Vicente, Martró, Elisa, Milagro Beamonte, Ana, Montes Ros, Milagrosa, Moreno-Muñoz, Rosario, Navarro, David, Navarro-Marí, José María, Not, Anna, Oliver, Antonio, Palop-Borrás, Begoña, Parra Grande, Mónica, Pedrosa-Corral, Irene, Pérez González, Maria Carmen, Pérez-Lago, Laura, Pérez-Ruiz, Mercedes, Piñeiro Vázquez, Luis, Rabella, Nuria, Rezusta, Antonio, Robles Fonseca, Lorena, Rodríguez-Villodres, Ángel, Sanbonmatsu-Gámez, Sara, Sicilia, Jon, Soriano, Alex, Tirado Balaguer, María Dolores, Torres, Ignacio, Tristancho, Alexander, Marimón, José María, Pérez-Tur, Jordi, Catalán-Alonso, Pilar, Suárez González, Julia, Muñoz, Patricia, Ruiz-Rodríguez, Paula, Bracho, María Alma, Martínez Priego, Llúcia, Galán-Vendrell, Inmaculada, De Marco, Griselda, Ferrús-Abad, María Loreto, Carbó-Ramírez, Sandra, Nogueira, Jose Miguel, Camarena, Juan José, Martínez Expósito, Óscar, Antona Urieta, Nerea, Castelló-Abietar, Cristian, Rojo-Alba, Susana, Álvarez-Argüelles, Marta Elena, Melón, Santiago, Antuori, Adrián, Fernández-Navarro, Anabel, Lecaroz Agara, Maria Concepción, Gómez-González, Carmen, Aguirre-Quiñonero, Amaia, López-Mirones, José Israel, Fernández-Torres, Marina, Almela-Ferrer, Maria Rosario, Fregeneda-Grandes, Juan Miguel, Argüello, Héctor, Sorarrain, Ane, Trastoy, Rocío, Barbeito Castiñeiras, Gema, Coira, Amparo, Pérez del Molino, María Luisa, Aguilera, Antonio, Mediavilla Gradolph, Maria Concepción, Fernández-Alonso, Mirian, González-Recio, Oscar, Gutiérrez-Rivas, Mónica, Jiménez Clavero, Miguel Ángel, Ocete Mochón, María Dolores, Medina-Gonzalez, Rafael, Reina, Jordi, Gómez-Ruiz, Maria Dolores, Gonzalez-Barbera, Eva M., Molina, Antonio J., Fernandez-Villa, Tania, Martínez-Cameo, Nieves Felisa, Gracia-Grataloup, Yolanda, Tirado Balaguer, Maria Dolores, Gómez Alonso, Bárbara, Arjona Zaragozí, Francisco José, Chamizo López, Francisco Javier, Bordes-Benítez, Ana, Rabella, Núria, Navarro, Ferran, Miró, Elisenda, Simarro Córdoba, Encarnación, Lozano-Serra, Julia, Soriano, Álex, Roig Sena, Francisco Javier, Vanaclocha Luna, Hermelinda, Sanmartín, Isabel, García-Souto, Daniel, Pequeño-Valtierra, Ana, Tubio, Jose M. C., Temes, Javier, Rodríguez-Castro, Jorge, Santamarina García, Martín, Rodríguez-Iglesias, Manuel, Galán-Sanchez, Fátima, Rodríguez-Pallares, Salud, Azcona-Gutiérrez, José Manuel, Blasco-Alberdi, Miriam, Mayor, Alfredo, García-Basteiro, Alberto L., Moncunill, Gemma, Dobaño, Carlota, Cisteró, Pau, Mitjà, Oriol, González-Beiras, Camila, Vall-Mayans, Martí, Corbacho-Monné, Marc, Alemany, Andrea, Muñoz-Cuevas, Cristina, Rodríguez-Rodríguez, Guadalupe, Benito, Rafael, Algarate, Sonia, Bueno, Jessica, Vergara-Gómez, Andrea, Martínez, Miguel J., Vila, Jordi, Rubio, Elisa, Peiró-Mestres, Aida, Navero-Castillejos, Jessica, Posada, David, Valverde, Diana, Estévez, Nuria, Fernández-Silva, Iria, de Chiara, Loretta, Gallego-García, Pilar, Varela, Nair, Gómez-Pinedo, Ulises, Gozalo-Margüello, Mónica, Cano García, Maria Eliecer, Méndez-Legaza, José Manuel, Rodríguez-Lozano, Jesus, Siller, María, Pablo-Marcos, Daniel, Ruiz-García, Maria Montserrat, Galiana, Antonio, Sánchez-Almendro, Judith, Gascón Ros, Maria Isabel, Torregrosa-Hetland, Cristina Juana, Pastor Boix, Eva María, Cascales Ramos, Paloma, Garcinuño Enríquez, Pedro Luis, Raga Borja, Salvador, González Cantó, Julia, Martínez Macias, Olalla, de Salazar, Adolfo, Viñuela González, Laura, Chueca, Natalia, García, Federico, Gómez-Camarasa, Cristina, Farga Martí, Amparo, Falcón, Rocío, Domínguez-Márquez, Victoria, Planas, Anna M., Fernández-Cádenas, Israel, Marcos, Maria Ángeles, Ezpeleta, Carmen, Navascués, Ana, Miqueleiz Zapatero, Ana, Segovia, Manuel, Moreno-Docón, Antonio, Viedma, Esther, Recio Martínez, Raúl, Muñoz-Gallego, Irene, Gonzalez-Bodi, Sara, Folgueira, Maria Dolores, Mingorance, Jesús, Dahdouh, Elias, Lázaro-Perona, Fernando, Rodríguez-Tejedor, María, Romero-Gómez, María Pilar, García-Rodríguez, Julio, Galán, Juan Carlos, Rodríguez-Dominguez, Mario, Martínez-García, Laura, Abreu Di Berardino, Melanie, Ponce-Alonso, Manuel, González-Alba, Jose Maria, Sanz-Muñoz, Ivan, Pérez San José, Diana, Gil Fortuño, Maria, Bellido-Blasco, Juan B., Yagüe Muñoz, Alberto, Hernández Pérez, Noelia, Buj Jordá, Helena, Pérez Olaso, Óscar, González Praetorius, Alejandro, Martínez Ramírez, Nora Mariela, Ramírez Marinero, Aida, Padilla León, Eduardo, Vilas Basil, Alba, Canal Aranda, Mireia, Bernet Sánchez, Albert, Bellés Bellés, Alba, López González, Eric, Prats Sánchez, Iván, García-González, Mercè, Martínez-Lirola, Miguel José, Rodríguez Maresca, Manuel Ángel, Cabezas Fernández, Maria Teresa, Carrillo Gil, María Eugenia, Ventero Martín, Maria Paz, Molina Pardines, Carmen, Orta Mira, Nieves, Navarro Cots, María, Vidal Catalá, Inmaculada, García Nava, Isabel, Illescas Fernández-Bermejo, Soledad, Martínez-Alarcón, José, Torres-Narbona, Marta, Colmenarejo, Cristina, García-Agudo, Lidia, Pérez García, Jorge A., Yago López, Martín, Goberna Bravo, María Ángeles, Simón García, Victoria, Llop Furquet, Gonzalo, Iranzo Tatay, Agustín, Moreno-Marro, Sandra, Lozano Rodríguez, Noelia, Broseta Tamarit, Amparo, Badiola Díez, Juan José, Martínez-Ramírez, Amparo, Dopazo, Ana, Callejas, Sergio, Benguría, Alberto, Aguado, Begoña, Alcamí, Antonio, Bermejo Bermejo, Marta, Ramos-Ruíz, Ricardo, Fernández Soria, Víctor Manuel, Simón Soria, Fernando, Roig Cardells, Mercedes, Coscolla, Mireia, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, European Commission, Generalitat Valenciana, Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], D'Auria, Giuseppe [0000-0003-0672-2541], Gómez-Navarro, Inmaculada [0000-0002-5235-7365], Jiménez Serrano, Santiago [0000-0003-2917-6053], Aranzamendi Zaldumbide, Maitane [0000-0003-2432-7078], Boga, José Antonio [0000-0002-5500-9972], Bordoy, Antoni E. [0000-0002-1165-542X], Costa-Alcalde, José J. [0000-0002-1916-2216], Toro Peinado, Inmaculada de [0000-0002-8151-3275], López-Causapé, Carla [0000-0003-2228-2005], Martín, Vicente [0000-0003-0552-2804], Moreno-Muñoz, Rosario [0000-0002-0185-5612], Parra Grande, Mónica [0000-0002-8330-7467], Balaguer, María Dolores [0000-0003-3808-7300], Coscolla, Mireia [0000-0003-0752-0538], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Ministerio de Ciencia (España), Generalitat Valenciana (España), Chiner-Oms, Álvaro, Ruiz-Rodríguez, Paula, D'Auria, Giuseppe, Gómez-Navarro, Inmaculada, Jiménez Serrano, Santiago, Aranzamendi Zaldumbide, Maitane, Boga, José Antonio, Bordoy, Antoni E., Costa-Alcalde, José J., Toro Peinado, Inmaculada de, López-Causapé, Carla, Martín, Vicente, Moreno-Muñoz, Rosario, Parra Grande, Mónica, Balaguer, María Dolores, Coscolla, Mireia, González-Candelas, Fernando, Comas, Iñaki, and Marimon, Jose Maria
Subjects: DYNAMICS, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Physical Distancing, Biology, Severity of Illness Index, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Pandemic, Quarantine, Genetics, Humans, Clade, Phylogeny, 030304 developmental biology, 0303 health sciences, Models, Statistical, SARS-CoV-2, Incidence (epidemiology), Incidence, Genetic variants, COVID-19, Genomics, New variant, Dynamics, Virus, 3. Good health, Spain, Communicable Disease Control, VIRUS, 030217 neurology & neurosurgery, Demography
Abstract: SeqCOVID-Spain consortium: Álvaro Chiner-Oms, Irving Cancino-Muñoz, Mariana G. López, Manuela Torres-Puente, Inmaculada Gómez-Navarro, Santiago Jiménez-Serrano, Jordi Pérez-Tur, Darío García de Viedma, Laura Pérez-Lago, Marta Herranz, Jon Sicilia, Pilar Catalán-Alonso, Julia Suárez González, Patricia Muñoz, Mireia Coscolla, Paula Ruiz-Rodríguez, Fernando González-Candelas, Iñaki Comas, Lidia Ruiz-Roldán, María Alma Bracho, Neris García-González, Llúcia Martínez Priego, Inmaculada Galán-Vendrell, Paula Ruiz-Hueso, Griselda De Marco, María Loreto Ferrús-Abad, Sandra Carbó-Ramírez, Giuseppe D’Auria, Galo Adrian Goig, Juan Alberola, Jose Miguel Nogueira, Juan José Camarena, David Navarro, Eliseo Albert, Ignacio Torres, Maitane Aranzamendi Zaldumbide, Óscar Martínez Expósito, Nerea Antona Urieta, María de Toro, María Pilar Bea-Escudero, Jose Antonio Boga, Cristian Castelló-Abietar, Susana Rojo-Alba, Marta Elena Álvarez-Argüelles, Santiago Melón, Elisa Martró, Antoni E. Bordoy, Anna Not, Adrián Antuori, Anabel Fernández-Navarro, Andrés Canut-Blasco, Silvia Hernáez Crespo, Maria Luz Cordón Rodríguez, Maria Concepción Lecaroz Agara, Carmen Gómez-González, Amaia Aguirre-Quiñonero, José Israel López-Mirones, Marina Fernández-Torres, Maria Rosario Almela-Ferrer, Ana Carvajal, Juan Miguel Fregeneda-Grandes, Héctor Argüello, Gustavo Cilla Eguiluz, Milagrosa Montes Ros, Luis Piñeiro Vázquez, Ane Sorarrain, José María Marimón, José J. Costa-Alcalde, Rocío Trastoy, Gema Barbeito Castiñeiras, Amparo Coira, María Luisa Pérez del Molino, Antonio Aguilera, Begoña Palop-Borrás, Inmaculada de Toro Peinado, Maria Concepción Mediavilla Gradolph, Mercedes Pérez-Ruiz, Mirian Fernández-Alonso, Jose Luis del Pozo, Oscar González-Recio, Mónica Gutiérrez-Rivas, Jovita Fernández-Pinero, Miguel Ángel Jiménez Clavero, Begoña Fuster Escrivá, Concepción Gimeno Cardona, María Dolores Ocete Mochón, Rafael Medina-Gonzalez, José Antonio Lepe, Verónica González Galán, Ángel Rodríguez-Villodres, Nieves Gonzalo Jiménez, Jordi Reina, Carla López-Causapé, Maria Dolores Gómez-Ruiz, Eva M. Gonzalez-Barbera, José Luis López-Hontangas, Vicente Martín, Antonio J. Molina, Tania Fernandez-Villa, Ana Milagro Beamonte, Nieves Felisa Martínez-Cameo, Yolanda Gracia-Grataloup, Rosario Moreno-Muñoz, Maria Dolores Tirado Balaguer, José María Navarro-Marí, Irene Pedrosa-Corral, Sara Sanbonmatsu-Gámez, Antonio Oliver, Mónica Parra Grande, Bárbara Gómez Alonso, Francisco José Arjona Zaragozí, Maria Carmen Pérez González, Francisco Javier Chamizo López, Ana Bordes-Benítez, Núria Rabella, Ferran Navarro, Elisenda Miró, Antonio Rezusta, Alexander Tristancho, Encarnación Simarro Córdoba, Julia Lozano-Serra, Lorena Robles Fonseca, Álex Soriano, Francisco Javier Roig Sena, Hermelinda Vanaclocha Luna, Isabel Sanmartín, Daniel García-Souto, Ana Pequeño-Valtierra, Jose M. C. Tubio, Javier Temes, Jorge Rodríguez-Castro, Martín Santamarina García, Manuel Rodríguez-Iglesias, Fátima Galán-Sanchez, Salud Rodríguez-Pallares, José Manuel Azcona-Gutiérrez, Miriam Blasco-Alberdi, Alfredo Mayor, Alberto L. García-Basteiro, Gemma Moncunill, Carlota Dobaño, Pau Cisteró, Oriol Mitjà, Camila González-Beiras, Martí Vall-Mayans, Marc Corbacho-Monné, Andrea Alemany, Cristina Muñoz-Cuevas, Guadalupe Rodríguez-Rodríguez, Rafael Benito, Sonia Algarate, Jessica Bueno, Andrea Vergara-Gómez, Miguel J. Martínez, Jordi Vila, Elisa Rubio, Aida Peiró-Mestres, Jessica Navero-Castillejos, David Posada, Diana Valverde, Nuria Estévez, Iria Fernández-Silva, Loretta de Chiara, Pilar Gallego-García, Nair Varela, Ulises Gómez-Pinedo, Mónica Gozalo-Margüello, Maria Eliecer Cano García, José Manuel Méndez-Legaza, Jesus Rodríguez-Lozano, María Siller, Daniel Pablo-Marcos, Maria Montserrat Ruiz-García, Antonio Galiana, Judith Sánchez-Almendro, Maria Isabel Gascón Ros, Cristina Juana Torregrosa-Hetland, Eva María Pastor Boix, Paloma Cascales Ramos, Pedro Luis Garcinuño Enríquez, Salvador Raga Borja, Julia González Cantó, Olalla Martínez Macias, Adolfo de Salazar, Laura Viñuela González, Natalia Chueca, Federico García, Cristina Gómez-Camarasa, Amparo Farga Martí, Rocío Falcón, Victoria Domínguez-Márquez, Anna M. Planas, Israel Fernández-Cádenas, Maria Ángeles Marcos, Carmen Ezpeleta, Ana Navascués, Ana Miqueleiz Zapatero, Manuel Segovia, Antonio Moreno-Docón, Esther Viedma, Raúl Recio Martínez, Irene Muñoz-Gallego, Sara Gonzalez-Bodi, Maria Dolores Folgueira, Jesús Mingorance, Elias Dahdouh, Fernando Lázaro-Perona, María Rodríguez-Tejedor, María Pilar Romero-Gómez, Julio García-Rodríguez, Juan Carlos Galán, Mario Rodríguez-Dominguez, Laura Martínez-García, Melanie Abreu Di Berardino, Manuel Ponce-Alonso, Jose Maria González-Alba, Ivan Sanz-Muñoz, Diana Pérez San José, Maria Gil Fortuño, Juan B. Bellido-Blasco, Alberto Yagüe Muñoz, Noelia Hernández Pérez, Helena Buj Jordá, Óscar Pérez Olaso, Alejandro González Praetorius, Nora Mariela Martínez Ramírez, Aida Ramírez Marinero, Eduardo Padilla León, Alba Vilas Basil, Mireia Canal Aranda, Albert Bernet Sánchez, Alba Bellés Bellés, Eric López González, Iván Prats Sánchez, Mercè García-González, Miguel José Martínez-Lirola, Manuel Ángel Rodríguez Maresca, Maria Teresa Cabezas Fernández, María Eugenia Carrillo Gil, Maria Paz Ventero Martín, Carmen Molina Pardines, Nieves Orta Mira, María Navarro Cots, Inmaculada Vidal Catalá, Isabel García Nava, Soledad Illescas Fernández-Bermejo, José Martínez-Alarcón, Marta Torres-Narbona, Cristina Colmenarejo, Lidia García-Agudo, Jorge A. Pérez García, Martín Yago López, María Ángeles Goberna Bravo, Victoria Simón García, Gonzalo Llop Furquet, Agustín Iranzo Tatay, Sandra Moreno-Marro, Noelia Lozano Rodríguez, Amparo Broseta Tamarit, Juan José Badiola Díez, Amparo Martínez-Ramírez, Ana Dopazo, Sergio Callejas, Alberto Benguría, Begoña Aguado, Antonio Alcamí, Marta Bermejo Bermejo, Ricardo Ramos-Ruíz, Víctor Manuel Fernández Soria, Fernando Simón Soria & Mercedes Roig Cardells, The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re, This work was mainly funded by the Instituto de Salud Carlos III project COV20/00140, with additional funding by Spanish National Research Council project CSIC-COV19-021, Ministerio de Ciencia project PID2019-104477RB-100, ERC StG 638553 and ERC CoG 101001038 to I.C., and BFU2017-89594R to F.G.C. M.C. is supported by Ramón y Cajal program from Ministerio de Ciencia and grants RTI2018-094399-A-I00 and Generalitat Valenciana (Regional Government) project SEJI/2019/011. We gratefully acknowledge Hospital Universitari Vall d’Hebron, Instituto de Salud Carlos III, IrsiCaixa AIDS Research Lab and all the international researchers and institutions that submitted sequenced SARS-CoV-2 genomes to the GISAID’s EpiCov Database (Supplementary Table 1), as an important part of our analyses has been made possible by the sharing of their work. We also thank Unidad de Bioinformática y Estadística, Centro de Investigación Príncipe Felipe, for allowing us to use the Computer Cluster to perform some of the bioinformatic analysis.
Published: 2021

12. From 12 to 1 ECG lead: multiple cardiac condition detection mixing a hybrid machine learning approach with a one-versus-rest classification strategy

Author: Jiménez-Serrano, Santiago, primary, Rodrigo, Miguel, additional, Calvo, Conrado J, additional, Millet, José, additional, and Castells, Francisco, additional
Published: 2022
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13. Co-evolution of the SARS-CoV-2 genome and sequencing approaches in the PTI+ Global Health Genomic Surveillance Platform

Author: Cano-Jiménez, Pablo, Torres-Puente, Manuela, Cancino-Muñoz, Irving, Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Chiner-Oms, Álvaro, Inal, Göktuğ, Comas, Iñaki, Cano-Jiménez, Pablo, Torres-Puente, Manuela, Cancino-Muñoz, Irving, Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Chiner-Oms, Álvaro, Inal, Göktuğ, and Comas, Iñaki
Published: 2022

14. A Genomic Snapshot of the SARS-CoV-2 Pandemic in the Balearic Islands

Author: Instituto de Salud Carlos III, European Research Council, Comas, Iñaki [0000-0001-5504-9408], López-Causapé, Carla, Fraile-Ribot, Pablo A., Jiménez-Serrano, Santiago, Cabot, Gabriel, Barrio-Tofiño, Ester del, Prado, M. Carmen, Linares, Juana María, López, Aranzazu, Hurtado, Adoración, Riera, Elena, Serra, Antoni, Roselló, Eva, Carbó, Lluis, Fernández-Baca, Victoria, Gallegos, Carmen, Saurina, Juan, Arteaga, Emilio, Salom, M. Magdalena, Salvá, Antonia, Nicolau, Antoni, González-Candelas, Fernando, Comas, Iñaki, Oliver, Antonio, Instituto de Salud Carlos III, European Research Council, Comas, Iñaki [0000-0001-5504-9408], López-Causapé, Carla, Fraile-Ribot, Pablo A., Jiménez-Serrano, Santiago, Cabot, Gabriel, Barrio-Tofiño, Ester del, Prado, M. Carmen, Linares, Juana María, López, Aranzazu, Hurtado, Adoración, Riera, Elena, Serra, Antoni, Roselló, Eva, Carbó, Lluis, Fernández-Baca, Victoria, Gallegos, Carmen, Saurina, Juan, Arteaga, Emilio, Salom, M. Magdalena, Salvá, Antonia, Nicolau, Antoni, González-Candelas, Fernando, Comas, Iñaki, and Oliver, Antonio
Abstract: Objective: To analyze the SARS-CoV-2 genomic epidemiology in the Balearic Islands, a unique setting in which the course of the pandemic has been influenced by a complex interplay between insularity, severe social restrictions and tourism travels. Methods: Since the onset of the pandemic, more than 2,700 SARS-CoV-2 positive respiratory samples have been randomly selected and sequenced in the Balearic Islands. Genetic diversity of circulating variants was assessed by lineage assignment of consensus whole genome sequences with PANGOLIN and investigation of additional spike mutations. Results: Consensus sequences were assigned to 46 different PANGO lineages and 75% of genomes were classified within a VOC, VUI, or VUM variant according to the WHO definitions. Highest genetic diversity was documented in the island of Majorca (42 different lineages detected). Globally, lineages B.1.1.7 and B.1.617.2/AY.X were identified as the 2 major lineages circulating in the Balearic Islands during the pandemic, distantly followed by lineages B.1.177/B.1.177.X. However, in Ibiza/Formentera lineage distribution was slightly different and lineage B.1.221 was the third most prevalent. Temporal distribution analysis showed that B.1 and B.1.5 lineages dominated the first epidemic wave, lineage B.1.177 dominated the second and third, and lineage B.1.617.2 the fourth. Of note, lineage B.1.1.7 became the most prevalent circulating lineage during first half of 2021; however, it was not associated with an increased in COVID-19 cases likely due to severe social restrictions and limited travels. Additional spike mutations were rarely documented with the exception of mutation S:Q613H which has been detected in several genomes (n = 25) since July 2021. Conclusion: Virus evolution, mainly driven by the acquisition and selection of spike substitutions conferring biological advantages, social restrictions, and size population are apparently key factors for explaining the epidemic patterns registered in
Published: 2022

15. Co-evolution of the SARS-CoV-2 genome and sequencing approaches in the PTI+ Global Health Genomic Surveillance Platform

Author: Cano Jiménez, Pablo, Torres-Puente, Manuela, Cancino-Muñoz, Irving, Gómez-Navarro, Inmaculada, Jiménez Serrano, Santiago, Chiner-Oms, Álvaro, Inal, Göktuğ, and Comas, Iñaki
Abstract: Resumen del póster presentado a las II Jornadas Científicas PTI + Salud Global, celebradas los días 5 y 6 de octubre de 2022 en el Auditorio Santiago Grisolía de Valencia (España).
Published: 2022

16. A Genomic Snapshot of the SARS-CoV-2 Pandemic in the Balearic Islands

Author: López-Causapé, Carla, primary, Fraile-Ribot, Pablo A., additional, Jiménez-Serrano, Santiago, additional, Cabot, Gabriel, additional, del Barrio-Tofiño, Ester, additional, Prado, M. Carmen, additional, Linares, Juana María, additional, López, Aranzazu, additional, Hurtado, Adoración, additional, Riera, Elena, additional, Serra, Antoni, additional, Roselló, Eva, additional, Carbó, Lluis, additional, Fernández-Baca, M. Victoria, additional, Gallegos, Carmen, additional, Saurina, Juan, additional, Arteaga, Emilio, additional, Salom, M. Magdalena, additional, Salvá, Antonia, additional, Nicolau, Antoni, additional, González-Candelas, Fernando, additional, Comas, Iñaki, additional, and Oliver, Antonio, additional
Published: 2022
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17. Genomic Surveillance of SARS-CoV-2 in Mozambique Using Pandemic-Scale Phylogenies

Author: Martínez-Martínez, Francisco José, primary, Massinga, Arsenia J., additional, De Jesus, Áuria, additional, Ernesto, Rita M., additional, Cano-Jiménez, Pablo, additional, Chiner-Oms, Álvaro, additional, Gómez-Navarro, Inmaculada, additional, Guillot-Fernández, Marina, additional, Guinovart, Caterina, additional, Sitoe, Antonio, additional, Vubil, Delfino, additional, Bila, Rubão, additional, Gujamo, Rufino, additional, Viegas, Sofia, additional, Ismael, Nalia, additional, Jiménez-Serrano, Santiago, additional, Enosse, Sónia, additional, Torres-Puente, Manuela, additional, Comas, Iñaki, additional, Mandomando, Inacio, additional, López, Mariana G., additional, and Mayor, Alfredo, additional
Published: 2022
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18. Multiple Cardiac Disease Detection from Minimal-Lead ECG Combining Feedforward Neural Networks with a One-vs-Rest Approach

Author: Jiménez-Serrano, Santiago, RODRIGO BORT, MIGUEL, Calvo Saiz, Conrado Javier, Castells, Francisco, and Millet Roig, José
Subjects: TECNOLOGIA ELECTRONICA
Abstract: [EN] Although standard 12-lead ECG is the primary technique in cardiac diagnostic, detecting different cardiac diseases using single or reduced number of leads is still challenging. The purpose of our team, itaca-UPV, is to provide a method able to classify ECG records using minimal lead information in the context of the 2021 PhysioNet/Computing in Cardiology Challenge, also using only a single-lead. We resampled and filtered the ECG signals, and extracted 109 features mostly based on Hearth Rhythm Variability (HRV). Then, we used selected features to train one feed-forward neural network (FFNN) with one hidden layer for each class using a One-vs-Rest approach, thus allowing each ECG to be classified as belonging to none or more than one class. Finally, we performed a 3-fold cross validation to assess the model performance. Our classifiers received scores of 0.34, 0.34, 0.27, 0.30, and 0.34 (ranked 26th, 21th, 29th, 25th, and 22th out of 39 teams) for the 12, 6, 4, 3 and 2-lead versions of the hidden test set with the Challenge evaluation metric. Our minimal-lead approach may be beneficial for novel portable or wearable ECG devices used as screening tools, as it can also detect multiple and concurrent cardiac conditions. Accuracy in detection can be improved adding more disease-specific features.
Published: 2021
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19. Evolution, virulence and immunogenicity of relevant SARS-CoV-2 spike mutants

Author: Coscollá, Mireia, Ruiz-Rodríguez, Paula, Francés-Cuesta, Carlos, Geller, Ron, Chiner-Oms, Álvaro, Jiménez Serrano, Santiago, Marina, Alberto, Martínez-Priego, Llucia, D'Auria, Giuseppe, López, Mariana G., Cancino-Muñoz, Irving, Torres-Puente, Manuela, Bracho, María Alma, Ruiz-Hueso, Paula, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki, Chiner-Oms, Álvaro, Comas, Iñaki [0000-0001-5504-9408], and Chiner-Oms, Álvaro [0000-0002-0463-0101]
Abstract: SeqCOVm-SPAIN consortium., Trabajo presentado al 31st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), celebrado online del 9 al 12 de julio de 2021., We have detected two mutations in the Spike protein of SARS-CoV-2 sequences at amino acid positions 1163 and 1167 which appeared independently in multiple transmission clusters and different genetic backgrounds, indicating they may increase viral fitness. Both mutations appeared together in a cluster within clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information of the S protein in the preand post-fusion conformations we predict that both mutations confer rigidity, that potentially could decrease viral fitness. Despite the multiple and successful appearance of two HR2 mutations during the first year of SARS-CoV-2 evolution, in vi tro stability, infectivi ty, or antibody escape does not seem to play a role., This work was funded by the Instituto de Salud Carlos III project COV2o/o0140 and COV2o/o0437• Spanish National Research Council project CSIC"COV19~021 and CSIC-COVID19-082, and the Generalitat Valenciana (SEJI/2019/011 and Covid 19-SCI).Action co-financed by the European Union through the Operational Program of the European Regional Development Fund (ERDF) ofthe Valencian Community 2014-2020. MC is supported by Ramón y Caja/program from Ministerio de Ciencia, grant RTI2018-094399-A-Joo.
Published: 2021

20. Complete Analysis of the Epidemiological Scenario around a SARS-CoV-2 Reinfection: Previous Infection Events and Subsequent Transmission

Author: Pérez Lago, Laura, primary, Pérez Latorre, Leire, additional, Herranz, Marta, additional, Tejerina, Francisco, additional, Sola-Campoy, Pedro J., additional, Sicilia, Jon, additional, Suárez-González, Julia, additional, Andrés-Zayas, Cristina, additional, Chiner-Oms, Alvaro, additional, Jiménez-Serrano, Santiago, additional, García-González, Neris, additional, Comas, Iñaki, additional, González-Candelas, Fernando, additional, Martínez-Laperche, Carolina, additional, Catalán, Pilar, additional, Muñoz, Patricia, additional, and García de Viedma, Darío, additional
Published: 2021
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21. The SeqCOVID-Spain consortium: unravelling the dynamics of the COVID-19 first epidemic wave in Spain

Author: Chiner-Oms, Álvaro, López, Mariana G., García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D’Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Coscollá, Mireia, González-Candelas, Fernando, Comas, Iñaki, Seqcovid-Spain Consortium, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), European Research Council, Comas, Iñaki [0000-0001-5504-9408], and Comas, Iñaki
Abstract: Póster presentado a la Applied Bioinformatics and Public Health Microbiology 2021 Virtual Conference, celebrada del 5 al 7 de mayo de 2021., The COVID-19 pandemic has shaken the world since the beginning of 2020. Spain is among the European countries with the highest incidence of the disease during the first pandemic wave. We established a multidisciplinary consortium to monitor and study the evolution of the epidemic, with the aim of contributing to decision making and stopping rapid spreading across the country. We present the results for 2170 sequences from the first wave of the SARS-Cov-2 epidemic in Spain, representing 12% of diagnosed cases until 14th March. This effort allows us to document at least 500 initialintroductions, between early February-March from multiple international sources. Importantly, we document the early raise of two dominant genetic variants in Spain (Spanish Epidemic Clades), named SEC7 and SEC8, likely amplified by superspreading events. In sharp contrast to other non Asian countries those two variants were closely related to the initial variants of SARS-CoV-2 described in Asia and represented 40% of the genome sequences analyzed. The two dominant SECs were widely spread across the country compared to other genetic variants with SEC8 reaching a 60% prevalence just before the lockdown. Employing Bayesian phylodynamic analysis, we inferred a reduction in the effective reproductive number of these two SECs from around 2.5 to below 0.5 after the implementation of strict public-health interventions in mid-March. The effects of lockdown on the genetic variants of the virus are reflected in the general replacement of pre-existing SECs by a new variant at the beginning of the summer season. Our results reveal a significant difference in the genetic makeup of the epidemic in Spain and support the effectiveness of lockdown measures in controlling virus spread even for the most successful genetic variants., This work was funded by the Instituto de Salud Carlos III project COV20/00140, Spanish National Research Council project CSIC-COV19-021, Ministerio de Ciencia PID2019-104477RB-I00 and ERC StG 638553 to IC, and BFU2017-89594R to FGC. MC is supported by Ramón y Cajal program from Ministerio de Ciencia and grants RTI2018-094399-A-I00 and SEJI/2019/011.
Published: 2021

22. Emergence of adaptive mutations of the spike In SARS-CoV-2

Author: Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, Jiménez Serrano, Santiago, Bracho, María Alma, D'Auria, Giuseppe, González-Candelas, Fernando, Geller, Ron, Comas, Iñaki, and Seqcovid-Spain Consortium
Abstract: Resumen del trabajo presentado al II Congreso Nacional Covid-19, celebrado de forma virtual del 12 al 16 de abril de 2021., Surveillance of mutants of SARS-CoV-2 aims to monitor the appearance of new variants that could potentially change the biological properties of the virus. During the first year of SARS-CoV-2 evolution, different variants have been detected with different degrees of biological impact on the virus and also on the epidemic. We have detected two mutations of the spike protein of SARS-CoV-2 that have appeared independently multiple times in different genetic backgrounds and hosts, possibly indicating they could increase viral fitness. Interestingly, when both mutations appeared together, the genotype increased in frequency more than the individual mutants. This variant that we call Variant of Interest 1 and includes 12 other single nucleotide polymorphisms but no deletions with respect to the reference genome. VOI.1 appeared after the First epidemic Wave in Spain, and subsequently migrated and increased in frequency in 8 countries. VOI.1 includes a cluster of sequences that have acquired the concerning mutation E484K, which could result in antibody escape. We explored if these two mutations confer a greater capacity to the virus to produce more particles. Unexpectedly, we find a reduction in infectivity of this variant versus the 20EU1 in two different cell lines. However, clinical results differ slightly and we found that individuals infected with VOI.1 have similar levels of viral RNA in nasopharyngeal swabs than patients infected with 20EU1 variants, both of them significantly higher than non 20EU1 lineages. Finally, in order to assess the risk of VOI.1 because of antibody escape, we explored the impact on immunogenicity. A moderate but significant reduction in sensitivity to neutralization by sera from convalescent donors obtained from the early period of the pandemic was observed. Overall we could detect and monitor the spread of a variant of interest which could pose a potential risk. The expansion of such variants has allowed the acquisition of another potentially risky mutation, present in other variants of concern, which could pose an additional threat.
Published: 2021

23. Genomic determinants associated with SARS-CoV-2 virulence

Author: Ruiz-Rodríguez, Paula, Chaturvedi, N., Bracho, María Alma, Chiner-Oms, Álvaro, Jiménez Serrano, Santiago, López, Mariana G., Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, D’auria, M., Martínez-Priego, Llucia, González-Candelas, Fernando, Comas, Iñaki, Coscollá, Mireia, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Torres-Puente, Manuela [0000-0002-8352-180X], López, Mariana G. [0000-0002-2216-9232], Chiner-Oms, Álvaro [0000-0002-0463-0101], Comas, Iñaki, Torres-Puente, Manuela, López, Mariana G., and Chiner-Oms, Álvaro
Abstract: Trabajo presentado al 31st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), celebrado online del 9 al 12 de julio de 2021., This work was funded by the Instituto de Salud Carlos III project COV2o/oo140 and COV2o/ o0437,Spanish National Research Council project CSIC COV19·0l1 and CSIC-COVID19-082,and the Generalitat Valenciana (SEJI/2019/011 and Covid_19-SCI).Action co-financed by the European Union through the Operatianal Program of the European Regional Development Fund (ERDF) of the Valencian Community 2014-2020.MC is supported by Ramón y Cajal program from Ministerio de Ciencia,grant RTI2018-094399-A-I00.
Published: 2021

24. Genomic determinants associated with SARS-CoV-2 virulence

Author: Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Torres-Puente, Manuela [0000-0002-8352-180X], López, Mariana G. [0000-0002-2216-9232], Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula, Chaturvedi, N., Bracho, María Alma, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, López, Mariana G., Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, D’auria, M., Martínez-Priego, Llucia, González-Candelas, Fernando, Comas, Iñaki, Coscollá, Mireia, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Torres-Puente, Manuela [0000-0002-8352-180X], López, Mariana G. [0000-0002-2216-9232], Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula, Chaturvedi, N., Bracho, María Alma, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, López, Mariana G., Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, D’auria, M., Martínez-Priego, Llucia, González-Candelas, Fernando, Comas, Iñaki, and Coscollá, Mireia
Published: 2021

25. Evolution, virulence and immunogenicity of relevant SARS-CoV-2 spike mutants

Author: Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Chiner-Oms, Álvaro [0000-0002-0463-0101], Coscollá, Mireia, Ruiz-Rodríguez, Paula, Francés-Cuesta, Carlos, Geller, Ron, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, Marina, Alberto, Martínez-Priego, Llucia, D'Auria, Giuseppe, López, Mariana G., Cancino-Muñoz, Irving, Torres-Puente, Manuela, Bracho, María Alma, Ruiz-Hueso, Paula, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Chiner-Oms, Álvaro [0000-0002-0463-0101], Coscollá, Mireia, Ruiz-Rodríguez, Paula, Francés-Cuesta, Carlos, Geller, Ron, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, Marina, Alberto, Martínez-Priego, Llucia, D'Auria, Giuseppe, López, Mariana G., Cancino-Muñoz, Irving, Torres-Puente, Manuela, Bracho, María Alma, Ruiz-Hueso, Paula, González-Candelas, Fernando, and Comas, Iñaki
Abstract: We have detected two mutations in the Spike protein of SARS-CoV-2 sequences at amino acid positions 1163 and 1167 which appeared independently in multiple transmission clusters and different genetic backgrounds, indicating they may increase viral fitness. Both mutations appeared together in a cluster within clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information of the S protein in the preand post-fusion conformations we predict that both mutations confer rigidity, that potentially could decrease viral fitness. Despite the multiple and successful appearance of two HR2 mutations during the first year of SARS-CoV-2 evolution, in vi tro stability, infectivi ty, or antibody escape does not seem to play a role.
Published: 2021

26. The SeqCOVID-Spain consortium: unravelling the dynamics of the COVID-19 first epidemic wave in Spain

Author: Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), European Research Council, Comas, Iñaki [0000-0001-5504-9408], Chiner-Oms, Álvaro, López, Mariana G., García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D’Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Coscollá, Mireia, González-Candelas, Fernando, Comas, Iñaki, Seqcovid-Spain Consortium, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), European Research Council, Comas, Iñaki [0000-0001-5504-9408], Chiner-Oms, Álvaro, López, Mariana G., García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D’Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Coscollá, Mireia, González-Candelas, Fernando, Comas, Iñaki, and Seqcovid-Spain Consortium
Abstract: The COVID-19 pandemic has shaken the world since the beginning of 2020. Spain is among the European countries with the highest incidence of the disease during the first pandemic wave. We established a multidisciplinary consortium to monitor and study the evolution of the epidemic, with the aim of contributing to decision making and stopping rapid spreading across the country. We present the results for 2170 sequences from the first wave of the SARS-Cov-2 epidemic in Spain, representing 12% of diagnosed cases until 14th March. This effort allows us to document at least 500 initialintroductions, between early February-March from multiple international sources. Importantly, we document the early raise of two dominant genetic variants in Spain (Spanish Epidemic Clades), named SEC7 and SEC8, likely amplified by superspreading events. In sharp contrast to other non Asian countries those two variants were closely related to the initial variants of SARS-CoV-2 described in Asia and represented 40% of the genome sequences analyzed. The two dominant SECs were widely spread across the country compared to other genetic variants with SEC8 reaching a 60% prevalence just before the lockdown. Employing Bayesian phylodynamic analysis, we inferred a reduction in the effective reproductive number of these two SECs from around 2.5 to below 0.5 after the implementation of strict public-health interventions in mid-March. The effects of lockdown on the genetic variants of the virus are reflected in the general replacement of pre-existing SECs by a new variant at the beginning of the summer season. Our results reveal a significant difference in the genetic makeup of the epidemic in Spain and support the effectiveness of lockdown measures in controlling virus spread even for the most successful genetic variants.
Published: 2021

27. Complete analysis of the epidemiological scenario around a SARS-CoV-2 reinfection: previous infection events and subsequent transmission

Author: Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Pérez-Lago, Laura, Pérez Latorre, Leire, Herranz, Marta, Tejerina, Francisco, Sola-Campoy, Pedro J., Sicilia, Jon, Suárez-González, Julia, Andrés-Zayas, Cristina, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, García-González, Neris, Comas, Iñaki, González-Candelas, Fernando, Martínez-Laperche, Carolina, Catalán, Pilar, Muñoz, Patricia, García de Viedma, Darío, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Pérez-Lago, Laura, Pérez Latorre, Leire, Herranz, Marta, Tejerina, Francisco, Sola-Campoy, Pedro J., Sicilia, Jon, Suárez-González, Julia, Andrés-Zayas, Cristina, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, García-González, Neris, Comas, Iñaki, González-Candelas, Fernando, Martínez-Laperche, Carolina, Catalán, Pilar, Muñoz, Patricia, and García de Viedma, Darío
Abstract: The first descriptions of reinfection by SARS-CoV-2 have been recently reported. However, these studies focus exclusively on the reinfected case, without considering the epidemiological context of the event. We present the first complete analysis of the epidemiological scenario around a reinfection by SARS-CoV-2, including three cases preceding the reinfection, the reinfected case per se, and the subsequent transmission to another seven cases. Our analysis is supported by host genetics, viral whole genome sequencing, phylogenomic population analysis, and refined epidemiological data obtained from in-depth interviews with the involved subjects. The reinfection involved a 53-year-old woman with asthma, with a first COVID-19 episode in April 2020 and a much more severe second episode four months and a half later, with COVID-19 seroconversion in August, and requiring hospital admission.
Published: 2021

28. Complete analysis of the epidemiological scenario around a SARS-CoV-2 reinfection: previous infection events and subsequent transmission

Author: Pérez Lago, Laura, Pérez Latorre, Leire, Herranz, Marta, Tejerina, Francisco, Sola-Campoy, Pedro J., Sicilia, Jon, Suárez-González, Julia, Andrés-Zayas, Cristina, Chiner-Oms, Álvaro, Jiménez Serrano, Santiago, García-González, Neris, Comas, Iñaki, González-Candelas, Fernando, Martínez-Laperche, Carolina, Catalán, Pilar, Muñoz, Patricia, García de Viedma, Darío, Gregorio Marañón Microbiology-ID COVID 19 Study Group, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Comas, Iñaki, González-Candelas, Fernando, Comas, Iñaki [0000-0001-5504-9408], and González-Candelas, Fernando [0000-0002-0879-5798]
Subjects: Male, medicine.medical_specialty, Pediatrics, Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Context (language use), Microbiology, Severity of Illness Index, reinfection, Medicine, Humans, Transmission, Family, Seroconversion, education, Molecular Biology, Phylogeny, First episode, education.field_of_study, Whole Genome Sequencing, business.industry, Transmission (medicine), SARS-CoV-2, transmission, COVID-19, Genomics, Middle Aged, QR1-502, Spain, Reinfection, Female, Contact Tracing, business, Contact tracing, Research Article
Abstract: 9 páginas, 3 figuras. The data that support the findings of this study (Fastq files) are publicly available. Fastq files above the GISAID thresholds were deposited at GISAID (hCoV-19/Spain/MD-IBV-99007733/2020, hCoV-19/Spain/MD-IBV-99007151/2020, hCoV-19/Spain/MD-IBV-99007734/2020, and hCoV-19/Spain/MDIBV-99007170/2020). All sequences were also deposited at the ENA (European Nucleotide Archive; https:// www.ebi.ac.uk/ena/browser/home) (ERR5698024, ERR5697187, ERR6459974, ERR5698025, and ERR5697254)., The first descriptions of reinfection by SARS-CoV-2 have been recently reported. However, these studies focus exclusively on the reinfected case, without considering the epidemiological context of the event. Our objectives were to perform a complete analysis of the sequential infections and community transmission events around a SARS-CoV-2 reinfection, including the infection events preceding it, the exposure, and subsequent transmissions. Our analysis was supported by host genetics, viral whole-genome sequencing, phylogenomic viral population analysis, and refined epidemiological data obtained from interviews with the involved subjects. The reinfection involved a 53-year-old woman with asthma (Case A), with a first COVID-19 episode in April 2020 and a much more severe second episode 4-1/2 months later, with SARS-CoV-2 seroconversion in August, that required hospital admission. An extended genomic analysis allowed us to demonstrate that the strain involved in Case A's reinfection was circulating in the epidemiological context of Case A and was also transmitted subsequently from Case A to her family context. The reinfection was also supported by a phylogenetic analysis, including 348 strains from Madrid, which revealed that the strain involved in the reinfection was circulating by the time Case A suffered the second episode, August-September 2020, but absent at the time range corresponding to Case A's first episode. IMPORTANCE We present the first complete analysis of the epidemiological scenario around a reinfection by SARS-CoV-2, more severe than the first episode, including three cases preceding the reinfection, the reinfected case per se, and the subsequent transmission to another seven cases., This work was supported by Instituto de Salud Carlos III (Ref COV20/00140: SeqCOVID - Consorcio para la epidemiología genómica de SARS-CoV-2 en España) and by Consejo Superior de Investigaciones Científicas (CSIC) (PTI Salud Global), Miguel Servet contract CP15/00075, to L.P.L.
Published: 2020

29. Atrial location optimization by electrical measures for Electrocardiographic Imaging

Author: Universitat Politècnica de València. Instituto Universitario de Aplicaciones de las Tecnologías de la Información - Institut Universitari d'Aplicacions de les Tecnologies de la Informació, Universitat Politècnica de València. Departamento de Sistemas Informáticos y Computación - Departament de Sistemes Informàtics i Computació, Universitat Politècnica de València. Departamento de Estadística e Investigación Operativa Aplicadas y Calidad - Departament d'Estadística i Investigació Operativa Aplicades i Qualitat, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Nvidia, Generalitat Valenciana, Gisbert Soler, Víctor, Jiménez-Serrano, Santiago, Roses-Albert, Eduardo, RODRIGO BORT, MIGUEL, Universitat Politècnica de València. Instituto Universitario de Aplicaciones de las Tecnologías de la Información - Institut Universitari d'Aplicacions de les Tecnologies de la Informació, Universitat Politècnica de València. Departamento de Sistemas Informáticos y Computación - Departament de Sistemes Informàtics i Computació, Universitat Politècnica de València. Departamento de Estadística e Investigación Operativa Aplicadas y Calidad - Departament d'Estadística i Investigació Operativa Aplicades i Qualitat, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Nvidia, Generalitat Valenciana, Gisbert Soler, Víctor, Jiménez-Serrano, Santiago, Roses-Albert, Eduardo, and RODRIGO BORT, MIGUEL
Abstract: [EN] Background: The Electrocardiographic Imaging (ECGI) technique, used to non-invasively reconstruct the epicardial electrical activity, requires an accurate model of the atria and torso anatomy. Here we evaluate a new automatic methodology able to locate the atrial anatomy within the torso based on an intrinsic electrical parameter of the ECGI solution. Methods: In 28 realistic simulations of the atrial electrical activity, we randomly displaced the atrial anatomy for +/- 2.5 cm and +/- 30 degrees on each axis. An automatic optimization method based on the L-curve curvature was used to estimate the original position using exclusively non-invasive data. Results: The automatic optimization algorithm located the atrial anatomy with a deviation of 0.5 +/- 0.5 cm in position and 16.0 +/- 10.7 degrees in orientation. With these approximate locations, the obtained electrophysiological maps reduced the average error in atrial rate measures from 1.1 +/- 1.1 Hz to 0.5 +/- 1.0 Hz and in the phase singularity position from 7.2 +/- 4.0 cm to 1.6 +/- 1.7 cm (p < 0.01). Conclusions: This proposed automatic optimization may help to solve spatial inaccuracies provoked by cardiac motion or respiration, as well as to use ECGI on torso and atrial anatomies from different medical image systems.
Published: 2020

30. The first wave of the Spanish COVID-19 epidemic was associated with early introductions and fast spread of a dominating genetic variant

Author: Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), European Commission, European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), López, Mariana G. [0000-0002-2216-9232], Chiner-Oms, Álvaro [0000-0002-0463-0101], Coscolla, Mireia [0000-0003-0752-0538], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], López, Mariana G., Chiner-Oms, Álvaro, García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D’Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Alberola, Juan, Albert, Eliseo, Aranzamendi Zaldumbide, Maitane, Bea-Escudero, María Pilar, Boga, José Antonio, Bordoy, Antoni E., Canut, Andrés, Carvajal, Ana, Cilla Eguiluz, Gustavo, Cordón Rodríguez, María Luz, Costa-Alcalde, José J., Toro, María de, Toro Peinado, Inmaculada de, Pozo, José Luis del, Duchêne, Sebastián, Fernández-Pinero, Jovita, Fuster Escrivá, Begoña, Gimeno, Concepción, González Galán, Verónica, Gonzalo Jimeno, Nieves, Hernáez Crespo, Silvia, Herranz, Marta, Lepe, José A., López-Hontangas, José Luis, Marcos, María Ángeles, Martín, Vicente, Martró, Elisa, Milagro Beamonte, Ana, Montes Ros, Milagrosa, Moreno-Muñoz, Rosario, Navarro, David, Navarro-Marí, José María, Not, Anna, Oliver, Antonio, Palop-Borrás, Begoña, Parra Grande, Mónica, Pedrosa-Corral, Irene, Pérez González, María Carmen, Pérez-Lago, Laura, Piñeiro Vázquez, Luis, Rabella, Nuria, Reina, Jordi, Rezusta, Antonio, Robles Fonseca, Lorena, Rodríguez-Villodres, Ángel, Sanbonmatsu-Gámez, Sara, Sicilia, Jon, Tirado Balaguer, María Dolores, Torres, Ignacio, Tristancho, Alexander, Marimón, José María, Coscollá, Mireia, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), European Commission, European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), López, Mariana G. [0000-0002-2216-9232], Chiner-Oms, Álvaro [0000-0002-0463-0101], Coscolla, Mireia [0000-0003-0752-0538], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], López, Mariana G., Chiner-Oms, Álvaro, García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D’Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Alberola, Juan, Albert, Eliseo, Aranzamendi Zaldumbide, Maitane, Bea-Escudero, María Pilar, Boga, José Antonio, Bordoy, Antoni E., Canut, Andrés, Carvajal, Ana, Cilla Eguiluz, Gustavo, Cordón Rodríguez, María Luz, Costa-Alcalde, José J., Toro, María de, Toro Peinado, Inmaculada de, Pozo, José Luis del, Duchêne, Sebastián, Fernández-Pinero, Jovita, Fuster Escrivá, Begoña, Gimeno, Concepción, González Galán, Verónica, Gonzalo Jimeno, Nieves, Hernáez Crespo, Silvia, Herranz, Marta, Lepe, José A., López-Hontangas, José Luis, Marcos, María Ángeles, Martín, Vicente, Martró, Elisa, Milagro Beamonte, Ana, Montes Ros, Milagrosa, Moreno-Muñoz, Rosario, Navarro, David, Navarro-Marí, José María, Not, Anna, Oliver, Antonio, Palop-Borrás, Begoña, Parra Grande, Mónica, Pedrosa-Corral, Irene, Pérez González, María Carmen, Pérez-Lago, Laura, Piñeiro Vázquez, Luis, Rabella, Nuria, Reina, Jordi, Rezusta, Antonio, Robles Fonseca, Lorena, Rodríguez-Villodres, Ángel, Sanbonmatsu-Gámez, Sara, Sicilia, Jon, Tirado Balaguer, María Dolores, Torres, Ignacio, Tristancho, Alexander, Marimón, José María, Coscollá, Mireia, González-Candelas, Fernando, and Comas, Iñaki
Abstract: The COVID-19 pandemic has shaken the world since the beginning of 2020. Spain is among the European countries with the highest incidence of the disease during the first pandemic wave. We established a multidisciplinar consortium to monitor and study the evolution of the epidemic, with the aim of contributing to decision making and stopping rapid spreading across the country. We present the results for 2170 sequences from the first wave of the SARS-Cov-2 epidemic in Spain and representing 12% of diagnosed cases until 14th March. This effort allows us to document at least 500 initial introductions, between early February-March from multiple international sources. Importantly, we document the early raise of two dominant genetic variants in Spain (Spanish Epidemic Clades), named SEC7 and SEC8, likely amplified by superspreading events. In sharp contrast to other non-Asian countries those two variants were closely related to the initial variants of SARS-CoV-2 described in Asia and represented 40% of the genome sequences analyzed. The two dominant SECs were widely spread across the country compared to other genetic variants with SEC8 reaching a 60% prevalence just before the lockdown. Employing Bayesian phylodynamic analysis, we inferred a reduction in the effective reproductive number of these two SECs from around 2.5 to below 0.5 after the implementation of strict public-health interventions in mid March. The effects of lockdown on the genetic variants of the virus are reflected in the general replacement of preexisting SECs by a new variant at the beginning of the summer season. Our results reveal a significant difference in the genetic makeup of the epidemic in Spain and support the effectiveness of lockdown measures in controlling virus spread even for the most successful genetic variants. Finally, earlier control of SEC7 and particularly SEC8 might have reduced the incidence and impact of COVID-19 in our country.
Published: 2020

31. The first wave of the Spanish COVID-19 epidemic was associated with early introductions and fast spread of a dominating genetic variant

Author: López, Mariana G., primary, Chiner-Oms, Álvaro, additional, de Viedma, Darío García, additional, Ruiz-Rodriguez, Paula, additional, Bracho, Maria Alma, additional, Cancino-Muñoz, Irving, additional, D’Auria, Giuseppe, additional, de Marco, Griselda, additional, García-González, Neris, additional, Goig, Galo Adrian, additional, Gómez-Navarro, Inmaculada, additional, Jiménez-Serrano, Santiago, additional, Martinez-Priego, Llúcia, additional, Ruiz-Hueso, Paula, additional, Ruiz-Roldán, Lidia, additional, Torres-Puente, Manuela, additional, Alberola, Juan, additional, Albert, Eliseo, additional, Zaldumbide, Maitane Aranzamendi, additional, Bea-Escudero, María Pilar, additional, Boga, Jose Antonio, additional, Bordoy, Antoni E., additional, Canut-Blasco, Andrés, additional, Carvajal, Ana, additional, Eguiluz, Gustavo Cilla, additional, Rodríguez, Maria Luz Cordón, additional, Costa-Alcalde, José J., additional, de Toro, María, additional, de Toro Peinado, Inmaculada, additional, del Pozo, Jose Luis, additional, Duchêne, Sebastián, additional, Fernández-Pinero, Jovita, additional, Escrivá, Begoña Fuster, additional, Cardona, Concepción Gimeno, additional, Galán, Verónica González, additional, Jiménez, Nieves Gonzalo, additional, Crespo, Silvia Hernáez, additional, Herranz, Marta, additional, Lepe, José Antonio, additional, López-Hontangas, José Luis, additional, Marcos, Maria Ángeles, additional, Martín, Vicente, additional, Martró, Elisa, additional, Beamonte, Ana Milagro, additional, Ros, Milagrosa Montes, additional, Moreno-Muñoz, Rosario, additional, Navarro, David, additional, Navarro-Marí, José María, additional, Not, Anna, additional, Oliver, Antonio, additional, Palop-Borrás, Begoña, additional, Grande, Mónica Parra, additional, Pedrosa-Corral, Irene, additional, Gonzalez, Maria Carmen Perez, additional, Pérez-Lago, Laura, additional, Vázquez, Luis Piñeiro, additional, Rabella, Nuria, additional, Reina, Jordi, additional, Rezusta, Antonio, additional, Fonseca, Lorena Robles, additional, Rodríguez-Villodres, Ángel, additional, Sanbonmatsu-Gámez, Sara, additional, Sicilia, Jon, additional, Balaguer, María Dolores Tirado, additional, Torres, Ignacio, additional, Tristancho, Alexander, additional, Marimón, José María, additional, Coscolla, Mireia, additional, González-Candelas, Fernando, additional, and Comas, Iñaki, additional
Published: 2020
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32. Clasificación automática de registros ECG para la detección de Fibrilación Auricular y otros ritmos cardiacos

Author: Jiménez Serrano, Santiago
Subjects: Support Vector Machine, Neural Networks, Reconeixement de Formes i Imatge Digital [Máster Universitario en Inteligencia Artificial, Reconocimiento de Formas e Imagen Digital-Màster Universitari en Intel·Ligència Artificial], ECG, feature extraction, extracción de características, clasificación, Naïve Bayes, TECNOLOGIA ELECTRONICA, feature selection, classification, selección de características, intervalo RR, Máster Universitario en Inteligencia Artificial, Reconocimiento de Formas e Imagen Digital-Màster Universitari en Intel·Ligència Artificial: Reconeixement de Formes i Imatge Digital, Atrial Fibrillation, RR interval, Redes Neuronales, Fibrilación Auricular, LENGUAJES Y SISTEMAS INFORMATICOS
Abstract: La importancia clínica de las arritmias cardiacas está aumentando, junto con su incidencia y prevalencia, principalmente asociadas con el envejecimiento de la población. Entre estas enfermedades destaca la Fibrilación Auricular (FA) ya que es el tipo de arritmia sostenida más común en adultos con una tendencia creciente más significativa, siendo en muchas ocasiones difícil de diagnosticar debido a un comportamiento paroxístico y/o la ausencia de síntomas en algunos casos. Por otro lado, hoy en día estamos en un escenario en el que los dispositivos portátiles o ¿wearables¿ están ganando gran interés como dispositivos de monitorización, tanto en investigación como en ámbitos clínicos. Sin embargo, los métodos automáticos para proporcionar un diagnóstico fiable de la FA utilizando las señales de electrocardiograma (ECG) proporcionadas por dispositivos portátiles son todavía un reto, especialmente si también se consideran otros ritmos normales o patológicos. El objetivo de este Trabajo Final de Máster es proporcionar diversos modelos de clasificación junto con su rendimiento para discriminar registros cortos de ECG de una única derivación entre cuatro grupos: ritmo normal (N), FA (A), otros ritmos (O) y ruidoso (~). Como base de datos para este estudio se utilizaron 8.528 registros de ECG de una única derivación con duraciones entre 9 y 60 segundos, proporcionados en el contexto de la competición 2017 PhysioNet/Computing in Cardiology Challenge. La estrategia propuesta en este trabajo se basa inicialmente en la extracción automática de características derivadas de la actividad ventricular de las señales ECG. Posteriormente se realizó una selección de características utilizando dos metodologías distintas: Backward Elimination y Forward Selection. Finalmente, las características seleccionadas se utilizaron para entrenar y evaluar mediante validación cruzada el rendimiento de diferentes modelos de clasificación, principalmente redes neuronales de tipo feedforward (FFNN), así como modelos Naïve Bayes y Support Vector Machine (SVM). A cada uno de estos modelos se le realizó un ajuste de parámetros de entrenamiento mediante grid-search durante la fase de validación. Los resultados mostraron que los modelos que presentaban mejor rendimiento de clasificación fueron las redes neuronales (F1=0.75), seguidas de cerca por los modelos SVM (F1=0.73), mientras que Naïve Bayes presentó el menor rendimiento (F1=0.67). Asimismo, también se demostró que la mayor dificultad de este problema se encuentra en la identificación de otros ritmos anómalos distintos a la fibrilación auricular, así como de los registros ruidosos. Dado que las señales utilizadas comparten muchas características con las adquiridas con dispositivos móviles, los modelos de clasificación resultantes podrían ser buenos candidatos para ser implementados en sistemas de gestión de pacientes con dispositivos wearables, ya que este enfoque tiene un bajo consumo computacional durante la clasificación., The clinical importance of cardiac arrhythmias is increasing, along with its incidence and prevalence, mainly associated with the aging of the population. Among these diseases Atrial Fibrillation (AF) stands out since it is the type of sustained arrhythmia most common in adults with a more significant growing tendency, being in many cases difficult to diagnose due to a paroxysmal behavior and/or the absence of symptoms in some patients. On the other hand, today we are in a scenario in which mobile devices or ¿wearables¿ are gaining great interest as monitoring devices, both in research and in clinical settings. However, automatic methods to provide a reliable diagnosis of AF using electrocardiogram signals (ECG) provided by mobile devices are still a challenge, especially if other normal or pathological rhythms are also considered. The main objective of this Final Master's Thesis is to provide different classification models together with their performance to discriminate short ECG single-lead records among four different groups: normal rhythm (N), FA (A), other rhythms (O) and noisy (~). As database for this study, 8,528 single-lead ECG records lasting among 9 and 60 seconds were used, provided in the context of the 2017 PhysioNet/Computing in Cardiology Challenge. The proposed strategy in this work is initially based on the automatic extraction of features mainly derived from the ventricular activity of the ECG signals. Next, a selection of characteristics was made using two different methodologies: Backward Elimination and Forward Selection. Finally, the selected features were used to train and evaluate through cross-validation the performance of different classification models, mainly feedforward neural networks (FFNN), as well as Naïve Bayes and Support Vector Machine (SVM) models. The training parameters for each of these models were tuned though a grid-search validation process. Results showed that the models with the best classification performance were the neural networks (F_1=0.75), followed closely by the SVM models (F_1=0.73), while Naïve Bayes presented the lowest performance (F_1=0.67). Likewise, it was also proved that the greatest difficulty of this problem lies on the identification of other anomalous rhythms other than atrial fibrillation, as well as in the noisy registers. Since the signals used share many characteristics with those acquired with mobile devices, the resulting classification models could be good candidates to be implemented in patient management systems with wearable devices, since this approach has a low computational consumption during classification.
Published: 2018

33. Clasificación automática de registros ECG para la detección de Fibrilación Auricular y otros ritmos cardiacos

Author: Castells Ramón, Francisco Sales, Martínez Hinarejos, Carlos David, Universitat Politècnica de València. Departamento de Sistemas Informáticos y Computación - Departament de Sistemes Informàtics i Computació, Jiménez Serrano, Santiago, Castells Ramón, Francisco Sales, Martínez Hinarejos, Carlos David, Universitat Politècnica de València. Departamento de Sistemas Informáticos y Computación - Departament de Sistemes Informàtics i Computació, and Jiménez Serrano, Santiago
Abstract: La importancia clínica de las arritmias cardiacas está aumentando, junto con su incidencia y prevalencia, principalmente asociadas con el envejecimiento de la población. Entre estas enfermedades destaca la Fibrilación Auricular (FA) ya que es el tipo de arritmia sostenida más común en adultos con una tendencia creciente más significativa, siendo en muchas ocasiones difícil de diagnosticar debido a un comportamiento paroxístico y/o la ausencia de síntomas en algunos casos. Por otro lado, hoy en día estamos en un escenario en el que los dispositivos portátiles o ¿wearables¿ están ganando gran interés como dispositivos de monitorización, tanto en investigación como en ámbitos clínicos. Sin embargo, los métodos automáticos para proporcionar un diagnóstico fiable de la FA utilizando las señales de electrocardiograma (ECG) proporcionadas por dispositivos portátiles son todavía un reto, especialmente si también se consideran otros ritmos normales o patológicos. El objetivo de este Trabajo Final de Máster es proporcionar diversos modelos de clasificación junto con su rendimiento para discriminar registros cortos de ECG de una única derivación entre cuatro grupos: ritmo normal (N), FA (A), otros ritmos (O) y ruidoso (~). Como base de datos para este estudio se utilizaron 8.528 registros de ECG de una única derivación con duraciones entre 9 y 60 segundos, proporcionados en el contexto de la competición 2017 PhysioNet/Computing in Cardiology Challenge. La estrategia propuesta en este trabajo se basa inicialmente en la extracción automática de características derivadas de la actividad ventricular de las señales ECG. Posteriormente se realizó una selección de características utilizando dos metodologías distintas: Backward Elimination y Forward Selection. Finalmente, las características seleccionadas se utilizaron para entrenar y evaluar mediante validación cruzada el rendimiento de diferentes modelos de clasificación, principalmente redes neuronales de tipo feedforward (FFNN), a, The clinical importance of cardiac arrhythmias is increasing, along with its incidence and prevalence, mainly associated with the aging of the population. Among these diseases Atrial Fibrillation (AF) stands out since it is the type of sustained arrhythmia most common in adults with a more significant growing tendency, being in many cases difficult to diagnose due to a paroxysmal behavior and/or the absence of symptoms in some patients. On the other hand, today we are in a scenario in which mobile devices or ¿wearables¿ are gaining great interest as monitoring devices, both in research and in clinical settings. However, automatic methods to provide a reliable diagnosis of AF using electrocardiogram signals (ECG) provided by mobile devices are still a challenge, especially if other normal or pathological rhythms are also considered. The main objective of this Final Master's Thesis is to provide different classification models together with their performance to discriminate short ECG single-lead records among four different groups: normal rhythm (N), FA (A), other rhythms (O) and noisy (~). As database for this study, 8,528 single-lead ECG records lasting among 9 and 60 seconds were used, provided in the context of the 2017 PhysioNet/Computing in Cardiology Challenge. The proposed strategy in this work is initially based on the automatic extraction of features mainly derived from the ventricular activity of the ECG signals. Next, a selection of characteristics was made using two different methodologies: Backward Elimination and Forward Selection. Finally, the selected features were used to train and evaluate through cross-validation the performance of different classification models, mainly feedforward neural networks (FFNN), as well as Naïve Bayes and Support Vector Machine (SVM) models. The training parameters for each of these models were tuned though a grid-search validation process. Results showed that the models with the best classification performance were the
Published: 2018

34. Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status

Author: Universitat Politècnica de València. Instituto Universitario de Aplicaciones de las Tecnologías de la Información - Institut Universitari d'Aplicacions de les Tecnologies de la Informació, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Ministerio de Economía y Competitividad, Filgueiras-Rama, David, Calvo Saiz, Conrado Javier, Salvador-Montañés, Óscar, Cádenas, Rosalia, Ruiz-Cantador, Jose, Armada, Eduardo, Rey, Juan Ramón, Merino, J.L., Peinado, Rafael, Pérez-Castellano, Nicasio, Pérez-Villacastín, Julián, Quintanilla, Jorge G., Jiménez Serrano, Santiago, Castells, Francisco, Millet Roig, José, Universitat Politècnica de València. Instituto Universitario de Aplicaciones de las Tecnologías de la Información - Institut Universitari d'Aplicacions de les Tecnologies de la Informació, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Ministerio de Economía y Competitividad, Filgueiras-Rama, David, Calvo Saiz, Conrado Javier, Salvador-Montañés, Óscar, Cádenas, Rosalia, Ruiz-Cantador, Jose, Armada, Eduardo, Rey, Juan Ramón, Merino, J.L., Peinado, Rafael, Pérez-Castellano, Nicasio, Pérez-Villacastín, Julián, Quintanilla, Jorge G., Jiménez Serrano, Santiago, Castells, Francisco, and Millet Roig, José
Abstract: Background: Early prognosis in comatose survivors after cardiac arrest due to ventricular fibrillation (VF) is unreliable, especially in patients undergoing mild hypothermia. We aimed at developing a reliable risk-score to enable early prediction of cerebral performance and survival. Methods: Sixty-one out of 239 consecutive patients undergoing mild hypothermia after cardiac arrest, with eventual return of spontaneous circulation (ROSC), and comatose status on admission fulfilled the inclusion criteria. Background clinical variables, VF time and frequency domain fundamental variables were considered. The primary and secondary outcomes were a favorable neurological performance (FNP) during hospitalization and survival to hospital discharge, respectively. The predictive model was developed in a retrospective cohort (n = 32; September 2006 September 2011, 48.5 ± 10.5 months of follow-up) and further validated in a prospective cohort (n = 29; October 2011 July 2013, 5 ± 1.8 months of follow-up). Results: FNP was present in 16 (50.0%) and 21 patients (72.4%) in the retrospective and prospective cohorts, respectively. Seventeen (53.1%) and 21 patients (72.4%), respectively, survived to hospital discharge. Both outcomes were significantly associated (p < 0.001). Retrospective multivariate analysis provided a prediction model (sensitivity = 0.94, specificity = 1) that included spectral dominant frequency, derived power density and peak ratios between high and low frequency bands, and the number of shocks delivered before ROSC. Validation on the prospective cohort showed sensitivity = 0.88 and specificity = 0.91. A model-derived risk-score properly predicted 93% of FNP. Testing the model on follow-up showed a c-statistic ≥ 0.89. Conclusions: A spectral analysis-based model reliably correlates time-dependent VF spectral changes with acute cerebral injury in comatose survivors undergoing mild hypothermia after cardiac arrest.
Published: 2015

35. Desarrollo de modelos predictivos y una aplicación móvil para la predicción de la depresión postparto

Author: Jiménez Serrano, Santiago
Subjects: redes neuronales, Classifiers, Neural Networks, Embarazo, Depresión postparto, Decision suport, Ayuda a la decisión, Máster Universitario en Ingeniería Biomédica-Màster Universitari en Enginyeria Biomèdica, Pregnancy, Android, Postpartum depression, FISICA APLICADA, Clasificadores
Abstract: [EN] Postpartum depression is a disabling universal disease that affects many women from different countries during a key life stage for her and her newborn. The aim of this research involved the creation of classification models for postpartum depression based on clinical and patient questionnaires. We analyzed these data and applied a methodology of experimentation, validation and evaluation of different classification models. The classifiers with the best balance between sensitivity and specificity were integrated into a clinical decision support system for Android mobile platforms. It is intended, therefore, to put in clinicians and patients hands, a tool that aims to prevent the disease as well as to detect the risk population. That¿s why the final application comes in two versions, one for medical experts, and another one simpler for women who have just given birth., [ES] La depresión postparto es una enfermedad universal incapacitante que afecta a muchas mujeres de diferentes países durante una etapa vital clave para ella y su recién nacido. El objetivo del presente trabajo ha consistido en la creación de modelos de clasificación de la depresión postparto basados en datos clínicos y cuestionarios a pacientes. Se analizaron dichos datos y se aplicó una metodología de experimentación para el desarrollo, validación y evaluación de diferentes modelos de clasificación. Los clasificadores que presentaron un mejor balance entre sensibilidad y especificidad se integraron en un sistema de ayuda a la decisión clínica para plataformas móviles Android. Se ha pretendido pues, poner en manos tanto de personal clínico como de pacientes una herramienta que ayude en la prevención de la enfermedad y en la detección de población de riesgo. Es por eso que la aplicación final se presenta en dos versiones, una para expertos médicos, y otra más sencilla para las mujeres que acaban de dar a luz.
Published: 2013

36. Optimización de rutas de vuelo para un hidroavión en sus tareas de vigilancia de incendios forestales

Author: Jiménez Serrano, Santiago
Subjects: Travelling salesman problem, Planes de vuelo, Ingeniería Informática-Enginyeria Informàtica, Problema del viajante de comercio, Xml, Tsp, Ramificación y poda, C#, Effis, net, Flightplan, Branch and bound, Web feature service, Algoritmos genéticos, Wfs
Abstract: En este trabajo se ha desarrollado un conjunto de bibliotecas de clases (API), junto con las interfaces gráficas de usuario que las utilizan, para generar la ruta de vuelo óptima que ha de seguir un hidroavión en sus tareas de vigilancia y extinción de incendios. Para ello se tiene en cuenta la información extraída del sitio web del EFFIS (European Forest Fire Information System), donde se ofrece en tiempo real los hotspots (posibles incendios detectados por el instrumento MODIS a bordo de satélites) recientes y antiguos, y los fuegos confirmados por este mismo organismo (fires). Una vez extraída esta información, donde se incluye la geolocalización de estos puntos (latitud, longitud), a los que llamaremos waypoints, se ha implementado algunas variantes que solucionan el problema del TSP (Travelling Salesman Problem). A través de algoritmos que hacen uso de las técnicas de `Ramificación y Poda¿ y `Algoritmos Genéticos¿, creamos una ruta óptima en algunos casos, subóptima en otros. Finalmente, esta ruta se convierte en un archivo XML que sigue las especificaciones de un plan de vuelo descritas en el `Flight Plan Specification Language¿, utilizado dentro de la plataforma ISIS para visualizar, simular e incluso hacer volar aparatos reales en modo piloto automático. Una vez obtenido este archivo, lo podremos visualizar directamente en el mapa a través del Flight Plan Monitor que provee la plataforma ISIS. La aplicación se ha desarrollado en el IDE Visual Studio 2010 bajo el sistema operativo Windows 7 y el .Net Framework 4.0. El lenguaje de programación utilizado ha sido C#
Published: 2011

37. A Mobile Health Application to Predict Postpartum Depression Based on Machine Learning

Author: Jiménez-Serrano, Santiago, primary, Tortajada, Salvador, additional, and García-Gómez, Juan Miguel, additional
Published: 2015
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38. Desarrollo de modelos predictivos y una aplicación móvil para la predicción de la depresión postparto

Author: García Gómez, Juan Miguel, Tortajada Velert, Salvador, Universitat Politècnica de València. Servicio de Alumnado - Servei d'Alumnat, Jiménez Serrano, Santiago, García Gómez, Juan Miguel, Tortajada Velert, Salvador, Universitat Politècnica de València. Servicio de Alumnado - Servei d'Alumnat, and Jiménez Serrano, Santiago
Abstract: [EN] Postpartum depression is a disabling universal disease that affects many women from different countries during a key life stage for her and her newborn. The aim of this research involved the creation of classification models for postpartum depression based on clinical and patient questionnaires. We analyzed these data and applied a methodology of experimentation, validation and evaluation of different classification models. The classifiers with the best balance between sensitivity and specificity were integrated into a clinical decision support system for Android mobile platforms. It is intended, therefore, to put in clinicians and patients hands, a tool that aims to prevent the disease as well as to detect the risk population. That¿s why the final application comes in two versions, one for medical experts, and another one simpler for women who have just given birth., [ES] La depresión postparto es una enfermedad universal incapacitante que afecta a muchas mujeres de diferentes países durante una etapa vital clave para ella y su recién nacido. El objetivo del presente trabajo ha consistido en la creación de modelos de clasificación de la depresión postparto basados en datos clínicos y cuestionarios a pacientes. Se analizaron dichos datos y se aplicó una metodología de experimentación para el desarrollo, validación y evaluación de diferentes modelos de clasificación. Los clasificadores que presentaron un mejor balance entre sensibilidad y especificidad se integraron en un sistema de ayuda a la decisión clínica para plataformas móviles Android. Se ha pretendido pues, poner en manos tanto de personal clínico como de pacientes una herramienta que ayude en la prevención de la enfermedad y en la detección de población de riesgo. Es por eso que la aplicación final se presenta en dos versiones, una para expertos médicos, y otra más sencilla para las mujeres que acaban de dar a luz.
Published: 2014

39. Exploiting multiple ASR outputs for a spoken language understanding task

Author: Universitat Politècnica de València. Departamento de Sistemas Informáticos y Computación - Departament de Sistemes Informàtics i Computació, Universitat Politècnica de València. Instituto Universitario de Aplicaciones de las Tecnologías de la Información - Institut Universitari d'Aplicacions de les Tecnologies de la Informació, Ministerio de Ciencia e Innovación, Ministerio de Educación, Cultura y Deporte, Calvo Lance, Marcos, García Granada, Fernando, Hurtado Oliver, Lluis Felip, Jiménez Serrano, Santiago, Sanchís Arnal, Emilio, Universitat Politècnica de València. Departamento de Sistemas Informáticos y Computación - Departament de Sistemes Informàtics i Computació, Universitat Politècnica de València. Instituto Universitario de Aplicaciones de las Tecnologías de la Información - Institut Universitari d'Aplicacions de les Tecnologies de la Informació, Ministerio de Ciencia e Innovación, Ministerio de Educación, Cultura y Deporte, Calvo Lance, Marcos, García Granada, Fernando, Hurtado Oliver, Lluis Felip, Jiménez Serrano, Santiago, and Sanchís Arnal, Emilio
Abstract: The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-01931-4_19, In this paper, we present an approach to Spoken Language Understanding, where the input to the semantic decoding process is a composition of multiple hypotheses provided by the Automatic Speech Recognition module. This way, the semantic constraints can be applied not only to a unique hypothesis, but also to other hypotheses that could represent a better recognition of the utterance. To do this, we have developed an algorithm to combine multiple sentences into a weighted graph of words, which is the input to the semantic decoding process. It has also been necessary to develop a specific algorithm to process these graphs of words according to the statistical models that represent the semantics of the task. This approach has been evaluated in a SLU task in Spanish. Results, considering different configurations of ASR outputs, show the better behavior of the system when a combination of hypotheses is considered.
Published: 2013

40. hITeQ: A new workflow-based computing environment for streamlining discovery. Application in materials science

Author: Universitat Politècnica de València. Instituto Universitario Mixto de Tecnología Química - Institut Universitari Mixt de Tecnologia Química, Universitat Politècnica de València. Instituto Universitario de Aplicaciones de las Tecnologías de la Información - Institut Universitari d'Aplicacions de les Tecnologies de la Informació, Universitat Politècnica de València. Departamento de Química - Departament de Química, European Commission, Baumes, Laurent Allan, Jiménez Serrano, Santiago, Corma Canós, Avelino, Universitat Politècnica de València. Instituto Universitario Mixto de Tecnología Química - Institut Universitari Mixt de Tecnologia Química, Universitat Politècnica de València. Instituto Universitario de Aplicaciones de las Tecnologías de la Información - Institut Universitari d'Aplicacions de les Tecnologies de la Informació, Universitat Politècnica de València. Departamento de Química - Departament de Química, European Commission, Baumes, Laurent Allan, Jiménez Serrano, Santiago, and Corma Canós, Avelino
Abstract: [EN] This paper presents the implementation of the recent methodology called Adaptable Time Warping (ATW) for the automatic identification of mixture of crystallographic phases from powder X-ray diffraction data, inside the framework of a new integrative platform named hITeQ. The methodology is encapsulated into a so-called workflow, and we explore the benefits of such an environment for streamlining discovery in R&D. Beside the fact that ATW successfully identifies and classifies crystalline phases from powder XRD for the very complicated case of zeolite ITQ-33 for which has been employed a high throughput synthesis process, we stress on the numerous difficulties encountered by academic laboratories and companies when facing the integration of new software or techniques. It is shown how an integrative approach provides a real asset in terms of cost, efficiency, and speed due to a unique environment that supports well-defined and reusable processes, improves knowledge management, and handles properly multi-disciplinary teamwork, and disparate data structures and protocols.
Published: 2011

41. Optimización de rutas de vuelo para un hidroavión en sus tareas de vigilancia de incendios forestales

Author: Ruiz García, Juan Carlos, Universitat Politècnica de València. Escola Tècnica Superior d'Enginyeria Informàtica, Jiménez Serrano, Santiago, Ruiz García, Juan Carlos, Universitat Politècnica de València. Escola Tècnica Superior d'Enginyeria Informàtica, and Jiménez Serrano, Santiago
Abstract: En este trabajo se ha desarrollado un conjunto de bibliotecas de clases (API), junto con las interfaces gráficas de usuario que las utilizan, para generar la ruta de vuelo óptima que ha de seguir un hidroavión en sus tareas de vigilancia y extinción de incendios. Para ello se tiene en cuenta la información extraída del sitio web del EFFIS (European Forest Fire Information System), donde se ofrece en tiempo real los hotspots (posibles incendios detectados por el instrumento MODIS a bordo de satélites) recientes y antiguos, y los fuegos confirmados por este mismo organismo (fires). Una vez extraída esta información, donde se incluye la geolocalización de estos puntos (latitud, longitud), a los que llamaremos waypoints, se ha implementado algunas variantes que solucionan el problema del TSP (Travelling Salesman Problem). A través de algoritmos que hacen uso de las técnicas de `Ramificación y Poda¿ y `Algoritmos Genéticos¿, creamos una ruta óptima en algunos casos, subóptima en otros. Finalmente, esta ruta se convierte en un archivo XML que sigue las especificaciones de un plan de vuelo descritas en el `Flight Plan Specification Language¿, utilizado dentro de la plataforma ISIS para visualizar, simular e incluso hacer volar aparatos reales en modo piloto automático. Una vez obtenido este archivo, lo podremos visualizar directamente en el mapa a través del Flight Plan Monitor que provee la plataforma ISIS. La aplicación se ha desarrollado en el IDE Visual Studio 2010 bajo el sistema operativo Windows 7 y el .Net Framework 4.0. El lenguaje de programación utilizado ha sido C#
Published: 2011

42. Boosting theorical zeolitic framework generation for the determination of new materials structures using GPU programming

Author: Universitat Politècnica de València. Instituto Universitario Mixto de Tecnología Química - Institut Universitari Mixt de Tecnologia Química, Universitat Politècnica de València. Servicio de Alumnado - Servei d'Alumnat, Universitat Politècnica de València. Departamento de Química - Departament de Química, Baumes, Laurent Allan, Kruger, Frederic, Jiménez Serrano, Santiago, Collet, Pierre, Corma Canós, Avelino, Universitat Politècnica de València. Instituto Universitario Mixto de Tecnología Química - Institut Universitari Mixt de Tecnologia Química, Universitat Politècnica de València. Servicio de Alumnado - Servei d'Alumnat, Universitat Politècnica de València. Departamento de Química - Departament de Química, Baumes, Laurent Allan, Kruger, Frederic, Jiménez Serrano, Santiago, Collet, Pierre, and Corma Canós, Avelino
Abstract: [EN] Evolutionary algorithms have proved to be efficient for solving complicated optimization problems. On the other hand, the many-core architecture in graphical cards "General Purpose Graphic Processing Unit" (GPGPU) offers one of the most attractive cost/performance ratio. Using such hardware, the manuscript shows how an efficiently implemented genetic algorithm with a simple fitness function allows boosting the determination of zeolite structures. A case study is presented. © 2011 the Societies Owner.
Published: 2011

43. Desarrollo de nuevos marcadores y clasificadores de bajo coste computacional para identificar afecciones cardiacas en registros ECG

Author: Jiménez Serrano, Santiago, primary
Full Text: View/download PDF

44. Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

Author: Medicina Preventiva, Hodcroft, Emma B., Zuber, Moira, Nadeau, Sarah, Vaughan, Timothy G., Crawford, Katharine H. D., Althaus, Christian L., Reichmuth, Martina L., Bowen, John E., Walls, Alexandra C., Corti, Davide, Bloom, Jesse D., Veesler, David, Mateo, David, Hernando, Alberto, Comas, Iñaki, González-Candelas, Fernando, Goig, Galo Adrian, Chiner-Oms, Álvaro, Cancino-Muñoz, Irving, López, Mariana Gabriela, Torres-Puente, Manuela, Gomez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Ruiz-Roldán, Lidia, Bracho, María Alma, García-González, Neris, Martínez-Priego, Llúcia, Galán-Vendrell, Inmaculada, Ruiz-Hueso, Paula, De Marco, Griselda, Ferrús, Maria Loreto, Carbó-Ramírez, Sandra, D’Auria, Giuseppe, Coscollá, Mireia, Ruiz-Rodríguez, Paula, Roig-Sena, Francisco Javier, Sanmartín, Isabel, Garcia-Souto, Daniel, Pequeno-Valtierra, Ana, Tubio, Jose M. C., Rodríguez-Castro, Jorge, Rabella, Nuria, Navarro, Ferrán, Miró, Elisenda, Rodríguez-Iglesias, Manuel, Galán-Sanchez, Fátima, Rodriguez-Pallares, Salud, de Toro, María, Escudero, María Bea, Azcona-Gutiérrez, José Manuel, Alberdi, Miriam Blasco, Mayor, Alfredo, García-Basteiro, Alberto L., Moncunill, Gemma, Dobaño, Carlota, Cisteró, Pau, García-de-Viedma, Darío, Pérez-Lago, Laura, Herranz, Marta, Sicilia, Jon, Catalán-Alonso, Pilar, Muñoz, Patricia, Muñoz-Cuevas, Cristina, Rodríguez-Rodríguez, Guadalupe, Alberola-Enguidanos, Juan, Nogueira, Jose Miguel, Camarena, Juan José, Rezusta, Antonio, Tristancho-Baró, Alexander, Milagro, Ana, Martínez-Cameo, Nieves Felisa, Gracia-Grataloup, Yolanda, Martró, Elisa, Bordoy, Antoni E., Not, Anna, Antuori-Torres, Adrián, Benito, Rafael, Algarate, Sonia, Bueno, Jessica, del Pozo, Jose Luis, Boga, Jose Antonio, Castelló-Abietar, Cristián, Rojo-Alba, Susana, Alvarez-Argüelles, Marta Elena, Melon, Santiago, Aranzamendi-Zaldumbide, Maitane, Vergara-Gómez, Andrea, Fernández-Pinero, Jovita, Martínez, Miguel J., Vila, Jordi, Rubio, Elisa, Peiró-Mestres, Aida, Navero-Castillejos, Jessica, Posada, David, Valverde, Diana, Estévez-Gómez, Nuria, Fernandez-Silva, Iria, de Chiara, Loretta, Gallego-García, Pilar, Varela, Nair, Moreno, Rosario, Tirado, Maria Dolores, Gomez-Pinedo, Ulises, Gozalo-Margüello, Mónica, Eliecer-Cano, Maria, Méndez-Legaza, José Manuel, Rodríguez-Lozano, Jesus, Siller, María, Pablo-Marcos, Daniel, Oliver, Antonio, Reina, Jordi, López-Causapé, Carla, Canut-Blasco, Andrés, Hernáez-Crespo, Silvia, Cordón, Maria Luz A., Lecároz-Agara, María-Concepción, Gómez-González, Carmen, Aguirre-Quiñonero, Amaia, López-Mirones, José Israel, Fernández-Torres, Marina, Almela-Ferrer, Maria Rosario, Gonzalo-Jiménez, Nieves, Ruiz-García, Maria Montserrat, Galiana, Antonio, Sanchez-Almendro, Judith, Cilla, Gustavo, Montes, Milagrosa, Piñeiro, Luis, Sorarrain, Ane, Marimón, José María, Gomez-Ruiz, Maria Dolores, López-Hontangas, José Luis, González Barberá, Eva M., Navarro-Marí, José María, Pedrosa-Corral, Irene, Sanbonmatsu-Gámez, Sara, Pérez-González, Carmen, Chamizo-López, Francisco, Bordes-Benítez, Ana, Navarro, David, Albert, Eliseo, Torres, Ignacio, Gascón, Isabel, Torregrosa-Hetland, Cristina Juana, Pastor-Boix, Eva, Cascales-Ramos, Paloma, Fuster-Escrivá, Begoña, Gimeno-Cardona, Concepción, Ocete, María Dolores, Medina-Gonzalez, Rafael, González-Cantó, Julia, Martínez-Macias, Olalla, Palop-Borrás, Begoña, de Toro, Inmaculada, Mediavilla-Gradolph, Maria Concepción, Pérez-Ruiz, Mercedes, González-Recio, Óscar, Gutiérrez-Rivas, Mónica, Simarro-Córdoba, Encarnación, Lozano-Serra, Julia, Robles-Fonseca, Lorena, de Salazar, Adolfo, Viñuela-González, Laura, Chueca, Natalia, García, Federico, Gómez-Camarasa, Cristina, de la Puente, Raul, Farga-Martí, Maria Amparo, Domínguez-Márquez, Victoria, Costa-Alcalde, José Javier, Trastoy, Rocío, Barbeito-Castiñeiras, Gema, Coira, Amparo, Pérez-del-Molino, María Luisa, Aguilera, Antonio, Planas, Anna M., Soriano, Alex, Fernandez-Cádenas, Israel, Pérez-Tur, Jordi, Marcos, Maria Ángeles, Moreno-Docón, Antonio, Viedma, Esther, Mingorance, Jesús, Galán-Montemayor, Juan Carlos, Parra-Grande, Mónica, Stadler, Tanja, Neher, Richard A., Carvajal Urueña, Ana María, Martín Sánchez, Vicente, Fregeneda Grandes, Juan Miguel, Molina de la Torre, Antonio José, Argüello Rodríguez, Héctor, Fernández Villa, Tania, Medicina Preventiva, Hodcroft, Emma B., Zuber, Moira, Nadeau, Sarah, Vaughan, Timothy G., Crawford, Katharine H. D., Althaus, Christian L., Reichmuth, Martina L., Bowen, John E., Walls, Alexandra C., Corti, Davide, Bloom, Jesse D., Veesler, David, Mateo, David, Hernando, Alberto, Comas, Iñaki, González-Candelas, Fernando, Goig, Galo Adrian, Chiner-Oms, Álvaro, Cancino-Muñoz, Irving, López, Mariana Gabriela, Torres-Puente, Manuela, Gomez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Ruiz-Roldán, Lidia, Bracho, María Alma, García-González, Neris, Martínez-Priego, Llúcia, Galán-Vendrell, Inmaculada, Ruiz-Hueso, Paula, De Marco, Griselda, Ferrús, Maria Loreto, Carbó-Ramírez, Sandra, D’Auria, Giuseppe, Coscollá, Mireia, Ruiz-Rodríguez, Paula, Roig-Sena, Francisco Javier, Sanmartín, Isabel, Garcia-Souto, Daniel, Pequeno-Valtierra, Ana, Tubio, Jose M. C., Rodríguez-Castro, Jorge, Rabella, Nuria, Navarro, Ferrán, Miró, Elisenda, Rodríguez-Iglesias, Manuel, Galán-Sanchez, Fátima, Rodriguez-Pallares, Salud, de Toro, María, Escudero, María Bea, Azcona-Gutiérrez, José Manuel, Alberdi, Miriam Blasco, Mayor, Alfredo, García-Basteiro, Alberto L., Moncunill, Gemma, Dobaño, Carlota, Cisteró, Pau, García-de-Viedma, Darío, Pérez-Lago, Laura, Herranz, Marta, Sicilia, Jon, Catalán-Alonso, Pilar, Muñoz, Patricia, Muñoz-Cuevas, Cristina, Rodríguez-Rodríguez, Guadalupe, Alberola-Enguidanos, Juan, Nogueira, Jose Miguel, Camarena, Juan José, Rezusta, Antonio, Tristancho-Baró, Alexander, Milagro, Ana, Martínez-Cameo, Nieves Felisa, Gracia-Grataloup, Yolanda, Martró, Elisa, Bordoy, Antoni E., Not, Anna, Antuori-Torres, Adrián, Benito, Rafael, Algarate, Sonia, Bueno, Jessica, del Pozo, Jose Luis, Boga, Jose Antonio, Castelló-Abietar, Cristián, Rojo-Alba, Susana, Alvarez-Argüelles, Marta Elena, Melon, Santiago, Aranzamendi-Zaldumbide, Maitane, Vergara-Gómez, Andrea, Fernández-Pinero, Jovita, Martínez, Miguel J., Vila, Jordi, Rubio, Elisa, Peiró-Mestres, Aida, Navero-Castillejos, Jessica, Posada, David, Valverde, Diana, Estévez-Gómez, Nuria, Fernandez-Silva, Iria, de Chiara, Loretta, Gallego-García, Pilar, Varela, Nair, Moreno, Rosario, Tirado, Maria Dolores, Gomez-Pinedo, Ulises, Gozalo-Margüello, Mónica, Eliecer-Cano, Maria, Méndez-Legaza, José Manuel, Rodríguez-Lozano, Jesus, Siller, María, Pablo-Marcos, Daniel, Oliver, Antonio, Reina, Jordi, López-Causapé, Carla, Canut-Blasco, Andrés, Hernáez-Crespo, Silvia, Cordón, Maria Luz A., Lecároz-Agara, María-Concepción, Gómez-González, Carmen, Aguirre-Quiñonero, Amaia, López-Mirones, José Israel, Fernández-Torres, Marina, Almela-Ferrer, Maria Rosario, Gonzalo-Jiménez, Nieves, Ruiz-García, Maria Montserrat, Galiana, Antonio, Sanchez-Almendro, Judith, Cilla, Gustavo, Montes, Milagrosa, Piñeiro, Luis, Sorarrain, Ane, Marimón, José María, Gomez-Ruiz, Maria Dolores, López-Hontangas, José Luis, González Barberá, Eva M., Navarro-Marí, José María, Pedrosa-Corral, Irene, Sanbonmatsu-Gámez, Sara, Pérez-González, Carmen, Chamizo-López, Francisco, Bordes-Benítez, Ana, Navarro, David, Albert, Eliseo, Torres, Ignacio, Gascón, Isabel, Torregrosa-Hetland, Cristina Juana, Pastor-Boix, Eva, Cascales-Ramos, Paloma, Fuster-Escrivá, Begoña, Gimeno-Cardona, Concepción, Ocete, María Dolores, Medina-Gonzalez, Rafael, González-Cantó, Julia, Martínez-Macias, Olalla, Palop-Borrás, Begoña, de Toro, Inmaculada, Mediavilla-Gradolph, Maria Concepción, Pérez-Ruiz, Mercedes, González-Recio, Óscar, Gutiérrez-Rivas, Mónica, Simarro-Córdoba, Encarnación, Lozano-Serra, Julia, Robles-Fonseca, Lorena, de Salazar, Adolfo, Viñuela-González, Laura, Chueca, Natalia, García, Federico, Gómez-Camarasa, Cristina, de la Puente, Raul, Farga-Martí, Maria Amparo, Domínguez-Márquez, Victoria, Costa-Alcalde, José Javier, Trastoy, Rocío, Barbeito-Castiñeiras, Gema, Coira, Amparo, Pérez-del-Molino, María Luisa, Aguilera, Antonio, Planas, Anna M., Soriano, Alex, Fernandez-Cádenas, Israel, Pérez-Tur, Jordi, Marcos, Maria Ángeles, Moreno-Docón, Antonio, Viedma, Esther, Mingorance, Jesús, Galán-Montemayor, Juan Carlos, Parra-Grande, Mónica, Stadler, Tanja, Neher, Richard A., Carvajal Urueña, Ana María, Martín Sánchez, Vicente, Fregeneda Grandes, Juan Miguel, Molina de la Torre, Antonio José, Argüello Rodríguez, Héctor, and Fernández Villa, Tania
Abstract: [EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.

45. Evolutionary and phenotypic characterization of two spike mutations in European lineage 20E of SARS-CoV-2

Author: Giuseppe D'Auria, Manuel Nuno Direito de Morais Guerreiro, Llúcia Martinez-Priego, Jorge Alfredo Pérez García, Alberto Marina, Francisco J Chamizo Lopez, Carlota Dobaño Lazaro, Miguel Julian Martinez, Elias Dahdouh, Mireia Coscolla, Ron Geller, Paula Ruiz-Rodriguez, Ricardo Ramos-ruiz, Manuela Torres-Puente, Ferran Navarro, Irene Muñoz-Gallego, Iñaki Comas, Daniel García-Souto, Clara Francés G´ómez, Santiago Jiménez-Serrano, Álvaro Chiner-Oms, Irving Cancino-Muñoz, Lidia Ruiz-Roldán, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, European Commission, Marina, Alberto [0000-0002-1334-5273], Comas, Iñaki [0000-0001-5504-9408], Chiner-Oms, Álvaro [0000-0002-0463-0101], López, Mariana G. [0000-0002-2216-9232], Jiménez Serrano, Santiago [0000-0003-2917-6053], Cancino-Muñoz, Irving [0000-0002-5261-1634], Torres-Puente, Manuela [0000-0002-8352-180X], Marina, Alberto, Comas, Iñaki, Chiner-Oms, Álvaro, López, Mariana G., Jiménez Serrano, Santiago, Cancino-Muñoz, Irving, and Torres-Puente, Manuela
Subjects: Lineage (genetic), Single-nucleotide polymorphism, Spike, Genome, Viral, Biology, Adaptive mutations, Microbiology, Neutralization, Virus, Evolution, Molecular, Neutralization Tests, Virology, Genotype, Humans, Homoplasy, HR2, Infectivity, Genetics, variants, SARS-CoV-2, Variants, COVID-19, Genetic Variation, homoplasy, spike, Antibodies, Neutralizing, Phenotype, QR1-502, Europe, Mutation, Spike Glycoprotein, Coronavirus, biology.protein, HR2, SARS-CoV-2, adaptive mutations, antibody escape, homoplasy, spike, variants, antibody escape, Antibody, Research Article
Abstract: We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence in vitro, and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutralization by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multiple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investigated was consistent with the lack of advantage observed in the clinical and experimental data. IMPORTANCE We observed repeated, independent emergence of mutations in the SARS-CoV-2 spike involving amino acids 1163 and 1167, within the HR2 functional motif. Conclusions derived from evolutionary and genomic diversity analysis suggest that the co-occurrence of both mutations might pose an advantage for the virus and therefore a threat to effective control of the epidemic. However, biological characterization, including in vitro experiments and analysis of clinical data, indicated no clear benefit in terms of stability or infectivity. In agreement with this, continuous epidemiological surveillance conducted months after the first observations revealed that both mutations did not successfully outcompete other variants and stopped circulating 9 months after their initial detection. Additionally, we evaluated the potential of both mutations to escape neutralizing antibodies, finding that the presence of these two mutations on their own is not likely to confer antibody escape. Our results provide an example of how newly emerged spike mutations can be assessed to better understand the risk posed by new variants and indicate that some spike mutations confer no clear advantage to the virus despite independently emerging multiple times and are eventually displaced by fitter variants., This work was funded by the Instituto de Salud Carlos III project COV20/00140 and COV20/00437, Spanish National Research Council project CSIC-COV19-021 and CSIC-COVID19-082, and the Generalitat Valenciana (SEJI/2019/011 and Covid_19-SCI). Action co-financed by the European Union through the Operational Program of the European Regional Development Fund (ERDF) of the Valencian Community 2014-2020. M.C. and R.G. are supported by Ramon y Cajal program from Ministerio de Ciencia.
Published: 2021

46. Evolutionary and Phenotypic Characterization of Two Spike Mutations in European Lineage 20E of SARS-CoV-2.

Author: Ruiz-Rodriguez P, Francés-Gómez C, Chiner-Oms Á, López MG, Jiménez-Serrano S, Cancino-Muñoz I, Ruiz-Hueso P, Torres-Puente M, Bracho MA, D'Auria G, Martinez-Priego L, Guerreiro M, Montero-Alonso M, Gómez MD, Piñana JL, González-Candelas F, Comas I, Marina A, Geller R, and Coscolla M
Subjects: Antibodies, Neutralizing immunology, COVID-19 virology, Europe, Genetic Variation, Genome, Viral, Humans, Neutralization Tests, SARS-CoV-2 immunology, Evolution, Molecular, Mutation, Phenotype, SARS-CoV-2 genetics, Spike Glycoprotein, Coronavirus genetics
Abstract: We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence in vitro , and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutralization by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multiple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investigated was consistent with the lack of advantage observed in the clinical and experimental data. IMPORTANCE We observed repeated, independent emergence of mutations in the SARS-CoV-2 spike involving amino acids 1163 and 1167, within the HR2 functional motif. Conclusions derived from evolutionary and genomic diversity analysis suggest that the co-occurrence of both mutations might pose an advantage for the virus and therefore a threat to effective control of the epidemic. However, biological characterization, including in vitro experiments and analysis of clinical data, indicated no clear benefit in terms of stability or infectivity. In agreement with this, continuous epidemiological surveillance conducted months after the first observations revealed that both mutations did not successfully outcompete other variants and stopped circulating 9 months after their initial detection. Additionally, we evaluated the potential of both mutations to escape neutralizing antibodies, finding that the presence of these two mutations on their own is not likely to confer antibody escape. Our results provide an example of how newly emerged spike mutations can be assessed to better understand the risk posed by new variants and indicate that some spike mutations confer no clear advantage to the virus despite independently emerging multiple times and are eventually displaced by fitter variants.
Published: 2021
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47. The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant.

Author: López MG, Chiner-Oms Á, García de Viedma D, Ruiz-Rodriguez P, Bracho MA, Cancino-Muñoz I, D'Auria G, de Marco G, García-González N, Goig GA, Gómez-Navarro I, Jiménez-Serrano S, Martinez-Priego L, Ruiz-Hueso P, Ruiz-Roldán L, Torres-Puente M, Alberola J, Albert E, Aranzamendi Zaldumbide M, Bea-Escudero MP, Boga JA, Bordoy AE, Canut-Blasco A, Carvajal A, Cilla Eguiluz G, Cordón Rodríguez ML, Costa-Alcalde JJ, de Toro M, de Toro Peinado I, Del Pozo JL, Duchêne S, Fernández-Pinero J, Fuster Escrivá B, Gimeno Cardona C, González Galán V, Gonzalo Jiménez N, Hernáez Crespo S, Herranz M, Lepe JA, López-Causapé C, López-Hontangas JL, Martín V, Martró E, Milagro Beamonte A, Montes Ros M, Moreno-Muñoz R, Navarro D, Navarro-Marí JM, Not A, Oliver A, Palop-Borrás B, Parra Grande M, Pedrosa-Corral I, Pérez González MC, Pérez-Lago L, Pérez-Ruiz M, Piñeiro Vázquez L, Rabella N, Rezusta A, Robles Fonseca L, Rodríguez-Villodres Á, Sanbonmatsu-Gámez S, Sicilia J, Soriano A, Tirado Balaguer MD, Torres I, Tristancho A, Marimón JM, Coscolla M, González-Candelas F, and Comas I
Subjects: COVID-19 virology, Communicable Disease Control methods, Humans, Incidence, Phylogeny, Physical Distancing, Quarantine methods, Quarantine organization & administration, SARS-CoV-2 classification, SARS-CoV-2 pathogenicity, Severity of Illness Index, Spain epidemiology, COVID-19 epidemiology, COVID-19 transmission, Communicable Disease Control organization & administration, Models, Statistical, SARS-CoV-2 genetics
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (R e < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2021
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48. A Mobile Health Application to Predict Postpartum Depression Based on Machine Learning.

Author: Jiménez-Serrano S, Tortajada S, and García-Gómez JM
Subjects: Adult, Female, Forecasting, Humans, Prospective Studies, Risk Factors, Sensitivity and Specificity, Surveys and Questionnaires, Depression, Postpartum etiology, Machine Learning, Telemedicine
Abstract: Background: Postpartum depression (PPD) is a disorder that often goes undiagnosed. The development of a screening program requires considerable and careful effort, where evidence-based decisions have to be taken in order to obtain an effective test with a high level of sensitivity and an acceptable specificity that is quick to perform, easy to interpret, culturally sensitive, and cost-effective. The purpose of this article is twofold: first, to develop classification models for detecting the risk of PPD during the first week after childbirth, thus enabling early intervention; and second, to develop a mobile health (m-health) application (app) for the Android(®) (Google, Mountain View, CA) platform based on the model with best performance for both mothers who have just given birth and clinicians who want to monitor their patient's test., Materials and Methods: A set of predictive models for estimating the risk of PPD was trained using machine learning techniques and data about postpartum women collected from seven Spanish hospitals. An internal evaluation was carried out using a hold-out strategy. An easy flowchart and architecture for designing the graphical user interface of the m-health app was followed., Results: Naive Bayes showed the best balance between sensitivity and specificity as a predictive model for PPD during the first week after delivery. It was integrated into the clinical decision support system for Android mobile apps., Conclusions: This approach can enable the early prediction and detection of PPD because it fulfills the conditions of an effective screening test with a high level of sensitivity and specificity that is quick to perform, easy to interpret, culturally sensitive, and cost-effective.
Published: 2015
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