Machine-learning analysis identifies “elite” viral controllers with increased survival and homeostatic responses in critical COVID-19

Nadia García-Mateo; Alejandro Álvaro-Meca; Tamara Postigo; Alicia Ortega; Amanda de la de la Fuente; Raquel Almansa; Noelia Jorge; Laura González-González; Lara Sánchez Recio; Isidoro Martínez; María Martín-Vicente; María José Muñoz-Gómez; Vicente Más; Mónica Vázquez; Olga Cano; Daniel Vélez-Serrano; Luis Tamayo; José Ángel Berezo; Rubén Herrán-Monge; Jesús Blanco; Pedro Enríquez; Pablo Ryan-Murua; Amalia de la Martínez de la Gándara; Covadonga Rodríguez; Gloria Andrade; Elena Bustamante-Munguira; Gloria Renedo Sánchez-Girón; Ramón Cicuendez Ávila; Juan Bustamante-Munguira; Wysali Trapiello; Elena Gallego Curto; Alejandro Úbeda-Iglesias; María Salgado-Villén; Enrique Berruguilla-Pérez; María del Carmen del de la Torre; Estel Güell; Fernando Casadiego; Ángel Estella; María Recuerda Núñez; Juan Manuel Sánchez Calvo; Sandra Campos-Fernández; Yhivian Peñasco-Martín; María Teresa García Unzueta; Ignacio Martínez Varela; María Teresa Bouza Vieiro; Felipe Pérez-García; Ana Moreno-Romero; Lorenzo Socias; Juan López Messa; Leire Pérez Bastida; Pablo Vidal-Cortés; Lorena del del Río-Carbajo; Jorge del Nieto del Olmo; Estefanía Prol-Silva; Víctor Sagredo Meneses; Noelia Albalá Martínez; Milagros González-Rivera; José Manuel Gómez; Nieves Carbonell; María Luisa Blasco; David de de Gonzalo-Calvo; Jessica González; Jesús Caballero; Carme Barberá; María Cruz Martín Delgado; Luis Jorge Valdivia; Caridad Martín-López; María Teresa Nieto; Ruth Noemí Jorge García; Emilio Maseda; Ana Loza-Vázquez; José María Eiros; Anna Motos; Laia Fernández-Barat; Joan Casenco-Ribas; Adrián Ceccato; Ferrán Barbé; David J. Kelvin; Jesús F. Bermejo-Martin; Ana P. Tedim; Salvador Resino; Antoni Torres

doi:10.1002/ctm2.70241

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (5) : e70241 DOI: 10.1002/ctm2.70241

LETTER TO THE JOURNAL

Machine-learning analysis identifies “elite” viral controllers with increased survival and homeostatic responses in critical COVID-19

Nadia García-Mateo ¹^,²
, Alejandro Álvaro-Meca ³^,⁴
, Tamara Postigo ¹
, Alicia Ortega ¹^,²
, Amanda de la de la Fuente ¹^,²
, Raquel Almansa ²^,⁵
, Noelia Jorge ²
, Laura González-González ²
, Lara Sánchez Recio ¹
, Isidoro Martínez ⁴^,⁶
, María Martín-Vicente ⁶
, María José Muñoz-Gómez ⁴^,⁶
, Vicente Más ⁶
, Mónica Vázquez ⁶
, Olga Cano ⁶
, Daniel Vélez-Serrano ⁷
, Luis Tamayo ²^,⁸
, José Ángel Berezo ²^,⁸
, Rubén Herrán-Monge ²^,⁸
, Jesús Blanco ⁸
, Pedro Enríquez ⁸
, Pablo Ryan-Murua ⁴^,⁹
, Amalia de la Martínez de la Gándara ¹⁰
, Covadonga Rodríguez ¹⁰
, Gloria Andrade ¹⁰
, Elena Bustamante-Munguira ²^,¹¹
, Gloria Renedo Sánchez-Girón ¹¹
, Ramón Cicuendez Ávila ¹¹
, Juan Bustamante-Munguira ¹²
, Wysali Trapiello ¹³
, Elena Gallego Curto ²^,¹⁴
, Alejandro Úbeda-Iglesias ¹⁵
, María Salgado-Villén ¹⁵
, Enrique Berruguilla-Pérez ¹⁶
, María del Carmen del de la Torre ¹⁷
, Estel Güell ¹⁷
, Fernando Casadiego ¹⁷
, Ángel Estella ¹⁸
, María Recuerda Núñez ¹⁸
, Juan Manuel Sánchez Calvo ¹⁹
, Sandra Campos-Fernández ²⁰
, Yhivian Peñasco-Martín ²⁰
, María Teresa García Unzueta ²¹
, Ignacio Martínez Varela ²²
, María Teresa Bouza Vieiro ²²
, Felipe Pérez-García ⁴^,²³^,²⁴
, Ana Moreno-Romero ²⁵
, Lorenzo Socias ²⁶
, Juan López Messa ²⁷
, Leire Pérez Bastida ²⁷
, Pablo Vidal-Cortés ²⁸
, Lorena del del Río-Carbajo ²⁸
, Jorge del Nieto del Olmo ²⁸
, Estefanía Prol-Silva ²⁸
, Víctor Sagredo Meneses ²⁹
, Noelia Albalá Martínez ²⁹
, Milagros González-Rivera ³⁰
, José Manuel Gómez ³¹
, Nieves Carbonell ³²
, María Luisa Blasco ³²
, David de de Gonzalo-Calvo ²^,³³
, Jessica González ²^,³³
, Jesús Caballero ³⁴
, Carme Barberá ³⁵
, María Cruz Martín Delgado ³⁶
, Luis Jorge Valdivia ³⁷
, Caridad Martín-López ³⁸
, María Teresa Nieto ³⁸
, Ruth Noemí Jorge García ³⁹
, Emilio Maseda ⁴⁰
, Ana Loza-Vázquez ⁴¹
, José María Eiros ⁴²
, Anna Motos ²^,⁴³
, Laia Fernández-Barat ²^,⁴³
, Joan Casenco-Ribas ⁴³
, Adrián Ceccato ²^,⁴⁴
, Ferrán Barbé ²^,³³
, David J. Kelvin ⁴⁵^,⁴⁶
, Jesús F. Bermejo-Martin ¹^,²^,⁴⁷
, Ana P. Tedim ¹^,²
, Salvador Resino ⁴^,⁶
, Antoni Torres ²^,⁴³

Author information +

¹. Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca (IBSAL), Gerencia Regional de Salud de Castilla y León, Salamanca, Spain

². Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

³. Department of Preventive Medicine and Public Health, Faculty of Health Science, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain

⁴. Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain

⁵. Department of Cellular Biology, Histology and Pharmacology, University of Valladolid, Valladolid, Spain

⁶. Viral Infection and Immunity Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain

⁷. Department of Statistics and Operations Research, Universidad Complutense de Madrid, Plaza de Ciencias, Madrid, Spain

⁸. Critical Care Medicine Service, Hospital Universitario Rio Hortega, Gerencia Regional de Salud de Castilla y León, Valladolid, Spain

⁹. Internal Medicine Service, Hospital Infanta Leonor, Madrid, Spain

¹⁰. Critical Care Medicine Service, Hospital Infanta Leonor, Avenida de la Gran Vía del Este, Madrid, Spain

¹¹. Critical Care Medicine Service, Hospital Clínico Universitario de Valladolid, Gerencia Regional de Salud de Castilla y León, Valladolid, Spain

¹². Cardiovascular Surgery Service, Hospital Clínico Universitario de Valladolid, Gerencia Regional de Salud de Castilla y León, Valladolid, Spain

¹³. Clinical Analysis Service, Hospital Clínico Universitario de Valladolid, Gerencia Regional de Salud de Castilla y León, Valladolid, Spain

¹⁴. Critical Care Medicine Service, Hospital San Pedro de Alcántara, Cáceres, Spain

¹⁵. Critical Care Medicine Service, Hospital Punta de Europa, Algeciras, Spain

¹⁶. Unidad de Gestión Clínica de Análisis Clínicos, Hospital Punta de Europa, Algeciras, Spain

¹⁷. Department of Intensive Care Medicine, Hospital de Mataró, Mataró, Barcelona, Spain

¹⁸. Intensive Care Unit, Hospital Universitario de Jerez, Departamento de Medicina, Universidad de Cádiz, INiBICA, Jerez de la Frontera, Spain

¹⁹. Microbiology Department, Hospital Universitario de Jerez, Jerez de la Frontera, Spain

²⁰. Critical Care Medicine Service, Hospital Universitario Marqués de Valdecilla, Santander, Spain

²¹. Servicio de Análisis Clínicos, Hospital Universitario Marqués de Valdecilla, Santander, Spain

²². Critical Care Department, Hospital Universitario Lucus Augustí, Lugo, Spain

²³. Clinical Microbiology Service, Hospital Universitario Príncipe de Asturias, Madrid, Spain

²⁴. Biomedicine and Biotechnology Department, Faculty of Medicine, Universidad de Alcalá, Madrid, Spain

²⁵. Clinical Analysis Service, Hospital Universitario Príncipe de Asturias, Madrid, Spain

²⁶. Intensive Care Unit, Hospital Universitario Son Llàtzer, Palma, Spain

²⁷. Critical Care Medicine Service, Complejo Asistencial Universitario de Palencia, Palencia, Spain

²⁸. Intensive Care Unit, Complejo Hospitalario Universitario de Ourense, Ourense, Spain

²⁹. Critical Care Medicine Service, Complejo Universitario Asistencial de Salamanca, Salamanca, Spain

³⁰. Clinical Biochemistry Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain

³¹. Critical Care Medicine Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain

³². Intensive Care Unit, Hospital Clínico Universitario de Valencia, Valencia, Spain

³³. Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, Institut de Recerca Biomèdica de Lleida, Lleida, Spain

³⁴. Critical Care Medicine Service, Hospital Universitari Arnau de Vilanova, Lleida, Spain

³⁵. Critical Care Medicine Service, Hospital Universitari de Santa Maria, Lleida, Spain

³⁶. Intensive Care Unit, Hospital Universitario de Torrejón, Universidad Francisco de Vitoria, Torrejón de Ardoz, Madrid, Spain

³⁷. Critical Care Medicine Service, Hospital Universitario de León, León, Spain

³⁸. Critical Care Medicine Service, Hospital General de Segovia, Segovia, Spain

³⁹. Intensive Care Department, Hospital Nuestra Señora de Gracia, Zaragoza, Spain

⁴⁰. Anesthesiology and Reanimation Service, Hospital Universitario de la Paz, Madrid, Spain

⁴¹. Critical Care Medicine Service, Hospital Universitario Nuestra Señora de Valme, Sevilla, Spain

⁴². Microbiology Service, Hospital Universitario Río Hortega, Gerencia Regional de Salud de Castilla y León, Valladolid, Spain

⁴³. Department of Pulmonology, Hospital Clinic de Barcelona, Institut D Investigacions August Pi I Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain

⁴⁴. Critical Care Center, Institut d'Investigació i Innovació Parc Taulí (I3PT), Hospital Universitari Sagrat Cor, Sabadell, Spain

⁴⁵. Department of Microbiology and Immunology, Faculty of Medicine, Canadian Center for Vaccinology (CCfV), Dalhousie University, Halifax, NS, Canada

⁴⁶. Laboratory of Immunity, Shantou University Medical College, Shantou, Guangdong, China

⁴⁷. Department of Medicine, Faculty of Medicine, Universidad de Salamanca, Salamanca, Spain

jfbermejo@usal.es

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Nadia García-Mateo, Alejandro Álvaro-Meca, Tamara Postigo, Alicia Ortega, Amanda de la de la Fuente, Raquel Almansa, Noelia Jorge, Laura González-González, Lara Sánchez Recio, Isidoro Martínez, María Martín-Vicente, María José Muñoz-Gómez, Vicente Más, Mónica Vázquez, Olga Cano, Daniel Vélez-Serrano, Luis Tamayo, José Ángel Berezo, Rubén Herrán-Monge, Jesús Blanco, Pedro Enríquez, Pablo Ryan-Murua, Amalia de la Martínez de la Gándara, Covadonga Rodríguez, Gloria Andrade, Elena Bustamante-Munguira, Gloria Renedo Sánchez-Girón, Ramón Cicuendez Ávila, Juan Bustamante-Munguira, Wysali Trapiello, Elena Gallego Curto, Alejandro Úbeda-Iglesias, María Salgado-Villén, Enrique Berruguilla-Pérez, María del Carmen del de la Torre, Estel Güell, Fernando Casadiego, Ángel Estella, María Recuerda Núñez, Juan Manuel Sánchez Calvo, Sandra Campos-Fernández, Yhivian Peñasco-Martín, María Teresa García Unzueta, Ignacio Martínez Varela, María Teresa Bouza Vieiro, Felipe Pérez-García, Ana Moreno-Romero, Lorenzo Socias, Juan López Messa, Leire Pérez Bastida, Pablo Vidal-Cortés, Lorena del del Río-Carbajo, Jorge del Nieto del Olmo, Estefanía Prol-Silva, Víctor Sagredo Meneses, Noelia Albalá Martínez, Milagros González-Rivera, José Manuel Gómez, Nieves Carbonell, María Luisa Blasco, David de de Gonzalo-Calvo, Jessica González, Jesús Caballero, Carme Barberá, María Cruz Martín Delgado, Luis Jorge Valdivia, Caridad Martín-López, María Teresa Nieto, Ruth Noemí Jorge García, Emilio Maseda, Ana Loza-Vázquez, José María Eiros, Anna Motos, Laia Fernández-Barat, Joan Casenco-Ribas, Adrián Ceccato, Ferrán Barbé, David J. Kelvin, Jesús F. Bermejo-Martin, Ana P. Tedim, Salvador Resino, Antoni Torres. Machine-learning analysis identifies “elite” viral controllers with increased survival and homeostatic responses in critical COVID-19. Clinical and Translational Medicine, 2025, 15(5): e70241 DOI:10.1002/ctm2.70241

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.