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1. Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS eventsResearch in context

Author

Javier Martínez-Sanz, Jorge Díaz-Álvarez, Marta Rosas, Raquel Ron, José Antonio Iribarren, Enrique Bernal, Félix Gutiérrez, Andrés Ruiz Sancho, Noemi Cabello, Julián Olalla, Santiago Moreno, Sergio Serrano-Villar, Inma Jarrín, David Dalmau, M. Luisa Navarro, M. Isabel González, Federico Garcia, Eva Poveda, Jose Antonio Iribarren, Rafael Rubio, Francesc Vidal, Juan Berenguer, Juan González, M. Ángeles Muñoz-Fernández, Inmaculada Jarrín, Cristina Moreno, Marta Rava, Rebeca Izquierdo, Elba Mauleón, Joaquín Portilla, Irene Portilla, Esperanza Merino, Gema García, Iván Agea, José Sánchez-Payá, Juan Carlos Rodríguez, Livia Giner, Sergio Reus, Vicente Boix, Diego Torrus, Verónica Pérez, Julia Portilla, Juan Luís Gómez, Jehovana Hernández, Ana López Lirola, Dácil García, Felicitas Díaz-Flores, M. Mar Alonso, Ricardo Pelazas, M. Remedios Alemán, Víctor Asensi, María Eugenia Rivas Carmenado, Tomás Suarez-Zarracina, Federico Pulido, Otilia Bisbal, M. Asunción Hernando, David Rial, María de Lagarde, Octavio Arce, Adriana Pinto, Laura Bermejo, Mireia Santacreu, Roser Navarro, Candela Gonzalez, M. José Aramburu, Xabier Camino, Miguel Ángel von Wichmann, Miguel Ángel Goenaga, M. Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Xabier Kortajarena, Ignacio Álvarez-Rodriguez, Leire Gil, Lourdes Martínez, Catalina Robledano, Mar Masiá, Sergio Padilla, Araceli Adsuar, Rafael Pascual, Marta Fernández, Antonio Galiana, José Alberto García, Xavier Barber, Vanessa Agullo, Javier Garcia Abellán, Reyes Pascual, Guillermo Telenti, Lucia Guillén, Ángela Botella, Roberto Muga, Arantza Sanvisens, Daniel Fuster, Isabel Gutierrez, Juan Carlos López, Margarita Ramírez, Belén Padilla, Paloma Gijón, Teresa Aldamiz-Echevarría, Francisco Tejerina, Cristina Diez, Leire Pérez, Chiara Fanciulli, Saray Corral, Anna Martí, Joaquín Peraire, Consuelo Viladés, Montserrat Vargas, Montserrat Olona, Anna Rull, Verónica Alba, Elena Yeregui, Jenifer Masip, Graciano García-Pardo, Frederic Gómez Bertomeu, Sonia Espineira, Marta Montero, Sandra Cuéllar, Marino Blanes, María Tasias, Eva Calabuig, Miguel Salavert, Juan Fernández, Inmaculada Segarra, Juan González-García, Ana Delgado, Francisco Arnalich, José Ramón Arribas, Jose Ignacio Bernardino, Juan Miguel Castro, Luis Escosa, Pedro Herranz, Victor Hontañón, Silvia García-Bujalance, Milagros García, Alicia González-Baeza, M. Luz Martín-Carbonero, Mario Mayoral, M. Jose Mellado, Rafael Esteban, Rocío Montejano, M. Luisa Montes, Victoria Moreno, Ignacio Pérez-Valero, Berta Rodés, Guadalupe Rúa, Talía Sainz, Elena Sendagorta, Eulalia Valencia, Carmen Busca, Joanna Cano, Julen Cardiñanos, Rosa de Miguel, Jose Ramón Blanco, Laura Pérez-Martínez, José Antonio Oteo, Valvanera Ibarra, Luis Metola, Mercedes Sanz, Piedad Arazo, Gloria Sampériz, Marina Martinez, Angels Jaén, Montse Sanmartí, Mireia Cairó, Javier Martinez-Lacasa, Pablo Velli, Roser Font, Mariona Xercavins, Noemí Alonso, Francesco Aiello, María Rivero, Beatriz Piérola, Maider Goikoetxea, María Gracia, Carlos Ibero, Estela Moreno, Jesús Repáraz, Gemma Navarro, Manel Cervantes Garcia, Sonia Calzado Isbert, Marta Navarro Vilasaro, Belen Lopez Garcia, Ignacio de los Santos, Alejandro de los Santos, Jesús Sanz, Lucio García-Fraile, Enrique Martín, Ildefonso Sánchez-Cerrillo, Marta Calvet, Ana Barrios, Azucena Bautista, Carmen Sáez, Marianela Ciudad, Ángela Gutiérrez, Santos del Campo, José Luis Casado, Fernando Dronda, Ana Moreno, M. Jesús Pérez, Sergio Serrano, Ma Jesús Vivancos, Alejandro Vallejo, Matilde Sanchez, Jose Antonio Pérez-Molina, José Manuel Hermida, Antonia Alcaraz, Joaquín Bravo, Ángeles Muñoz, Cristina Tomás, Mónica Martínez, M. Carmen Villalba, Federico García, Clara Martínez, José Hernández, Leopoldo Muñoz Medina, Marta Álvarez, Natalia Chueca, David Vinuesa, Adolfo de Salazar, Ana Fuentes, Emilio Guirao, Laura Viñuela, Andrés Ruiz-Sancho, Francisco Anguita, Jorge Del Romero, Montserrat Raposo, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi, Begoña Baza, Eva Orviz, Antonio Antela, Elena Losada, Melchor Riera, María Peñaranda, M. Angels Ribas, Antoni A. Campins, Mercedes Garcia-Gazalla, Francisco J. Fanjul, Javier Murillas, Francisco Homar, Helem H. Vilchez, Luisa Martin, Antoni Payeras, Jesús Santos, María López, Crisitina Gómez, Isabel Viciana, Rosario Palacios, Luis Fernando López-Cortés, Nuria Espinosa, Cristina Roca, Silvia Llaves, Juan Manuel Tiraboschi, Arkaitz Imaz, Ana Karina Silva, María Saumoy, Sofía Catalina Scévola, Adrián Curran, Vicenç Falcó, Jordi Navarro, Joaquin Burgos, Paula Suanzes, Jorge García, Vicente Descalzo, Patricia Álvarez, Bibiana Planas, Marta Sanchiz, Lucía Rodríguez, M José Sánchez, Javier Pérez, Alfonso del Arco, Javier de la Torre, José Luis Prada, Onofre Juan Martínez, Lorena Martinez, Francisco Jesús Vera, Josefina García, Begoña Alcaraz, Antonio Jesús Sánchez Guirao, Alvaro Mena, Angeles Castro, Berta Pernas, Pilar Vázquez, Soledad López, Sofía Ibarra, Guillermo García, Josu Mirena, Oscar Luis Ferrero, Josefina López, M. Mar Cámara, Mireia de la Peña, Miriam Lopez, Iñigo Lopez, Itxaso Lombide, Victor Polo, Joana de Miguel, Carlos Galera, Marian Fernández, Helena Albendin, Antonia Castillo, Asunción Iborra, Antonio Moreno, M. Angustias Merlos, Asunción Vidal, Concha Amador, Francisco Pasquau, Concepcion Gil, Jose Tomás Algado, Inés Suarez-García, Eduardo Malmierca, Patricia González-Ruano, M. Pilar Ruiz, José Francisco Pascual, Elena Sáez, Luz Balsalobre, M. Villa López, Mohamed Omar, Carmen Herrero, M. Amparo Gómez, Miguel Alberto de Zarraga, Desiré Pérez, Vicente Estrada, Nieves Sanz, Noemí Cabello, Jorge Vergas García, Maria Jose Núñez, Iñigo Sagastagoitia, Miguel Górgolas, Alfonso Cabello, Beatriz Álvarez, Laura Prieto, Irene Carrillo, José Sanz, Alberto Arranz, Cristina Hernández, María Novella, M. José Galindo, Ana Ferrer, Antonio Rivero Román, Inma Ruíz, Antonio Rivero Juárez, Pedro López, Isabel Machuca, Mario Frias, Ángela Camacho, Ignacio Pérez, Diana Corona, Miguel Cervero, Rafael Torres, Juan Antonio Pineda, Pilar Rincón, Juan Macías, Luis Miguel Real, Anais Corma, Alejandro Gonzalez-Serna, Alexandre Pérez, Luis Morano, Celia Miralles, Antonio Ocampo, Guillermo Pousada, Lucía Patiño, Carlos Dueñas, Sara Gutiérrez, Elena Tapia, Cristina Novoa, Xjoylin Egües, and Pablo Telleria

Subjects
HIV, Non-AIDS events, Neoplasia, Cardiovascular event, CD4/CD8 ratio, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

Published
2023
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2. Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

Author

Anita Y.M. Howe, Chaturaka Rodrigo, Evan B. Cunningham, Mark W. Douglas, Julia Dietz, Jason Grebely, Stephanie Popping, Javier Alejandro Sfalcin, Milosz Parczewski, Christoph Sarrazin, Adolfo de Salazar, Ana Fuentes, Murat Sayan, Josep Quer, Midori Kjellin, Hege Kileng, Orna Mor, Johan Lennerstrand, Slim Fourati, Velia Chiara Di Maio, Vladimir Chulanov, Jean-Michel Pawlotsky, P. Richard Harrigan, Francesca Ceccherini-Silberstein, Federico Garcia, Marianne Martinello, Gail Matthews, Fay Fabián Fernando, Juan I. Esteban, Beat Müllhaupt, Julian Schulze zur Wiesch, Peter Buggisch, Christoph Neumann-Haefelin, Thomas Berg, Christoph P. Berg, Jörn M. Schattenberg, Christophe Moreno, Rudolf Stauber, Andrew Lloyd, Gregory Dore, Tanya Applegate, Juan Ignacio, Damir Garcia-Cehic, Josep Gregori, Francisco Rodriguez-Frias, Ariadna Rando, Yael Gozlan, Mario Angelico, Massimo Andreoni, Sergio Babudieri, Ada Bertoli, Valeria Cento, Nicola Coppola, Antonio Craxì, Stefania Paolucci, Giustino Parruti, Caterina Pasquazzi, Carlo Federico Perno, Elisabetta Teti, C. Vironet, Anders Lannergård, Ann-Sofi Duberg, Soo Aleman, Tore Gutteberg, Alexandre Soulier, Aurélie Gourgeon, Stephane Chevaliez, Stanislas Pol, Fabrice Carrat, Dominique Salmon, Rolf Kaiser, Elena Knopes, Perpetua Gomes, Rob de Kneght, Bart Rijnders, Mario Poljak, Maja Lunar, Rafael Usubillaga, Carole Seguin_Devaux, Enoch Tay, Caroline Wilson, Dao Sen Wang, Jacob George, Jen Kok, Ana Belén Pérez, Natalia Chueca, Miguel García-Deltoro, Ana María Martínez-Sapiña, María Magdalena Lara-Pérez, Silvia García-Bujalance, Teresa Aldámiz-Echevarría, Francisco Jesús Vera-Méndez, Juan Antonio Pineda, Marta Casado, Juan Manuel Pascasio, Javier Salmerón, Juan Carlos Alados-Arboledas, Antonio Poyato, Francisco Téllez, Antonio Rivero-Juárez, Dolores Merino, María Jesús Vivancos-Gallego, José Miguel Rosales-Zábal, María Dolores Ocete, Miguel Ángel Simón, Pilar Rincón, Sergi Reus, Alberto De la Iglesia, Isabel García-Arata, Miguel Jiménez, Fernando Jiménez, José Hernández-Quero, Carlos Galera, Mohamed Omar Balghata, Joaquín Primo, Mar Masiá, Nuria Espinosa, Marcial Delgado, Miguel Ángel von-Wichmann, Antonio Collado, Jesús Santos, Carlos Mínguez, Felícitas Díaz-Flores, Elisa Fernández, Enrique Bernal, José De Juan, José Joaquín Antón, Mónica Vélez, Antonio Aguilera, Daniel Navarro, Juan Ignacio Arenas, Clotilde Fernández, María Dolores Espinosa, María José Ríos, Roberto Alonso, Carmen Hidalgo, Rosario Hernández, María Jesús Téllez, Francisco Javier Rodríguez, Pedro Antequera, Cristina Delgado, Patricia Martín, Javier Crespo, Berta Becerril, Oscar Pérez, Antonio García-Herola, José Montero, Carolina Freyre, Concepción Grau, Joaquin Cabezas, Miguel Jimenez, Manuel Alberto Macias Rodriguez, Cristina Quilez, Maria Rodriguez Pardo, Leopoldo Muñoz-Medina, and Blanca Figueruela

Subjects
RAS, HCV, DAA, virologic failure, NS5A, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.

Published
2022
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3. Prospective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections

Author

Gerardo Rojo-Marcos, José Miguel Rubio-Muñoz, Andrea Angheben, Stephane Jaureguiberry, Silvia García-Bujalance, Lina Rachele Tomasoni, Natalia Rodríguez-Valero, José Manuel Ruiz-Giardín, Joaquín Salas-Coronas, Juan Cuadros-González, Magdalena García-Rodríguez, Israel Molina-Romero, Rogelio López-Vélez, Federico Gobbi, María Calderón-Moreno, Esteban Martin-Echevarría, Matilde Elía-López, José Llovo-Taboada, and TropNet Plasmodium ovale investigator group

Subjects
Plasmodium ovale curtisi, Plasmodium ovale wallikeri, Comparative study, Thrombocytopenia, INR, Antimalarials, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Few previous retrospective studies suggest that Plasmodium ovale wallikeri seems to have a longer latency period and produces deeper thrombocytopaenia than Plasmodium ovale curtisi. Prospective studies were warranted to better assess interspecies differences. Methods Patients with imported P. ovale spp. infection diagnosed by thick or thin film, rapid diagnostic test (RDT) or polymerase chain reaction (PCR) were recruited between March 2014 and May 2017. All were confirmed by DNA isolation and classified as P. o. curtisi or P. o. wallikeri using partial sequencing of the ssrRNA gene. Epidemiological, analytical and clinical differences were analysed by statistical methods. Results A total of 79 samples (35 P. o. curtisi and 44 P. o. wallikeri) were correctly genotyped. Males predominate in wallikeri group (72.7%), whereas were 48.6% in curtisi group. Conversely, 74.3% of curtisi group were from patients of African ethnicity, whilst 52.3% of Caucasians were infected by P. o. wallikeri. After performing a multivariate analysis, more thrombocytopaenic patients (p = 0.022), a lower number of platelets (p = 0.015), a higher INR value (p = 0.041), and shorter latency in Caucasians (p = 0.034) were significantly seen in P. o. wallikeri. RDT sensitivity was 26.1% in P. o. curtisi and 42.4% in P. o. wallikeri. Nearly 20% of both species were diagnosed only by PCR. Total bilirubin over 3 mg/dL was found in three wallikeri cases. Two patients with curtisi infection had haemoglobin under 7 g/dL, one of them also with icterus. A wallikeri patient suffered from haemophagocytosis. Chemoprophylaxis failed in 14.8% and 35% of curtisi and wallikeri patients, respectively. All treated patients with various anti-malarials which included artesunate recovered. Diabetes mellitus was described in 5 patients (6.32%), 4 patients of wallikeri group and 1 curtisi. Conclusions Imported P. o. wallikeri infection may be more frequent in males and Caucasians. Malaria caused by P. o. wallikeri produces more thrombocytopaenia, a higher INR and shorter latency in Caucasians and suggests a more pathogenic species. Severe cases can be seen in both species. Chemoprophylaxis seems less effective in P. ovale spp. infection than in P. falciparum, but any anti-malarial drug is effective as initial treatment. Diabetes mellitus could be a risk factor for P. ovale spp. infection.

Published
2018
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4. Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Author

Evangelia-Georgia Kostaki, Andreas Flampouris, Timokratis Karamitros, Natalia Chueca, Marta Alvarez, Paz Casas, Belen Alejos, Angelos Hatzakis, Federico Garcia, Dimitrios Paraskevis, CoRIS, Santiago Moreno, Inma Jarrín, David Dalmau, Maria Luisa Navarro, Maria Isabel González, Jose Luis Blanco, Rafael Rubio, Jose Antonio Iribarren, Félix Gutiérrez, Francesc Vidal, Juan Berenguer, Juan González, Belén Alejos, Victoria Hernando, Cristina Moreno, Carlos Iniesta, Luis Miguel Garcia Sousa, Nieves Sanz Perez, M Ángeles Muñoz-Fernández, Isabel María García-Merino, Irene Consuegra Fernández, Coral Gómez Rico, Jorge Gallego de la Fuente, Paula Palau Concejo, Joaquín Portilla, Esperanza Merino, Sergio Reus, Vicente Boix, Livia Giner, Carmen Gadea, Irene Portilla, María Pampliega, Marcos Díez, Juan Carlos Rodríguez, José Sánchez-Payá, Juan Luis Gómez, Jehovana Hernández, María Remedios Alemán, María del Mar Alonso, María Inmaculada Hernández, Felicitas Díaz-Flores, Dácil García, Ricardo Pelazas, Ana López Lirola, José Sanz Moreno, Alberto Arranz Caso, Cristina Hernández Gutiérrez, María Novella Mena, Federico Pulido, Otilia Bisbal, Asunción Hernando, Lourdes Domínguez, David Rial Crestelo, Laura Bermejo, Mireia Santacreu, José Antonio Iribarren, Julio Arrizabalaga, María José Aramburu, Xabier Camino, Francisco Rodríguez-Arrondo, Miguel Ángel von Wichmann, Lidia Pascual Tomé, Miguel Ángel Goenaga, Ma Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Aitziber Lizardi, Xabier Kortajarena, Mar Masiá, Sergio Padilla, Andrés Navarro, Fernando Montolio, Catalina Robledano, Joan Gregori Colomé, Araceli Adsuar, Rafael Pascual, Marta Fernández, Elena García, José Alberto García, Xavier Barber, Juan Carlos López Bernaldo de Quirós, Isabel Gutiérrez, Margarita Ramírez, Belén Padilla, Paloma Gijón, Teresa Aldamiz-Echevarría, Francisco Tejerina, Francisco José Parras, Pascual Balsalobre, Cristina Diez, Leire Pérez Latorre, Joaquín Peraire, Consuelo Viladés, Sergio Veloso, Montserrat Vargas, Miguel López-Dupla, Montserrat Olona, Anna Rull, Esther Rodríguez-Gallego, Verónica Alba, Marta Montero Alonso, José López Aldeguer, Marino Blanes Juliá, María Tasias Pitarch, Iván Castro Hernández, Eva Calabuig Muñoz, Sandra Cuéllar Tovar, Miguel Salavert Lletí, Juan Fernández Navarro, Jose Miguel Molina, Juan González-garcia, Francisco Arnalich, José Ramón Arribas, Jose Ignacio Bernardino de la Serna, Juan Miguel Castro, Luis Escosa, Pedro Herranz, Victor Hontañón, Silvia García-Bujalance, Milagros García López-Hortelano, Alicia González-Baeza, Maria Luz Martín-Carbonero, Mario Mayoral, Maria Jose Mellado, Rafael Esteban Micán, Rocio Montejano, María Luisa Montes, Victoria Moreno, Ignacio Pérez-Valero, Berta Rodés, Talia Sainz, Elena Sendagorta, Natalia Stella Alcáriz, Eulalia Valencia, José Ramón Blanco, José Antonio Oteo, Valvanera Ibarra, Luis Metola, Mercedes Sanz, Laura Pérez-Martínez, Angels Jaén, Montse Sanmartí, Mireia Cairó, Javier Martinez-Lacasa, Pablo Velli, Roser Font, Mariona Xercavins, Noemí Alonso, Jesús Repáraz, María Gracia Ruiz de Alda, María Teresa de León Cano, Beatriz Pierola Ruiz de Galarreta, Ignacio de los Santos, Jesús Sanz Sanz, Ana Salas Aparicio, Cristina Sarriá Cepeda, Lucio Garcia-Fraile Fraile, Enrique Martín Gayo, José Luis Casado, Fernando Dronda, Ana Moreno, María Jesús Pérez Elías, Cristina Gómez Ayerbe, Carolina Gutiérrez, Nadia Madrid, Santos del Campo Terrón, Paloma Martí, Uxua Ansa, Sergio Serrano, María Jesús Vivancos, Enrique Bernal, Alfredo Cano, Antonia Alcaraz García, Joaquín Bravo Urbieta, Ángeles Muñoz, Maria Jose Alcaraz, Maria del Carmen Villalba, Federico García, José Hernández, Alejandro Peña, Leopoldo Muñoz, David Vinuesa, Clara Martinez-Montes, Fernando García, Carlos Guerrero-Beltran, Jorge Del Romero, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi, Antonio Antela, Elena Losada, Antonio Aguilera, Melchor Riera, María Peñaranda, María Leyes, Ma Angels Ribas, Antoni A Campins, Carmen Vidal, Francisco Fanjul, Javier Murillas, Francisco Homar, Jesús Santos, Crisitina Gómez Ayerbe, Isabel Viciana, Rosario Palacios, Carmen María González, Pompeyo Viciana, Nuria Espinosa, Luis Fernando López-Cortés, Daniel Podzamczer, Elena Ferrer, Arkaitz Imaz, Juan Tiraboschi, Ana Silva, María Saumoy, Julián Olalla, Alfonso del Arco, Javier de la torre, José Luis Prada, José María García de Lomas Guerrero, Javier Pérez Stachowski, Concepción Amador, Onofre Juan Martínez, Francisco Jesús Vera, Lorena Martínez, Josefina García, Begoña Alcaraz, Amaya Jimeno, Angeles Castro Iglesias, Berta Pernas Souto, Alvaro Mena de Cea, Carlos Galera, Helena Albendin, Aurora Pérez, Asunción Iborra, Antonio Moreno, Maria Angustias Merlos, Asunción Vidal, Inés Suárez-García, Eduardo Malmierca, Patricia González-Ruano, Dolores Martín Rodrigo, Mohamed Omar Mohamed-Balghata, Juan A Pineda, Juan Macías, Miguel Thomson, Elena Delgado, Sonia Benito, and Vanessa Montero

Subjects
HIV-1, CRF02_AG, Spain, regional dispersal, spatiotemporal characteristics, Microbiology, QR1-502
Abstract

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics.

Published
2019
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5. Prevalence of resistance associated substitutions and efficacy of baseline resistance-guided chronic hepatitis C treatment in Spain from the GEHEP-004 cohort.

Author

Ana Belén Pérez, Natalia Chueca, Juan Macías, Juan Antonio Pineda, Javier Salmerón, Antonio Rivero-Juárez, Carmen Hidalgo-Tenorio, María Dolores Espinosa, Francisco Téllez, Miguel Ángel Von-Wichmann, Mohamed Omar, Jesús Santos, José Hernández-Quero, José Joaquin Antón, Antonio Collado, Ana Belén Lozano, Miguel García-Deltoro, Marta Casado, Juan Manuel Pascasio, Aida Selfa, José Miguel Rosales, Alberto De la Iglesia, Juan Ignacio Arenas, Silvia García-Bujalance, María José Ríos, Enrique Bernal, Onofre Martínez, Antonio García-Herola, Mónica Vélez, Pilar Rincón, and Federico García

Subjects
Medicine, Science
Abstract

Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.

Published
2019
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6. Comparison of Imported Plasmodium ovale curtisi and P. ovale wallikeri Infections among Patients in Spain, 2005–2011

Author

Gerardo Rojo-Marcos, José Miguel Rubio-Muñoz, Germán Ramírez-Olivencia, Silvia García-Bujalance, Rosa Elcuaz-Romano, Marta Díaz-Menéndez, María Calderón, Isabel García-Bermejo, José Manuel Ruiz-Giardín, Francisco Jesús Merino-Fernández, Diego Torrús-Tendero, Alberto Delgado-Iribarren, Mónica Ribell-Bachs, Juan Arévalo-Serrano, and Juan Cuadros-González

Subjects
Plasmodium ovale curtisi, Plasmodium ovale wallikeri, imported malaria, epidemiology, clinical features, Spain, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Sequencing data from Plasmodium ovale genotypes co-circulating in multiple countries support the hypothesis that P. ovale curtisi and P. ovale wallikeri are 2 separate species. We conducted a multicenter, retrospective, comparative study in Spain of 21 patients who had imported P. ovale curtisi infections and 14 who had imported P. ovale wallikeri infections confirmed by PCR and gene sequencing during June 2005–December 2011. The only significant finding was more severe thrombocytopenia among patients with P. ovale wallikeri infection than among those with P. ovale curtisi infection (p = 0.031). However, we also found nonsignificant trends showing that patients with P. ovale wallikeri infection had shorter time from arrival in Spain to onset of symptoms, lower level of albumin, higher median maximum core temperature, and more markers of hemolysis than did those with P. ovale curtisi infection. Larger, prospective studies are needed to confirm these findings. Download MP3 Length: 1:27

Published
2014
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11. Asociación de crisis febriles e infección por enterovirus y parechovirus humano en urgencias pediátricas: estudio piloto

Author

Paula García Sánchez, María de la Calle, Silvia García Bujalance, Cristina Calvo Rey, and María Pilar Romero Gómez

Subjects
Pediatrics, medicine.medical_specialty, biology, business.industry, Pediatrics, Perinatology and Child Health, Parechovirus, Medicine, Enterovirus, business, medicine.disease_cause, biology.organism_classification
Published
2022
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12. Urinary Tract Infections in Hospitalized COVID-19 Patients, What’s Up, Doc?

Author

Beatriz Díaz Pollán, Gladys Virginia Guedez López, Paloma María García Clemente, María Jiménez González, Silvia García Bujalance, and María Rosa Gómez-Gil Mirá

Subjects
COVID-19, SARS-CoV-2, UTI, CAUTI, superinfection, coinfection, General Medicine, urologic and male genital diseases, female genital diseases and pregnancy complications
Abstract

The SARS-CoV-2 pandemic might have increased the risks of healthcare-associated infections (HAIs); however, several studies of HAI such as urinary tract infections (UTIs) and catheter-associated urinary tract infections (CAUTIs) have shown contradictory results. The aim of this study is to assess the clinical features of UTIs and bacterial isolates from urine samples of hospitalized COVID-19 patients. We conducted a retrospective observational study including 87 COVID-19 patients with UTIs admitted to our centre. Bacterial UTIs presented were 87: 9 (10.3%) community-acquired UTIs (coinfection group) and 78 (89.6%) hospital-acquired UTIs (superinfection group). In the coinfection group, the most frequent type was non-CAUTI with 5 (55.5%) patients; however, the most frequent UTI in the superinfection group was CAUTI, with 53 (67.9%) patients. The median number of days of hospitalization in coinfected patients was lower than superinfection patients: 13 (IQR 11, 23) vs. 34 days (IQR 23, 47) p < 0.006. All UTI patients admitted to ICU, 38 (43.7%), belonged to the superinfection group. The mortality rate was 26.4% (23/87), 22/23 in the superinfection group. The most common microorganisms were E. coli 27 (28.4%), E. faecalis 25 (26.3%) and E. faecium 20 (21.1%). There was an increased incidence of E. faecalis and E. faecium in UTIs as well as hospital-acquired UTIs. This can be related to urethral catheterization during hospitalization, UCI admissions and the number of days of hospitalization.

Published
2022
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13. Characteristics of patients with suspected COVID-19 pneumonia and repeatedly negative RT-PCR

Author

Paula Navarro-Carrera, Patricia Roces-Álvarez, Juan Carlos Ramos-Ramos, Dolores Montero, Itsaso Losantos, Beatriz Díaz-Pollán, and Silvia García Bujalance

Subjects
SARS-CoV-2, RT-PCR, serological response, General Materials Science, COVID-19 pneumonia, Research Articles
Abstract

Objectives. Challenges remain and there are still a sufficient number of cases with epidemiological, clinical features and radiological data suggestive of COVID-19 pneumonia that persist negative in their RT-PCR results. The aim of the study was to define the distinguishing characteristics between patients developing a serological response to SARS-CoV-2 and those who did not. Methods. RT-PCR tests used were TaqPath 2019-nCoV Assay Kit v1 (ORF-1ab, N and S genes) from Thermo Fisher Diagnostics and SARS-COV-2 Kit (N and E genes) from Vircell. Serological response was tested using the rapid SARS-CoV2 IgG/IgM Test Cassette from T and D Diagnostics Canada and CMC Medical Devices and Drugs, S.L, CE. Results. In this cross-sectional study, we included a cohort of 52 patients recruited from 31 March 2020 to 23 April 2020. Patients with positive serology had an older average age (73.29) compared to those who were negative (54.82) (P2 in 27 of 34 patients with positive serology were below 94% (P Conclusions. Clinical features and other biomarkers in a context of a positive serology can be considered crucial for diagnosis.

Published
2021

14. High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world

Author

Ana María Martínez-Sapiña, Concepción Grau, Maria Rios, Javier Crespo, Óscar Pérez, Elisa Fernández, Antonio Rivero-Juárez, Carlos Mínguez, Juan Carlos Alados-Arboledas, Miguel Jimenez, Joaquín Primo, Antonio Poyato, Juan Manuel Pascasio, Mónica Vélez, Natalia Chueca, Juan Arenas, Javier Salmerón, Berta Becerril, José Luis Montero, María Dolores Ocete, Clotilde Fernández, Marta Casado, Sergi Reus, Teresa Aldámiz-Echevarría, Carolina Freyre, Pedro Antequera, María Jesús Vivancos-Gallego, Carmen Hidalgo, Miguel Angel Simón, Cristina Delgado, Alberto de la Iglesia, Dolores Merino, Enrique Bernal, Mar Masiá, José Hernández-Quero, Daniel Navarro, Nuria Espinosa, Carlos Galera, Federico García, Ana Belén Pérez, Antonio Aguilera, Jesús Santos, Patricia Martín, Fernando Jiménez, María Jesús Téllez, José Miguel Rosales-Zábal, Silvia García-Bujalance, Juan A. Pineda, María Magdalena Lara-Pérez, Francisco Téllez, Marcial Delgado, Pilar Rincón, Francisco Javier Rodríguez, Roberto Alonso, José De Juan, Antonio García-Herola, María Dolores Espinosa, Antonio Collado, Francisco Jesús Vera-Méndez, Rosario Hernández, José Joaquin Antón, Miguel Ángel Von-Wichmann, Miguel García-Deltoro, Isabel García-Arata, Felicitas Diaz-Flores, Mohamed Omar Balghata, Instituto de Salud Carlos III, European Commission, Fundación Progreso y Salud, Junta de Andalucía, and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica

Subjects
Cyclopropanes, Male, 0301 basic medicine, Pyrrolidines, Sustained Virologic Response, Sofosbuvir, Resistance testing, Hepacivirus, Viral Nonstructural Proteins, Direct-acting antivirals, chemistry.chemical_compound, 0302 clinical medicine, Resistance-associated substitution, Anilides, Prospective Studies, Sulfonamides, education.field_of_study, Imidazoles, virus diseases, Valine, Hepatitis C, Middle Aged, Retreatment, HCV, Cohort, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, medicine.drug, Cohort study, RASs, medicine.medical_specialty, Genotype, Proline, Lactams, Macrocyclic, Voxilaprevir, Population, Antiviral Agents, 03 medical and health sciences, Internal medicine, Drug Resistance, Viral, Ribavirin, medicine, Humans, education, Fluorenes, Ritonavir, Hepatology, business.industry, medicine.disease, digestive system diseases, Regimen, 030104 developmental biology, Treatment failure, chemistry, Spain, Benzimidazoles, Carbamates, business
Abstract

GEHEP-004 Study Group: María Dolores Ocete, Miguel Ángel Simón, Pilar Rincón, Sergi Reus, Alberto De la Iglesia, Isabel García-Arata, Miguel Jiménez, Fernando Jiménez, José Hernández-Quero, Carlos Galera, Mohamed Omar Balghata, Joaquín Primo, Mar Masiá, Nuria Espinosa, Marcial Delgado, Miguel Ángel von-Wichmann, Antonio Collado, Jesús Santos, Carlos Mínguez, Felícitas Díaz-Flores, Elisa Fernández, Enrique Bernal, José De Juan, José Joaquín Antón, Mónica Vélez, Antonio Aguilera, Daniel Navarro, Juan Ignacio Arenas, Clotilde Fernández, María Dolores Espinosa, María José Ríos, Roberto Alonso, Carmen Hidalgo, Rosario Hernández, María Jesús Téllez, Francisco Javier Rodríguez, Pedro Antequera, Cristina Delgado, Patricia Martín, Javier Crespo, Berta Becerril, Óscar Pérez, Antonio García-Herola, José Montero, Carolina Freyre, Concepción Grau., [Background & Aims] Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available., [Methods] GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded., [Results] A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin., [Conclusions] In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited., [Lay summary] Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations., This work was supported in part by grants from Fondo de Investigación Sanitaria (www.isciii.es) (PI15/00713), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (www.redes/redes/inicio) (RD16/0025/0040), Fundación Progreso y Salud, Junta de Andalucia (http://www.juntadeandalucia.es/fundacionprogresoysalud/es) (PI-0411-2014), and GEHEP-SEIMC (GEHEP-004).

Published
2019
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15. Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study

Author

Jaime Fernández-Bujarrabal Villoslada, Beatriz Dietl Gómez-Luengo, Daniel Ortiz-Sánchez, José Ramón Blanco Ramos, Bartolomé Gómez-Arroyo, Martín Sebastián Ruiz Grinspan, Ester Sáez de Adana Arróniz, Daniel Daniel López, Judit Villar-García, Begoña De Dios García, Josefina García García, Nuria Rabella García, Ana Rodríguez-Revillas, Lydia Martín González, Mercedes San Franco, Elena Martinez Robles, Teresa González Alegre, Elena Morcillo Rodríguez, Oriol Gasch Blasi, Laura Prieto Pérez, Isabel Jiménez Martínez, Elena Isaba Ares, Ricardo Deza-Palacios, Helena Mendez del Sol, Melchor Riera Jaume, Mercedes Rodriguez-Gutiérrez, Daniel Podzamczer, Mikel Urroz, Luis Ramos Ruperto, María Paniagua, Sergio Alcolea-Batres, Mar Masiá Canuto, Rubén Soriano-Arroyo, Paloma Merino Amador, Berta Antón-Huguet, Gabriela Alcaraz, Pablo Ryan, Carlos Franco, Leyre Díez-Porres, Juan Carlos Figueiras, Sara Lidia Kamal, Mónica Hernández, Lorena Barrera-López, Germán Ramírez-Olivencia, Kapil Laxman Nanwani Nanwani, Alberto Oreja, Montserrat Laguno, José Javier Castrodeza Sanz, Belén Loeches Yagüe, Maria Vargas, Luis Eduardo López-Cortés, Isabel Gutiérrez, Sara Vela Berna, P. Martín, Miguel Pedromingo Kus, Jesús Sanz Sanz, Mº Antonia Sepúlveda Berrocal, Carmen Yera Bergua, Juan Cuadros González, Julen Cadiñanos Loidi, Josefa Serralta Buades, María Concepción Prados Sánchez, Francesca Gioia, Iris Pedrola Gorrea, Francisco Arnaiz de las Revillas, Xabier Kortajarena Urkola, Laia Lorenzo-Esteller, Ruth Bravo-Lizcano, Angel Iniesta, Sofía González-García, Belén Martínez López, Agustín Rojas-Vieyra, Concepción García García, Raquel Cavallé-Pulla, Lucía Gómez García, Alicia Herrero, Carlos Jesús Dueñas Gutiérrez, Loreto Vidaur Tello, Carmen Fernández-Capitán, Victoria Lo-Iacono García, Cecilia Gómez-Domínguez, Adalgisa Falcone, María José Ruiz Rodríguez, Arancha Castellano, Miquel Hortos Alsina, María Concepción Nuñez, María Luisa Fernández Vidal, Jésica Abadia Otero, Natalia Moya-González, Albert Sabater Gil, Pedro de la Oliva, Ylenia María Conde-Alonso, Laura Castelo Corral, José Mº García de Lomas Guerrero, Verónica Pérez-Blanco, Isabel San Juan, Martina Archinà, Júlia Sellarés, Juan Carlos Ramos, Cintia María Martínez Mateu, Belén Fernández-Puntero, Andrea Torrecillas-Mainez, Luis Falgueras López, Carlos Carpio-Segura, María Gandullo-Moro, Francisco Abellán Martínez, Cristina Díez, Pilar Martín Dávila, Silvia Gómez-Zorrilla, María Pilar García García, Renzo Tejada-Sorados, María Dolores del Toro, E. Álvarez-Rojas, Gema Muñiz, Lucía Cajuela, María Novella Mena, Estel Pons Viñas, Andrea Pérez Rodríguez, Benito Almirante, Mónica Gozalo, Patricia Girón De Velasco-Sada, Camilo Sanz Zamudio, Ángeles García Flores, Joaquín López-Contreras González, Blanca Fabre-Estremera, Pelayo Fernández Cidón, María Martínez-Redondo, Paula Alejandra Hernández-Liebo, Juan Herrero, Marta Duque-Alcorta, María Teresa García Morales, Concepción Amador Prous, Alex Soriano, Raquel Hernando Nieto, Raquel Álvarez Franco, Alfonso Cabello Úbeda, Luis Force Sanmartín, Laura Mao Martín, Daniel Prieto-Arribas, Mario Pérez-Butragueño, Pere Domingo Pedrol, Henar Serrano-Martín, Mónica Zubimendi, M. Rodríguez-Rubio, David Pujol-Pocull, Manuel García-Gutiérrez, Carlos Manrique de Lara, Lucy Abella Vázquez, Marta Navarro Vilasaró, Carlota Cascajares-Sanz, Berta Torres, Daniel Ceniza-Pena, Isidro Moreno Gómez-Limón, María Rodríguez Mahía, Alí Martakoush, Antonio Buño-Soto, Patricia Serrano de la Fuente, Claudia González Rico, Teresa Pedraz, Conchita Pérez-Jorge Peremarch, Elena Trigo Esteban, Rosana Rouco Esteves Marques, Juan Mora Delgado, Inés Pérez Zapata, Sandra Pérez-Recio, María Ángeles Domínguez, Manuel Cervantes García, Francisco Reinoso-Lozano, M. Martí De Gracia, Carmina Oltra, Beatriz Pérez-Monte Mínguez, Guillermina Bejarano-Redondo, Sara Heili Frades, María Paz García Butenegro, Miguel Torralba González de Suso, Elena Álvaro-Alonso, Víctor J Moreno Cuerda, Gonzalo Garzón, Marcelo Daltro-Lage, Alberto Serrano Martínez, José María Aguado, Mar Mosquera, Ruth Figueroa Cerón, Juan Carlos Martin Gutiérrez, Javier Oliver Ortega, Esteban Martínez, Cristina Gómez-Ayerbe, Nerea Carrasco Antón, María Carmen Fariñas Álvarez, José Antonio Ruiz, Justo Menéndez, Lucía Díaz, José L. Casado, Pilar Vizcarra, Javier Veganzones, Miguel Ángel Moran Rodríguez, Mercedes López-Martinez, Emilio Letang, Paloma Romero Gallego-Acho, Julia Vasquez-Manau, Alexander Rombauts, Marta Robledo del Prado, Luis Puente, Beatriz Alvarez, Juan Emilio Losa García, José Tomas Algado Rabasa, Rafael Torres Perea, Angélica Rivera-Núñez, Esther Expósito Palomo, Antonio J. Carcas, Lucía Platero-Dueñas, Irene Martín Rubio, Miguel Salavert Lletí, Claudia García-Vaz, Antonio Martínez-Verdasco, Jorge Díaz-Garzón, Javier Nieto Arana, Fernando Cadenas-Gota, Richard Rojas, Abelardo García de Lorenzo, Juan Carlos López, Pedro Luis Martinez Hernández, Manuela de Pablos-Gómez, Pablo Alonso, Enrique Seco, María García-López, Lorena López-Corcuer, Celia Blasco-Andres, Delia Romera-Cano, José M. Azcona Gutiérrez, Almudena Gutiérrez-Arroyo, Paula Mendoza Roy, Ignacio De los Santos Gil, Miguel Angel Sánchez-Castellano, Sara Medrano Pardo, Mikel del Álamo Martínez de Lagos, Rocío Martínez Avilés, Elisabet Martínez-Cerón, José Manuel Vázquez Comendador, Marta Virgós-Varela, Alejandra Álvarez Brandt, Carmen Herrero Rodríguez, Jorge Martínez Jordán, Antonio Rezusta López, Marta Vizcaíno Callejón, Manuela Simon-Velasco, Jorge Ignacio Alonso-Eiras, Elisa García Vázquez, Mercè Gurguí Ferrer, Mónica González Bardanca, Nataly Cancelliere-Fernández, José Luis Díaz de Tuesta del Arco, María Larrosa, Alejandro García García, Carmen Román-Hernández, Elena Calvin-García, José Sanz Moreno, Miguel Silvestre-Niño, Nieves Valcarce Pardeiro, Maria Teresa Corcuera-Pindado, Enrique Monteoliva, Aina Gabarrell Pascuet, Elena María Aranda Rife, Aina Gomila Grange, Alba Alastrué Violeta, Daniel Roger Zapata, Jaime Montserrat, Eduardo Malmierca Corral, Marco Palma, Blanca Martínez Cifre, Gema Domínguez de Pablos, Emilio Cuesta, Eva Perales, Silvia Hernáez Crespo, Juan Torres-Macho, Adrián Sánchez Montalvá, Rocío Montejano Sánchez, Eva Van den Eynde Otero, Silvia Castañeda Espinosa, Virginia Pérez Doñate, Adriana Hernández Belmonte, Laura Iglesias Llorente, María Sanz de Pedro, Juan Espinosa Pereiro, Lubna Dani Ben-Abdellah, Raquel Barrós González, Iván Piñero, Araceli López-Tofiño, Ana Such-Diaz, Karim Mohamed Ramírez, Pilar Toledano Sierra, Rebeca Izquierdo, Guillermo Cuevas, Andrés Felipe Cardona Arias, Ileana Gabriela-Tomoiu, David Vinuesa García, Ander González Sarria, Stephan Stuart, José María Fernández, Javier Torres-Cortés, Elisabet Delgado Sánchez, María Varela-Cerdeira, Gemma Bassani, Berta Román Bernal, Isabel García, Paula Betancort de la Torre, Yolanda Martínez-Abad, Beatriz Arizcun, Juan José Cabanillas-Martín, Guillermo Estrada Fernández, Oscar del Río Pérez, Inmaculada Martín Pérez, Andony García, Luis Gómez-Carrera, Alexander Agrifoglio, Alberto M. Borobia, Jordi Niubó, Vanessa Alende Castro, Lara Montes Andújar, Alexandra De la Vega, Efrén Sánchez Vidal, Isabel A. Pérez Hernández, Laura Frade-Pardo, Ana Josefa Tebar-Martinez, Silvia Álvarez Kaelis, Sara De la Fuente Moral, Luz Martin Carbonero, Juan Cantón De Seoane, María Dolores Montero-Vega, Juan Carlos Gainzarain Arana, Sergio España Cueto, Rocío Nuñez-Cabetas, María Sánchez-Martín, Constanza Muñoz Hornero, Ana Gómez-Zamora, Javier Díaz Luperena, Patricia González-Donapetry, José Miguel Cisneros, Lucía Hernández-Rivas, Patricia González Ruano, Andrea Espigares Correa, Rocío González-León, Nicolás García-Arenzana, Omar Cervera, Andrés Canut Blasco, Ana Isabel Cañabate, Mercedes Villarreal García-Lomas, Melania Íñigo Pestaña, Maria Álvarez de Castro, Ana Correa Ruiz, Belén Civantos, Lydia Pascual-García, Paula Villares Fernández, Mikel Rico-Briñas, María José Alcaide-Martín, Adoración Valiente, Victoria Arnalich-Montiel, Pilar Retamar, Jesús Mingorance, Eva María Romay Lema, Pablo Galindo-Ballesteros, M. Teresa Pérez-Rodríguez, Rosario Maria Torres Santos-Olmo, Inmaculada Pinilla, Elie Dahdouh, Beatriz Tejero-Soriano, Cristina Pizarro-Sanchez, Félix Gutiérrez Rodero, Luis Jara-Palomares, María Hernández-Gancedo, Cristina Chico Chumillas, Sergio Gilaberte Reyzábal, Manuel González-Viñolis, Ana Martínez Sapiña, Francisco Parras, Teresa Rubio Obanos, Iker Falces-Romero, Adriana Sánchez Serrano, Teresa Álvarez de Espejo Montiel, Jorge Valencia, Miquel Pujol, José Luis Velasco Garrido, Belén Calderón-Llopis, Álvaro Varela Plaza, Abel Caro, Juan José González-Garcia, Miguel Sampedro Núñez, María Fernández-Velilla, Emilio Cendejas-Bueno, María Cecilia Cánepa, José Luis Santiago Blanco, Alicia Rico-Nieto, Mónica Liébana Gómez, Sarah Caro Bragado, Susana Sánchez-Rico, José María Marimón Ortiz de Zárate, Paloma Dorao, Cristina Plaza-Moreno, Isabel Valbuena, Natividad Benito Hernández, Ginger Giorgiana Cabrera Tejada, Jordi Carratalà, Sara Fernández Rodríguez, Vicente Ferrer Díaz De Brito Fernández, Pilar Catalán, Pablo Mariscal-Aguilar, Germán Daroca-Bengoa, Rafael Fernandez, Raquel Casitas-Mateo, Ester Zamarrón de Lucas, Úrsula Quesada, Julio Yagüe, María Isabel Quijano Contreras, Trinidad Baselga-Puente, Lourdes Herrera Pacheco, Carlota Gudiol, Alazne Lartategi Iraurgi, Estefanía Martinez-Chavez, Silvia Valero Rovira, Alba Bergas, Zaida Ruiz de Azua, Teresa Prim, Cristina García-Quero, Pilar Hernández Machín, Rubén Gomez-Rioja, María Pavón-Masa, María de las Mercedes Valentín-Pastrana Aguilar, Ilduara Pintos Pascual, Lucía Brieba-Plata, María Jesús Domínguez Santalla, Francisco Javier Membrillo de Novales, Raúl Galera-Martínez, Ana Lérida Urteaga, Miguel Cervero, Alberto Mangas-Moro, José Hernández Quero, Teresa Sancho Bueso, María Angustias Quesada Simón, Luz Parra-Gordo, Sofía Díaz-Carrasco, Juan Carlos Abad Almendro, Andrés Javier Ruiz Fernández, Estíbaliz Molina Iturritza, Aurea Díez-Tascón, Yale Tung-Chen, Marta Rava, Carlos Villasante, Gabriel Gaspar Alonso-Vega, Clara Cabré-Verdiell Surribas, Esther Fraile Villarejo, Aida Gutiérrez García, Ana Robustillo-Rodela, Rafael Padrós Selma, Jesús Rodríguez-Baño, Frank Perdomo-García, Lydia de la Fuente Regaño, María del Mar Arenas-Miras, Cristina Rodríguez Roca, Blanca Montero-San Martín, Gema Crespo-Sánchez, Miguel Ramírez-Verdyguer, Alberto Diaz de Santiago, Marta Díaz Menéndez, María de la Luz Padilla Salazar, Silvia Arribas-Terradillos, Sadaf Zafar Iqubal-Mirza, Isabel Rábago Lorite, Belén Estébanez, Maite Ganchegui Aguirre, André Barbosa Ventura, Estefanía Fernandez-Cerezo, Maria Eulalia Valencia, Zaira R. Palacios-Baena, Beatriz Diaz Pollan, Lidia Martín, Sara Fabra-Cadenas, José Miguel Cantero-Escribano, Carmen Busca Arenzana, Emilia Guasch-Arévalo, Virginia Fernández Espinilla, Ainhoa Urrutia Losada, Oscar Noya González, Raquel Aranega, Alejandro Rodríguez Saenz de Urturi, María Jesús Jaras Hernandez, Charbel Maroun Eid, Marta Mora Rillo, Antonio Ramos Martínez, Meritxell Ortega Montoliu, Jose María Mostaza, Sonia García Calvo, Cristina Verdú, Celia Salamanca, Cristina Cervera Acedo, Mónica Martínez, Miren Urrestarazu Larrañag, Carmen Barroso Castro, Ivo Vives-Beltrán, Lorea Arteche Eguizabal, Ana Montero, Javier Balsa Vázquez, Amparo Perez-Garcia Morillón, Alejandra Pérez García, Isabel Pérez-Tamayo, Rafael Cantón Moreno, Antonio Marín-García, Inmaculada Jarrín, Núria Trullen, Ines Fernandez-Jimenez, Guillermo Ruiz-Carrascosa, Almudena Villa Martí, Jamil Cedeño, Marcos Díez Martínez, Carlos Lahoz, Lorena De la Mora, Javier Sánchez-Lora, Ana María Martínez-Virto, Irene Sanjosé Muñiz, Adrian Peña-Hidalgo, Cristina López Mestanza, Carola Gutiérrez, Ana Laila Qasem-Moreno, Irene Salvo García, Lucía Fernández de Orueta, Jorge Parra Ruiz, Sergio Pérez Pinto, Carlos García-Mochales Fortún, Esteban García de las Heras, Patricia González Muñiz, Mario Fernández-Ruiz, Anna Ferrer Santolaria, Olga Sánchez Pernaute, Julieta Latorre, Jesús Manzanares, Miguel Angel Martinez Gallego, Helena Notario, Ángel Rodríguez-Villodres, Eva Fernández-Bretón, Encarnación Moral Escudero, Mónica Sánchez-Santiuste, Carmen Martínez Cilleros, Ricardo Fernández Roblas, María Yllescas, Eva Soria-Alcaide, Marta Arsuaga Vicente, Marta Gómez-López, Regina Cabrera-Gamero, Natalia Carrasco Fons, Diana Piñar Cabezos, Begoña Sánchez-Sánchez, Francisca Garcia-Iglesias, Raquel Marín-Baselga, Alberto Arranz Caso, Virginia Guedez-López, Lucia Boix Palop, Íñigo Gredilla Zubiría, María Hidalgo-Sánchez, Laura López-Tappero Irazábal, José Ignacio Bernardino de la Serna, Javier Queiruga, Natalia Guadalupe Barrera-López, María López-Jodar, Jorge Calderón Parra, Diego Rodríguez-Álvarez, José Molina, María Luisa Montes, Beatriz Rodríguez-Alonso, Daniel Useros Brañas, Maria Gracia Liras-Hernández, Lucía Romero-Imaz, Nieves Jaén Sánchez, Marta Segovia-Amaro, Marta Vara, Maribel Zamora Cintas, Montaña Jiménez Álvaro, Alberto Moreno Fernandez, Asunción Díaz, Jordi Mancebo Cortés, Francisco Javier De Castro Vega, Álvaro Navarro Batet, Francisco Javier Sagra, Alexandre Pérez González, Luis Castro, Isabel Barrio López, Marta Ruiz-Alguero, Silvia Ossaba-Vélez, Alberto Martín-Vega, Maria Jesus Bustinduy Odriozola, Sivia Pastor-Yvorra, Nuria Espinosa, Elena Múñez Rubio, María E García-Leoni, Sandra Rosillo, Cristina Carbonell, Iván Navas Clemente, Paula Arriola Martínez, Marta Peña, Lucía Martínez de Soto, Roberto Mora-Corcovado, Alberto Iglesias-Sigüenza, Rocío Ruíz-Hueso, Elena Alvar, Pedro Camacho, Jesús Sojo-Dorado, Remedios Alemán Valls, Ines Ponz, Esmeralda Palmier Peláez, María Arcos Rueda, Guillermo Maestro de la Calle, Ramón Pérez Tanoira, Ana Martínez Vidal, Cristina Amodeo, Marina Pacheco Martínez-Atienza, Clara Muñoz Aguirre, Felipe Villar Álvarez, Giorgina Salgueiro, Xavier Sanz Salvador, César Pérez-Romero, Beatriz Álvarez Zapatero, Nelsa González-Aguado, Robert Torres Sánchez del Arco, Enrique Míguez Rey, Merce Sirisi, Xavier Bonfill Cosp, Marta Yagüe-Barrado, Elena Pérez-Costa, Sandra Casares, Eva Estirado, Jorge Alvarez Troncoso, Cristina Martín-Carrasco, Diana Sande Llovo, Melchor Álvarez de Mon Soto, Arantzazu Mera Fidalgo, Francisco Marqués-González, Agustín Valido-Morales, Luis Alberto Nieto Fernández del Campo, Helem Haydee Vilchez, María Rivas-Carmenado, Francisco Moreno, Ignacio Fernández-Fernández, Henar Calvo Sánchez, Ana González-Cordón, Isabel Fernández-Navarro, María Simón Sacristán, Eva Jiménez-González de Buitrago, M. Muñoz, María Laplaza-González, Rosa de Miguel Buckley, Marta Redondo-Gutierrez, Paula Santibáñez Sáenz, Raquel Martínez Goñi, Marta Rico Rodríguez, Carlos Toro-Rueda, Francisco Arnalich, Ana Santiago-Recuerda, Clara Soto Abanedes, María Dolores Herrero Mendoza, Aquilino Sanchez Purificación, Diego Franch Llasat, María Velasco Arribas, Alejandro Martín-Quirós, Jorge Alba Fernández, Elena Ramírez, Amparo López-Bernus, Marta Alvarado, María Rexach Fumaña, Martín Pilares-Barco, Carmen Liébana Martos, Yolanda Martínez Martínez, Nicolas Merchante Gutiérrez, Maria José Asensio, Ianire Virto Peña, Lucía Mejuto-Illade, María Angeles Martinez-López, Pilar López-Pirez, Alejandro Suárez, Cristóbal Manuel Rodríguez Leal, Sara Garcia-Bellido Ruiz, Jorge Guisández Martín, Lucia Cachafeiro, Pedro Gil Divasson, Almudena Quintás-Viqueira, Laura Currás-Sánchez, Alverio Seiz-Martinez, Mario Ruiz-Bastián, Juan José Menéndez, Jorge Orihuela Martín, María Dolores Nieto Martín, Cristina Arévalo, Rebeca Marinas, Susana Casas Rodríguez, Zuriñe Ortiz de Zárate Ibarra, Yolanda Posada Franco, Joan Gómez-Junyent, Ana María Garijo Saiz, Marina Alguacil-Guillén, Ana Alguacil, Esther Aznar Muñoz, Sara Bañón Escandell, Juan Salillas Hernando, Chiara Fanciulli, Rosa Gómez-Gil, Francisco García-Río, Moncef Belhassen-García, Belén Gutierrez Sancerni, Sonia Vega Molpeceres, Inés Suárez-García, Leire Pérez-Latorre, Elena Chamarro Martí, Carmen Rosario Herrero Gil, Belén Gutiérrez-Gutiérrez, Tatiana Mata Forte, Francesca Sánchez Martínez, Lucía Ramos Merino, Santiago Yus, Mº Ángeles Marcos, Susana Martínez-Álvarez, Alexy Inciarte, Manuel Quintana-Díaz, Lucía Serrá, Belén Alejos, Guillem Policarpo Torres, José Román Muñoz del Rey, Irene Blanco-Bartolomé, Alberto Bahamonde Carrasco, Victoria Hernando, Jhon Rojas, David Roa, María Ángeles Garcinuño, Aránzazu Villasante de la Puente, Patricia Pérez-Palacios, Jesús Ruiz Aragón, Valvanera Ibarra Cucalón, Lucía Ortega Enciso, Ismail Zakariya-Yousef Breval, Jorge Navarro López, Gema Barbeito Castiñeiras, Clara Sala Jofre, Nora Molina Torres, Manuel Poyato, Inmaculada Poquet Catala, Virginia Pomar Solchaga, María Pilar Romero-Gómez, Clara Hernández, Helena Mozas Moriñigo, Mercedes Guillamón Sánchez, Zineb Karroud, Arianna Catino, Violeta Ramos Sesma, Santos del Campo, Pilar Fernández-Calle, Ana Fernández Cruz, Fernando Salvador, Rosa Mayayo-Alvira, Pilar Barco Núñez, Ana Isabel Peláez Ballesta, Silvia Suárez Diaz, Beatriz María Sanjuan, Nora Izko Gartzia, Teresa Aldámiz-Echevarría, Cecilia Tortajada Alamilla, Pau Bosch-Nicolau, María del Mar Alonso Socas, Sonia Calzado Isbert, Jose R. Arribas, Juan Fernández-Lahera, Elizabet Petkova Saiz, Eva Jiménez, Gabriela Abelenda-Alonso, Alba Ribera Puig, Pascual Sanabria-Carretero, Sara Rodrigo González, Irene Díaz de la Torre, Tamara Manso Gómez, Carmen Sáez Barberá, Roi Suárez Gil, Paloma García-Clemente, Héctor Meijide Míguez, Elsa Izquierdo-García, Josune Goikoetxea Agirre, Olalla Martínez Macia, Jesús Santos González, Guillermo Jiménez Álvarez, Cristina Marcelo-Calvo, Javier Coy Coy, Isabel Arenas-Berenguer, Julio García Rodríguez, Natalia Yustas-Benitez, Sarai Quirós-Fernández, Marina Noguerol-Gutiérrez, María Adalid Moll, Iván Bloise-Sánchez, Mario José Rodriguez Dominguez, Elena Salamanca, Francisco Mora Gómez, Lucio García-Fraile, Pablo Millán, C Gutiérrez, Montserrat Rodríguez, José Antonio Oteo Revuelta, Joseba Portu Zapirain, Cristina Moreno, Irene Carrillo Acosta, Jorge Calvo, Ana Mariño Callejo, David Romero-Ribate, Blanca Alonso, Elena Muñoz del Val, Elena Resino Foz, Olaia Rodriguez-Fraga, Miguel Villamarín, Irene Amores-Hernández, Laura Muñoz López, Esther García Almodóvar, Ismael Casares Guerrero, Angélica Villanueva-Freije, Nuria Parra Arribas, Montserrat Sanmarti Vilamala, Macarena Lerín-Baratas, Mercedes Castro-Martínez, Melissa Carreres Candela, Lucia Suárez Pérez, Jose Manuel Iturzaeta-Sánchez, Thamires Silva-Freire, José Antonio Peregrina, María Luisa Machado Sicilia, Sergio Zurita, Daniel Molina Morant, Olga González-Peña, Fernando Lázaro-Perona, Paloma Oliver-Saez, Beatriz Mestre-Gómez, Luis Díaz Díez Picazo, Silvia García-Bujalance, Francisco Rodríguez Gómez, Pere Comas Casanova, Carlos Ruiz Martínez, Alberto Delgado-Iribarren, Berta Alonso-González, Isabel Moreno-Parra, Teresa Gómez-Ballesteros, Araceli Menéndez, Jose Manuel Añón, Ruth Jorge García, Jonathan Cámara Fernández, Miguel Górgolas Hernández-Mora, Itziar Diego Yagüe, Miriam Latorre-Millán, Covadonga Morcate Fernández, M. Río-García, Elisabet Lerma-Chippirraz, Carmen Yllera Gutiérrez, Francesc Albertí, Eva Flores, Carmen R. Uña Orejón, Patricio González-Pizarro, Neila Rodriguez-Roca, Miguel Fernández-Huerta, Inés Ferrer Ortiz, María José Blanco Vidal, Juan Pablo Avilés, Alicia Lorenzo Hernández, Mireia Puig Campmany, José Bravo-Ferrer, Gonzalo Martínez-Alés, Pablo Marguenda Contreras, M. Sánchez, Antonio García Pardo, Yolanda Meije, Francisco Tejerina, Carolina Hernández Carballo, Victoria Moreno, Daniel Laorden-Escudero, Ana Barrios Blandino, Alexia Costanza Espiño Álvarez, Ana Milagro Beamonte, Jerónimo Pachón, S San José-Villar, Marta Morando, María del Carmen Navarro Sáez, Rodolfo Álvarez-Sala Walther, Jon Ugalde Espiñeira, Fernando De la Calle Prieto, Nuria Fernández, Iván Pelegrín Senent, Alba Rueda López, Cristina Schüffelmann, Marcelino Hayek Peraza, Laura Labajo-Montero, Angel Robles Marhuenda, Pilar Durán, Ana Esteban-Romero, María Rosa Oltra Sempere, Ana Cosmen Sánchez, Alex Smithson Amat, Margarita Ramírez-Schacke, Marco Antonio Sempere Alcocer, Paloma Carrera-Vázquez, M Miarons, Teresa García Delange, Amelia Rodriguez-Mariblanca, Eva Talavera García, Roberto Vates Gómez, Óscar Sanz Peláez, José María Muñoz-Ramón, José Luis García Fogeda, Isabel Arroyo-Rico, Verónica Cano Llorente, Fernando González-Romo, Alberto Alonso-Babarro, Fátima Brañas, Fabricio Iannuccelli, Pilar Álvarez Padín, Luis Metola Sacristán, Vicente Boix, Víctor Hontañón, Juan Berenguer, José Luís Del Pozo León, Patricia Sorní Moreno, Maria Isabel Torres, Rafael Mican Rivera, Amparo Blasco Claramunt, Carmen Ardanuy, Aychel Elena Roura Piloto, María Ángeles Molina, Isabel Asschert Agüero, Julía Alvárez del Vayo, Consuelo García-Sánchez, Begoña Reche-Martínez, Guillermo Cuervo, Carlos Iniesta, María Antonia Gómez-Mendieta, Ana María Noblejas Mozo, Andres Bartrina-Tarrio, Carmen De la Higuera Arranz, Yeray Untoria Tabares, Andrés Enrique Suárez-Plaza, Jesús Frías, Paloma López-Arévalo, Irene María Llorente-Cortijo, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), and Fundación SEIMC-GESIDA

Subjects
Male, Prognostic variable, medicine.medical_specialty, Databases, Factual, Coronavirus disease 2019 (COVID-19), 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Aged, Retrospective Studies, Models, Statistical, SARS-CoV-2, business.industry, Mortality rate, COVID-19, Retrospective cohort study, Articles, Middle Aged, Prognosis, medicine.disease, Phenotype, Hospitals, Hospitalization, Logistic Models, Infectious Diseases, Spain, Cohort, Female, Lymphocytopenia, business, Cohort study
Abstract

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Published
2021

16. GEHEP 010 study: Prevalence and distribution of hepatitis B virus genotypes in Spain (2000-2016)

Author

Samuel Bernal, M. Basaras, María Dolores Ocete, Francisco Rodriguez-Frias, Maria Buti, Felipe Fernández-Cuenca, Avelina Suárez, Santiago Melón, Marta Álvarez, Antonio Orduña, Juan Luis Muñoz-Bellido, Isabel García-Arata, José Manuel Molina, Natalia Montiel, Silvia García-Bujalance, Rocio Trastoy, L. Nieto, Daniel Navarro de la Cruz, Federico García, Ana Fuentes, Antonio Aguilera, Ana Blazquez de Castro, Isabel Viciana, Gabriel Reina, and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, Hepatitis B virus, Sexual transmission, genetic structures, Genotype, 030106 microbiology, Distribution (economics), HIV Infections, Biology, Distribution, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, HBV, Prevalence, Humans, 030212 general & internal medicine, Retrospective Studies, Molecular epidemiology, business.industry, Transmission (medicine), Coinfection, virus diseases, Retrospective cohort study, Middle Aged, Hepatitis B, digestive system diseases, Infectious Diseases, Spain, Female, business, Demography
Abstract

[Objective] To study the prevalence and distribution of HBV genotypes in Spain for the period 2000–2016., [Methods] Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded., [Results] 1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR: 41–62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was: 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found., [Conclusions] We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups., This study has been funded in part by the funds of the research project GEHEP-2018-010, granted by the Hepatitis Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (Grupo de Hepatitis de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, GEHEP/SEIMC).

Published
2019

17. Surveillance of transmitted drug resistance to integrase inhibitors in Spain: implications for clinical practice

Author

CoRIS, Melchor Riera, J.L. Gómez-Sirvent, Nuria Espinosa, Joaquim Peraire, Julián Olalla, Natalia Chueca, Carlos Guerrero-Beltran, Silvia García-Bujalance, Mónica García-Álvarez, David Dalmau, Adrian Curran, David Vinuesa, Arkaitz Imaz, María J Pérez-Elías, Eva Poveda, Antonio Aguilera, José Ramón Blanco, Adolfo de Salazar, Paz Casas, Gemma Navarro, Irene Portilla, Félix Gutiérrez, Jesús Santos, Carlos Galera, Marta Álvarez, Carmen Rodríguez, José Miguel Molina, Federico García, Lucio García-Fraile, José Antonio Iribarren, and Beatriz Pierola

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, 030106 microbiology, Integrase inhibitor, HIV Infections, Drug resistance, Emtricitabine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Abacavir, Internal medicine, Drug Resistance, Viral, medicine, Prevalence, Humans, Pharmacology (medical), Public Health Surveillance, 030212 general & internal medicine, HIV Integrase Inhibitors, Aged, Pharmacology, Bictegravir, business.industry, Elvitegravir, Middle Aged, Raltegravir, Infectious Diseases, chemistry, Spain, Dolutegravir, HIV-1, Female, business, medicine.drug
Abstract

Background: Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART. Objectives: To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain. Methods: During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used. Results: Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/ lamivudine was 1.7%, 1.9% and 0.7%, respectively. Conclusions: Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.

Published
2019

18. Hepatitis with a multiple etiology in HIV-positive men who have sexual relations with other men

Author

M ª Eulalia Valencia Ortega, Silvia García Bujalance, and Juan González García

Subjects
Male, Pediatrics, medicine.medical_specialty, viruses, media_common.quotation_subject, medicine.disease_cause, Virus, 03 medical and health sciences, Sexual and Gender Minorities, 0302 clinical medicine, Hepatitis E virus, Risk Factors, Antiretroviral Therapy, Highly Active, HIV Seropositivity, Medicine, Humans, 030212 general & internal medicine, Homosexuality, lcsh:RC799-869, Homosexuality, Male, media_common, Hepatitis, business.industry, Gastroenterology, virus diseases, General Medicine, Hepatitis C, Hepatitis B, Middle Aged, Viral Load, medicine.disease, digestive system diseases, Hepatitis E, Etiology, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, business, Viral load
Abstract

Acute hepatitis C virus (HCV) is now a major health problem, mainly in men who have sexual relations with other men (MSM). Hepatitis E virus (HEV) causes sporadic cases of acute hepatitis. In this article, we describe two cases of acute hepatitis due to HCV with an interesting clinical progress.

Published
2017

20. Prevalence and distribution of hepatitis C virus genotypes in Spain during the 2000-2015 period (the GEHEP 005 study)

Author

Federico García, C. Guerrero, E. Coletta, M. J. Echevarria, M. Trigo, A. de la Iglesia, F. Fernández-Cuenca, Natalia Montiel, A. M. Martínez-Sapiña, Laura Cardeñoso, Elisa Martró, Isabel Viciana, Gabriel Reina, Antonio Aguilera, Silvia García-Bujalance, I. García-Arata, D. Ocete, M. J. Pena, P. Casas, Francisco Rodriguez-Frias, S. Pérez-Castro, J. Rodríguez-Granjer, M. C. Lozano, S. Bernal, D. Navarro, L. Benítez, M. J. Rodríguez, M. Rodríguez-Iglesias, Avelina Suárez, Juan Carlos Alados, and C. Vegas

Subjects
0301 basic medicine, hepatitis C virus, Adult, Male, medicine.medical_specialty, Genotype, Genotyping Techniques, Hepatitis C virus, genotype, 030106 microbiology, Parenteral transmission, prevalence, Distribution (economics), epidemiological, Hepacivirus, Biology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Virology, Epidemiology, medicine, geographical distribution, Prevalence, Humans, Aged, Retrospective Studies, Aged, 80 and over, Molecular Epidemiology, Hepatology, Molecular epidemiology, Transmission (medicine), business.industry, virus diseases, Hepatitis C, Chronic, Middle Aged, medicine.disease, Epidemiologic Studies, Phylogeography, Infectious Diseases, Spain, Coinfection, 030211 gastroenterology & hepatology, Female, business, Demography
Abstract

We report the largest study on the prevalence and distribution of HCV genotypes in Spain (2000-2015), and we relate them with clinical, epidemiological and virological factors. Patients from 29 hospitals in 10 autonomous communities (Andalusia, Aragon, Castilla-Leon, Catalonia, Galicia, Canary Islands, Madrid Community, Valencian Community, Murcia Region and Basque Country) have been studied. Annual distribution of HCV genotypes and subtypes, as well as gender, age, transmission route, HIV and/or HBV coinfection, and treatment details were recorded. We included 48595 chronically HCV-infected patients with the following characteristics: median age 51 years (IQR, 44-58), 67.9% male, 19.1% HIV-coinfected, 23.5% HBV-coinfected. Parenteral transmission route was the most frequent (58.7%). Genotype distribution was 66.9% GT1 (24.9% subtype 1a and 37.9% subtype 1b), 2.8% GT2, 17.3% GT3, 11.4% GT4 and 0.1% GT5 and 0.02% GT6. LiPA was the most widely HCV genotyping test used (52.4%). HCV subtype 1a and genotypes 3 and 4 were closely associated with male gender, parenteral route of infection and HIV and HBV coinfection; in contrast, subtype 1b and genotype 2 were associated with female gender, nonparenteral route and mono-infection. Age was related to genotype distribution, and different patterns of distribution and biodiversity index were observed between different geographical areas. Finally, we describe how treatment and changes in transmission routes may have affected HCV genotype prevalence and distribution patterns. We present the most recent data on molecular epidemiology of hepatitis C virus in Spain. This study confirms that genotype distributions vary with age, sex, HIV and HBV coinfection and within geographical areas and epidemiological groups.

Published
2016

21. Long-term control of HIV replication with dolutegravir and pegylated interferon alpha-2a in an HIV-infected patient with sixtuple-class resistance

Author

Jose R. Arribas, Ignacio Pérez-Valero, Silvia García-Bujalance, Jonathan M. Schapiro, and M. Luisa Montes

Subjects
business.industry, Immunology, Human immunodeficiency virus (HIV), medicine.disease_cause, Virology, chemistry.chemical_compound, Infectious Diseases, chemistry, Hiv infected, Pegylated interferon alpha 2a, Dolutegravir, Immunology and Allergy, Medicine, business, Long term control
Published
2014
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22. Comparison of ImportedPlasmodium ovale curtisiandP. ovale wallikeriInfections among Patients in Spain, 2005–2011

Author

Marta Díaz-Menéndez, Francisco Jesús Merino-Fernández, Germán Ramírez-Olivencia, Silvia García-Bujalance, José Miguel Rubio-Muñoz, Juan Cuadros-González, José Manuel Ruiz-Giardín, Mónica Ribell-Bachs, Diego Torrús-Tendero, Rosa Elcuaz-Romano, Gerardo Rojo-Marcos, Juan Arévalo-Serrano, María Calderón, Alberto Delgado-Iribarren, and Isabel García-Bermejo

Subjects
Male, Pediatrics, clinical features, Epidemiology, vector-borne infections, Plasmodium ovale, lcsh:Medicine, thrombocytopenia, Comorbidity, Plasmodium ovale curtisi, Genotype, Child, Prospective cohort study, digestive, oral, and skin physiology, Middle Aged, Severe thrombocytopenia, Infectious Diseases, Plasmodium ovale wallikeri, Female, imported malaria, Adult, Microbiology (medical), medicine.medical_specialty, Adolescent, Sequencing data, malaria, parasites, Core temperature, Biology, History, 21st Century, digestive system, lcsh:Infectious and parasitic diseases, Young Adult, stomatognathic system, Internal medicine, medicine, Humans, lcsh:RC109-216, Retrospective Studies, Research, lcsh:R, medicine.disease, biology.organism_classification, Thrombocytopenia, Malaria, Spain
Abstract

Sequencing data from Plasmodium ovale genotypes co-circulating in multiple countries support the hypothesis that P. ovale curtisi and P. ovale wallikeri are 2 separate species. We conducted a multicenter, retrospective, comparative study in Spain of 21 patients who had imported P. ovale curtisi infections and 14 who had imported P. ovale wallikeri infections confirmed by PCR and gene sequencing during June 2005-December 2011. The only significant finding was more severe thrombocytopenia among patients with P. ovale wallikeri infection than among those with P. ovale curtisi infection (p = 0.031). However, we also found nonsignificant trends showing that patients with P. ovale wallikeri infection had shorter time from arrival in Spain to onset of symptoms, lower level of albumin, higher median maximum core temperature, and more markers of hemolysis than did those with P. ovale curtisi infection. Larger, prospective studies are needed to confirm these findings. We thank Francisco Javier Vilar Izquierdo for his assistance in the translation and critical review of this manuscript.Dr Rojo-Marcos is a consultant in tropical and travel medicine with the Department of Internal Medicine, Príncipe de Asturias Uni-versity Hospital, Alcalá de Henares, Madrid, Spain. His research interests include malaria, leishmaniasis, schistosomiasis, imported tropical diseases, and social and health problems of immigration Sí

Published
2014
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23. [Control of Chagas disease in pregnant Latin-American women and her children]

Author

Francisco J, Merino, Rocío, Martínez-Ruiz, Iciar, Olabarrieta, Paloma, Merino, Silvia, García-Bujalance, Teresa, Gastañaga, and María, Flores-Chavez

Subjects
Adult, Infection Control, Consensus, Latin America, Endemic Diseases, Pregnancy, Trypanosoma cruzi, Infant, Newborn, Antibodies, Protozoan, Humans, Chagas Disease, Female
Abstract

Chagas disease is a chronic and systemic infection caused by Trypanosoma cruzi. According to estimates from WHO, 10 million people are affected by this parasite. In the last years, birthrate among the immigrant women from Latin America settled in the Comunidad Autónoma de Madrid has been increasing, and as T. cruzi can be transmitted from mother to child, in fact 11 cases of congenital Chagas disease have been confirmed. Therefore, the aim of this paper is encouraging improvements in the coverage of the anti-T. cruzi antibodies detection in pregnant women from endemic areas. By this strategy, an active search for infected pregnant women and early detection of her infected newborns could be conducted, and then an early specific treatment could be administrated. Thus, there could be an important contribution to the control of Chagas disease in non-endemic area.

Published
2013

24. Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation?

Author

Francisco Xavier Zamora, Jose R. Arribas, Jesús Mingorance, Miriam Estébanez, Ignacio Pérez-Valero, Natalia Stella-Ascariz, Jose I Bernardino, Alejandro Martín-Quirós, Guillermo Ruiz-Carrascoso, and Silvia García-Bujalance

Subjects
Adult, Male, Tenofovir, Genotype, Anti-HIV Agents, Immunology, Human immunodeficiency virus (HIV), Organophosphonates, Etravirine, medicine.disease_cause, Emtricitabine, Deoxycytidine, Drug Resistance, Multiple, Viral, HIV Seropositivity, Nitriles, medicine, Immunology and Allergy, Humans, business.industry, Adenine, Lysine, virus diseases, Virology, Pyridazines, Infectious Diseases, Pyrimidines, Virologic response, Mutation (genetic algorithm), Mutation, Genotypic resistance, HIV-1, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Female, Asparagine, business, medicine.drug
Abstract

We report long-term virologic response to etravirine and tenofovir/emtricitabine in four HIV-1-infected patients who had prior standard genotypic resistance testing showing an isolated K103N mutation (three acquired, one transmitted). In three patients tested, the K103N mutation was detected in cellular HIV-1 DNA whereas remaining suppressed on etravirine plus tenofovir/emtricitabine.

Published
2012

25. Imported Plasmodium falciparum malaria in HIV-infected patients: a report of two cases

Author

Silvia García-Bujalance, José M. Rubio, A. Gutierrez, Carolina Navarro-San Francisco, Jose R. Arribas, and UAM. Departamento de Medicina

Subjects
Adult, Male, Plasmodium falciparum, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Medicina, lcsh:RC955-962, Drug interaction, Case Report, HIV Infections, Biology, Parasitemia, lcsh:Infectious and parasitic diseases, law.invention, Antimalarials, Acquired immunodeficiency syndrome (AIDS), law, Internal medicine, parasitic diseases, medicine, Imported malaria, Humans, lcsh:RC109-216, Malaria, Falciparum, Travel, Sequence analysis, HIV, Middle Aged, medicine.disease, biology.organism_classification, Intensive care unit, CD4 Lymphocyte Count, Chronic infection, Infectious Diseases, Treatment Outcome, Parasitology, Chemoprophylaxis, Tropical medicine, Immunology, Malaria
Abstract

As HIV becomes a chronic infection, an increasing number of HIV-infected patients are travelling to malaria-endemic areas. Association of malaria with HIV/AIDS can be clinically severe. Severe falciparum malaria is a medical emergency that is associated with a high mortality, even when treated in an Intensive Care Unit. This article describes two cases of HIV-positive patients, who returned from malaria-endemic areas and presented a parasitaemia > 5% of erythrocytes and clinical signs of severe falciparum malaria, both with > 350 CD4 cell count/μl, absence of chemoprophylaxis and successful response. Factors like drug interactions and the possible implication of anti-malarial therapy bioavailability are all especially interesting in HIV-malaria co-infections.

Published
2012

26. Molecular Surveillance of HIV-1 in Madrid, Spain: a Phylogeographic Analysis ▿

Author

Laura Cardeñoso, Avelina Suárez, Carmen de Mendoza, Silvia García-Bujalance, Isabel García-Bermejo, Roberto Alonso, José María González-Alba, F. Portero, Rosa Garcia, Fernando González-Candelas, Juan Carlos Galán, África Holguín, Rafael Delgado, and Rosa Ana Picazo González

Subjects
medicine.medical_specialty, Genotype, media_common.quotation_subject, Immunology, Immigration, Molecular Sequence Data, Human immunodeficiency virus (HIV), HIV Infections, Biology, Destinations, medicine.disease_cause, Microbiology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Population Groups, law, Virology, Epidemiology, medicine, Prevalence, Cluster Analysis, Humans, 030212 general & internal medicine, 030304 developmental biology, media_common, Transients and Migrants, 0303 health sciences, Molecular Epidemiology, Molecular epidemiology, Sequence Analysis, DNA, 3. Good health, Phylogeography, Transmission (mechanics), Genetic Diversity and Evolution, Spain, pol Gene Products, Human Immunodeficiency Virus, Insect Science, Cohort, HIV-1, Demography
Abstract

The molecular epidemiology of HIV-1 is constantly changing, mainly as a result of human migratory flows and the high adaptive ability of the virus. In recent years, Spain has become one of Europe's main destinations for immigrants and one of the western European countries with the highest rates of HIV-positive patients. Using a phylogeographic approach, we have analyzed the relationship between HIV-1 variants detected in immigrant and native populations of the urban area of Madrid. Our project was based on two coincidental facts. First, resistance tests were extended to naïve and newly diagnosed patients, and second, the Spanish government legislated the provision of legal status to many immigrants. This allowed us to obtain a large data set ( n = 2,792) from 11 Madrid hospitals of viral pol sequences from the two populations, and with this unique material, we explored the impact of immigration in the epidemiological trends of HIV-1 variants circulating in the largest Spanish city. The prevalence of infections by non-B HIV-1 variants in the studied cohort was 9%, rising to 25% among native Spanish patients. Multiple transmission events involving different lineages and subsubtypes were observed in all the subtypes and recombinant forms studied. Our results also revealed strong social clustering among the most recent immigrant groups, such as Russians and Romanians, but not in those groups who have lived in Madrid for many years. Additionally, we document for the first time the presence of CRF47_BF and CRF38_BF in Europe, and a new BG recombinant form found in Spaniards and Africans is tentatively proposed. These results suggest that the HIV-1 epidemic will evolve toward a more complex epidemiological landscape.

Published
2011

27. Comparison between sequence analysis and a line probe assay for testing genotypic resistance of human immunodeficiency virus type 1 to antiretroviral drugs

Author

Juan González-García, A. Gutierrez, Jose R. Arribas, C. Ladrón de Guevara, and Silvia García-Bujalance

Subjects
Microbiology (medical), Genetics, Protease, Base Sequence, Genotype, Sequence analysis, Anti-HIV Agents, medicine.medical_treatment, Molecular Sequence Data, Sequence Analysis, DNA, Biology, biology.organism_classification, Virology, Reverse transcriptase, Virus, Lentivirus, Drug Resistance, Viral, medicine, HIV-1, Humans, Viral disease, Line Probe Assay, Nucleoside
Abstract

The purpose of this study was to compare a line probe assay (LiPA) with sequence analysis for the detection of mutations conferring resistance to nucleoside and non-nucleoside inhibitors in human immunodeficiency reverse transcriptase and protease inhibitors. The limitations for interpreting LiPA make it unacceptable for routine clinical practice.

Published
2005

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