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1. Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19

Author

Jesús F. Bermejo-Martin, Milagros González-Rivera, Raquel Almansa, Dariela Micheloud, Ana P. Tedim, Marta Domínguez-Gil, Salvador Resino, Marta Martín-Fernández, Pablo Ryan Murua, Felipe Pérez-García, Luis Tamayo, Raúl Lopez-Izquierdo, Elena Bustamante, César Aldecoa, José Manuel Gómez, Jesús Rico-Feijoo, Antonio Orduña, Raúl Méndez, Isabel Fernández Natal, Gregoria Megías, Montserrat González-Estecha, Demetrio Carriedo, Cristina Doncel, Noelia Jorge, Alicia Ortega, Amanda de la Fuente, Félix del Campo, José Antonio Fernández-Ratero, Wysali Trapiello, Paula González-Jiménez, Guadalupe Ruiz, Alyson A. Kelvin, Ali Toloue Ostadgavahi, Ruth Oneizat, Luz María Ruiz, Iria Miguéns, Esther Gargallo, Ioana Muñoz, Sara Pelegrin, Silvia Martín, Pablo García Olivares, Jamil Antonio Cedeño, Tomás Ruiz Albi, Carolina Puertas, Jose Ángel Berezo, Gloria Renedo, Rubén Herrán, Juan Bustamante-Munguira, Pedro Enríquez, Ramón Cicuendez, Jesús Blanco, Jesica Abadia, Julia Gómez Barquero, Nuria Mamolar, Natalia Blanca-López, Luis Jorge Valdivia, Belén Fernández Caso, María Ángeles Mantecón, Anna Motos, Laia Fernandez-Barat, Ricard Ferrer, Ferrán Barbé, Antoni Torres, Rosario Menéndez, José María Eiros, and David J. Kelvin

Subjects
SARS-CoV-2, Cytokine, Sepsis, COVID-19, Plasma, Rnaemia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p

Published
2020
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2. Key Factors Associated With Pulmonary Sequelae in the Follow-Up of Critically Ill COVID-19 Patients

Author

Cabello, María Aguilar, Alcaraz-Serrano, Victoria, Aldecoa, Cesar, Alegre, Cynthia, Calderón, Ángela Algaba, Álvarez, Sergio, Ruiz, Antonio Álvarez, Andrea, Ruth, Aparicio, Maria de Alba, Arrieta, Marta, Ayestarán, J. Ignacio, Badia, Joan Ramon, Badía, Mariona, Pravia, Orville Báez, Mariño, Ana Balan, Balsera, Begoña, Barbena, Laura, Barbeta, Enric, Bardi, Tommaso, Segade, Patricia Barral, Barroso, Marta, García, José Ángel Berezo, Bermejo, Jesus, Bigas, Judit, Blancas, Rafael, Cortés, María Luisa Blasco, Saera, María Bodi, Bofill, Neus, Vieiro, María Teresa Bouza, Bueno, Leticia, Bustamante-Munguira, Juan, Martínez, Cecilia del Busto, Hermoso, David Campi, Fernández, Sandra Campos, Cano, Iosune, Canseco, Joan, Fernández, Pablo Cardinal, García, Laura Carrión, Carvalho, Sulamita, Castellà, Manuel, Castellví, Andrea, Castro, Pedro, Centelles-Serrano, María José, Ávila, Ramon Cicuendez, Cillóniz, Catia, Clar, Luisa, Climent, Cristina, Codina, Jordi, Conde, Pamela, Contreras, Sofía, Parra, Raul de Frutos, Sánchez, Raul de Pablo, Mendoza, Diego De, Díaz, Yolanda, Vilas, María Digna Rivas, Moreno, Cristina Dólera, Dot, Irene, Giraudo, Pedro Enríquez, Arijón, Inés Esmorís, Monjo, Teresa Farre, Fernández, Javier, Ferrando, Carlos, Figueras, Albert, Espina, Lorena Forcelledo, Franquesa, Enric, Furro, Àngels, Gabarrus, Albert, Galbán, Cristóbal, García, Felipe, García, Beatriz, Prieto, Emilio García, Redruello, Carlos García, Sagastume, Amaia García, Castillo, Maria Luisa Gascón, Gomà, Gemma, Casal, Vanesa Gómez, Gómez, Silvia, Gonzalez, Carmen Gómez, Gordo, Federico, Gracia, Maria Pilar, Fernández, María José Gutierrez, Herraiz, Alba, Herrán-Monge, Rubén, Ibarz, Mercedes, Iglesias, Silvia, Janer, Maria Teresa, Jiménez, Gabriel, Díaz, Mar Juan, Kiarostami, Karsa, Álvarez, Juan I. Lazo, León, Miguel, López-Gavín, Alexandre, Guerrero, Desiree Macias, Herrera, Nuria Mamolar, Mendiluce, Rafael Mañez, Mantellini, Cecilia L., Naya, Gregorio Marco, Barcos, Iris Marco, Marcos, Pilar, Peis, Enrique Marmol, Cuadrado, Marta Martín, Delgado, María Cruz Martin, Vicente, Paula Martín, Martínez, María, Fernández, Carmen Eulalia Martínez, Juan, Maria Dolores Martínez, Palacios, Basilisa Martínez, Jimenez, Juan Fernando Masa, Masclans, Joan Ramon, Maseda, Emilio, Fernández, Eva María Menor, Banderas, Priscila Metora, Minguez, Olga, Miralbés, Mar, Monclou, Josman, Montejo-González, Juan Carlos, Montserrat, Neus, Aznar, María Mora, Morales, Dulce, Cano, Sara Guadalupe Moreno, Rodríguez, David Mosquera, Muñoz-Bermúdez, Rosana, Nicolás, José María, Bou, Ramon Nogue, Salinas, Rafaela Nogueras, Ocón, Marta, Ortega, Ana, Ossa, Sergio, Pagliarani, Pablo, Parrilla, Francisco, Pedregosa-Díaz, José, Bastida, Leire Pérez, Pérez, Purificación, Pérez-García, Felipe, Planelles, Gloria Pérez, Rubio, Eva Pérez, Laguna, David Pestaña, Prados, Javier, Pujol, Andrés, Coll, Núria Ramon, Sanchez-Giron, Gloria Renedo, Roche-Campo, Ferran, Rodriguez, Laura, Castro, Felipe Rodríguez de, Rodríguez, Silvia, Ruiz, Covadonga Rodríguez, Rubio, Jorge, López, Alberto Rubio, Ruiz-García, Ángela Leonor, Miralles, Miriam Ruiz, Murúa, Pablo Ryan, Paz, Eva Saborido, Degracia, Ana Salazar, Sanchez, Miguel, Sánchez, Ana, Chinesta, Susana Sancho, Santacoloma, Bitor, Sariñena, Maria Teresa, Pensado, Marta Segura, Serra, Lidia, Serra-Fortuny, Mireia, Lázaro, Ainhoa Serrano, Servià, Lluís, Soliva, Laura, Speziale, Carla, Tormos, Adrián, Torres, Mateu, Tranque-Liberal, Celia, Trefler, Sandra, Trujillano, Javier, Vaca, Rafaela, Val, Estela, Ruiz, Luis Valdivia, Vallverdú, Montserrat, Martin-Montalvo, Maria Van der Hofstadt, Adrio, Sabela Vara, Vázquez, Nil, Vengoechea, Javier, Vilà-Vilardel, Clara, Vilanova, Judit, Warrington, Tatiana Villada, Yang, Hua, Yang, Minlan, Zapatero, Ana, González, Jessica, de Batlle, Jordi, Benítez, Iván D., Torres, Gerard, Santisteve, Sally, Targa, Adriano D.S., Gort-Paniello, Clara, Moncusí-Moix, Anna, Aguilà, Maria, Seck, Fatty, Ceccato, Adrián, Ferrer, Ricard, Motos, Anna, Riera, Jordi, Fernández, Laia, Menéndez, Rosario, Lorente, José Ángel, Peñuelas, Oscar, Garcia-Gasulla, Dario, Peñasco, Yhivian, Ricart, Pilar, Abril Palomares, Elena, Aguilera, Luciano, Rodríguez, Alejandro, Boado Varela, Maria Victoria, Beteré, Belén, Pozo-Laderas, Juan Carlos, Solé-Violan, Jordi, Salvador-Adell, Inmaculada, Novo, Mariana Andrea, Barberán, José, Amaya Villar, Rosario, Garnacho-Montero, José, Gómez, José M., Blandino Ortiz, Aaron, Tamayo Lomas, Luis, Úbeda, Alejandro, Catalán-González, Mercedes, Sánchez-Miralles, Angel, Martínez Varela, Ignacio, Jorge García, Ruth Noemí, Franco, Nieves, Gumucio-Sanguino, Víctor D., Bustamante-Munguira, Elena, Valdivia, Luis Jorge, Caballero, Jesús, Gallego, Elena, Rodríguez, Covadonga, Castellanos-Ortega, Álvaro, Trenado, Josep, Marin-Corral, Judith, Albaiceta, Guillermo M., de la Torre, Maria del Carmen, Loza-Vázquez, Ana, Vidal, Pablo, Añón, Jose M., Carbajales Pérez, Cristina, Sagredo, Victor, Carbonell, Nieves, Socias, Lorenzo, Barberà, Carme, Estella, Angel, Diaz, Emili, de Gonzalo-Calvo, David, Torres, Antoni, and Barbé, Ferran

Published
2023
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3. Low anti‐SARS‐CoV‐2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID‐19 patients

Author

Rubén Herrán-Monge, Wysali Trapiello, Laia Fernández-Barat, Cristina Doncel, Milagros González-Rivera, Carolina Puertas, Marta Domínguez-Gil, Jesus F. Bermejo-Martin, María José Muñoz-Gómez, Elena Bustamante, Felipe Pérez-García, Ana P. Tedim, Pedro Enriquez, Isidoro Martínez, Jesús Rico-Feijoo, David J. Kelvin, Vicente Mas, María Martín-Vicente, Noelia Jorge, P. Olivares, José María Eiros, Raquel Almansa, Mónica Herrero Vázquez, Antoni Torres, Ferran Barbé, Cesar Aldecoa, Anna Motos, José Manuel Gómez, Gloria Renedo, Jose Ángel Berezo, Amanda de la Fuente, Salvador Resino, Alicia Ortega, Nuria Mamolar, Ramón Cicuendez, Juan Bustamante-Munguira, Jamil Antonio Cedeno, Silvia Martín, Luis Tamayo, and Ricard Ferrer

Subjects
Coronavirus disease 2019 (COVID-19), Critical Illness, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Antibodies, Viral, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, S Antibody, antigenaemia, Internal Medicine, Humans, antibodies, Medicine, 030212 general & internal medicine, Antigens, Viral, 030304 developmental biology, 0303 health sciences, Viral Components, biology, SARS-CoV-2, Critically ill, business.industry, Brief Report, COVID-19, mortality, 3. Good health, Icu admission, Viral replication, Immunology, biology.protein, RNA, Viral, RNA, Brief Reports, Antibody, business
Abstract

Background Anti‐SARS‐CoV‐2 S antibodies prevent viral replication. Critically ill COVID‐19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU‐COVID patients is unknown. Patients/Methods We studied the impact of anti‐SARS‐CoV‐2 S antibodies levels on survival, viral RNA‐load in plasma, and N‐antigenaemia in 92 COVID‐19 patients over ICU admission. Results Frequency of N‐antigenaemia was >2.5‐fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA‐load in plasma, representing a protective factor against mortality (Adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61]

Published
2021
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4. Remdesivir and survival outcomes in critically ill patients with COVID-19: A multicentre observational cohort study

Author

Gumucio-Sanguino, Víctor D., Mañez, Rafael, Solé-Violan, Jordi, de Castro, Felipe Rodríguez, Suarez-Sipmann, Fernando, García, Ruth Noemí Jorge, Aznar, María Mora, Torres, Mateu, Martinez, María, Alegre, Cynthia, Riera, Jordi, Contreras, Sofía, Pericas, Juan Manuel, Ferrer, Ricard, Caballero, Jesús, Trujillano, Javier, Vallverdú, Montse, León, Miguel, Badía, Mariona, Balsera, Begoña, Servià, Lluís, Vilanova, Judit, Rodríguez, Silvia, Montserrat, Neus, Iglesias, Silvia, Prados, Javier, Carvalho, Sula, Miralbés, Mar, Monclou, Josman, Jiménez, Gabriel, Codina, Jordi, Val, Estela, Pagliarani, Pablo, Rubio, Jorge, Morales, Dulce, Pujol, Andrés, Furro, Àngels, García, Beatriz, Torres, Gerard, Vengoechea, Javier, Gonzalo-Calvo, David de, González, Jessica, Gomez, Silvia, Gómez, José M., Franco, Nieves, Barberán, José, Albaiceta, Guillermo M, Espina, Lorena Forcelledo, Prieto, Emilio García, Vicente, Paula Martín, del Busto Martínez, Cecilia, Vidal-Cortés, Pablo, Garmendia, José Luis García, Cabello, María Aguilar, Fernández, Carmen Eulalia Martínez, Carbonell, Nieves, Cortés, María Luisa Blasco, Lázaro, Ainhoa Serrano, Díaz, Mar Juan, Ortiz, Aaron Blandino, Menendez, Rosario, Valdivia, Luis Jorge, Boado, María Victoria, Chinesta, Susana Sancho, del Carmen de la Torre, Maria, Varela, Ignacio Martínez, Vieiro, María Teresa Bouza, Arijón, Inés Esmorís, Hermoso, David Campi, Salinas, Rafaela Nogueras, Monjo, Teresa Farre, Bou, Ramon Nogue, Naya, Gregorio Marco, Barberà, Carme, Coll, Núria Ramon, Catalán-González, Mercedes, Montejo-González, Juan Carlos, Sanchez-Giron, Gloria Renedo, Bustamante-Munguira, Juan, Bustamante-Munguira, Elena, Avila, Ramon Cicuendez, Herrera, Nuria Mamolar, Almansa, Raquel, Ortega, Alicia, Bermejo-Martin, Jesús, Sagredo, Víctor, Añon, Jose, Agrifoglio, Alexander, Cachafeiro, Lucia, Maseda, Emilio, Socias, Lorenzo, Novo, Mariana Andrea, Figueras, Albert, Janer, Maria Teresa, Soliva, Laura, Ocón, Marta, Clar, Luisa, Ayestarán, J Ignacio, Peñasco, Yhivian, Fernández, Sandra Campos, Serra-Fortuny, Mireia, Forcadell-Ferreres, Eva, Salvador-Adell, Immaculada, Bofill, Neus, Adell-Serrano, Berta, Díaz, Josep Pedregosa, Casacuberta-Barberà, Núria, Urrelo-Cerrón, Luis, Piñol-Tena, Àngels, Roche-Campo, Ferran, de la Gándara, Amalia Martínez, Murúa, Pablo Ryan, Ruíz, Covadonga Rodríguez, García, Laura Carrión, Álvarez, Juan I Lazo, Lorente, José Ángel, Loza-Vázquez, Ana, Guerrero, Desire Macias, Huerta, Arturo, Tognetti, Daniel, Redruello, Carlos García, Rodríguez, David Mosquera, Fernández, Eva María Menor, Adrio, Sabela Vara, Casal, Vanesa Gómez, Pensado, Marta Segura, Vilas, María Digna Rivas, Sagastume, Amaia García, de Pablo Sánchez, Raul, Laguna, David Pestaña, Bardi, Tommaso, Villar, Rosario Amaya, Gonzalez, Carmen Gómez, Castillo, Maria Luisa Gascón, Garnacho-Montero, José, Cantón-Bulnes, María Luisa, Marin-Corral, Judith, Pérez, Cristina Carbajales, Masclans, Joan Ramon, Degracia, Ana Salazar, Bigas, Judit, Muñoz-Bermúdez, Rosana, Vilà-Vilardel, Clara, Parrilla, Francisco, Dot, Irene, Zapatero, Ana, Díaz, Yolanda, Gracia, María Pilar, Pérez, Purificación, Castellví, Andrea, Climent, Cristina, Serra, Lidia, Barbena, Laura, Cano, Iosune, Ricart, Pilar, Herraiz, Alba, Marcos, Pilar, Rodríguez, Laura, Sariñena, Maria Teresa, Sánchez, Ana, Úbeda, Alejandro, Delgado, María Cruz Martin, Gallego, Elena, Jimenez, Juan Fernando Masa, Gomà, Gemma, Díaz, Emi, Ibarz, Mercedes, De Mendoza, Diego, Barbeta, Enric, Alcaraz-Serrano, Victoria, Badia, Joan Ramon, Castella, Manuel, Bueno, Leticia, Ceccato, Adrian, Palomeque, Andrea, Barat, Laia Fernandez, Cillóniz, Catia, Conde, Pamela, Fernández, Javier, Gabarrus, Albert, Kiarostami, Karsa, López-Gavín, Alexandre, Mantellini, Cecilia L, Speziale, Carla, Vázquez, Nil, Yang, Hua, Yang, Minlan, Ferrando, Carlos, Castro, Pedro, Arrieta, Marta, Nicolas, Jose Maria, Andrea, Rut, Barroso, Marta, Pérez, Raquel, Álvarez, Sergio, Garcia-Gasulla, Dario, Tormos, Adrián, Lomas, Luis Tamayo, Aldecoa, Cesar, Herrán-Monge, Rubén, García, José Ángel Berezo, Giraudo, Pedro Enríquez, Fernández, Pablo Cardinal, López, Alberto Rubio, Pravia, Orville Báez, Messa, Juan López, Bastida, Leire Pérez, Ruiz, Antonjo Alvarez, Trenado, José, Pous, Anna Parera, Galbán, Cristóbal, Lago, Ana López, Paz, Eva Saborido, Segade, Patricia Barral, Mariño, Ana Balan, Mendez, Manuel Valledor, de Frutos, Raúl, Aguilera, Luciano, Pérez-García, Felipe, López-Ramos, Esther, Ruiz-García, Ángela Leonor, Beteré, Belén, Blancas, Rafael, Dólera, Cristina, Planelles, Gloria Perez, Peis, Enrique Marmol, Juan, Maria Dolores Martinez, Miralles, Miriam Ruiz, Rubio, Eva Perez, Martin-Montalvo, Maria Van der Hofstadt, Sánchez-Miralles, Ángel, Warrington, Tatiana Villada, Pozo-Laderas, Juan Carlos, Estrella, Angel, Cano, Sara Guadalupe Moreno, Gordo, Federico, Palacios, Basilisa Martinez, Nieto, Maite, Nieto, Maria Teresa, Ossa, Sergio, Ortega, Ana, Sanchez, Miguel, Santacoloma, Bitor, Motos, Anna, Castañeda, Tatiana, Gabarrús, Albert, Barbé, Ferran, and Torres, Antoni

Published
2023
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5. Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients

Author

Raquel Almansa, Felipe Pérez-García, P. Olivares, José María Eiros, Ruben Herran, Jamil Antonio Cedeno, Anna Motos, Antoni Torres, Ferran Barbé, Salvador Resino, Marta Domínguez-Gil, Alicia Ortega, Gloria Renedo, Mónica Herrero Vázquez, Milagros González-Rivera, Amanda de la Fuente, María José Muñoz-Gómez, Elena Bustamante, Ricard Ferrer, Laia Fernández-Barat, María Martín-Vicente, Nuria Mamolar, Carolina Puertas, Jesus F. Bermejo-Martin, Jose Ángel Berezo, Cesar Aldecoa, Juan Bustamante-Munguira, Ana P. Tedim, Isidoro Martínez, Noelia Jorge, Jesús Rico-Feijoo, David J. Kelvin, Pedro Enriquez, Luis Tamayo, Vicente Mas, Ramón Cicuendez, José Manuel Gómez, and Silvia Martín

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), biology, business.industry, Proportional hazards model, Gastroenterology, Icu admission, Polyclonal antibodies, Internal medicine, Monoclonal, biology.protein, Risk of mortality, Medicine, Antibody, business, Viral load
Abstract

Purposeto evaluate the association between anti-SARS-CoV-2 S IgM and IgG antibodies with viral RNA load in plasma, the frequency of antigenemia and with the risk of mortality in critically ill patients with COVID-19.Methodsanti-SARS-CoV-2 S antibodies levels, viral RNA load and antigenemia were profiled in plasma of 92 adult patients in the first 24 hours following ICU admission. The impact of these variables on 30-day mortality was assessed by using Kaplan-Meier curves and multivariate Cox regression analysis.Resultsnon survivors showed more frequently absence of anti-SARS-CoV-2 S IgG and IgM antibodies than survivors (26.3% vs 5.6% for IgM and 18.4% vs 5.6% for IgG), and a higher frequency of antigenemia (47.4% vs 22.2%) (p p]: [S IgM (AUC ≥60): 0.48 (0.24; 0.97), 0.040]; [S IgG (AUC ≥237): 0.47 (0.23; 0.97), 0.042]; [Antigenemia (+): 2.45 (1.27; 4.71), 0.007]; [N1 viral load (≥ 2.156 copies/mL): 2.21 (1.11; 4.39),0.024]; [N2 viral load (≥ 3.035 copies/mL): 2.32 (1.16; 4.63), 0.017]. Frequency of antigenemia was >2.5-fold higher in patients with absence of antibodies. Levels of anti-SARS-CoV-2 S antibodies correlated inversely with viral RNA load.Conclusionabsence / insufficient levels of anti-SARS-CoV-2 S antibodies following ICU admission is associated to poor viral control, evidenced by increased viral RNA loads in plasma, higher frequency of antigenemia, and also to increased 30-day mortality.Take-home messageabsent or low levels of antibodies against the S protein of SARS-CoV- 2 at ICU admission is associated to an increased risk of mortality, higher frequency of antigenemia and higher viral RNA loads in plasma. Profiling anti-SARS-CoV-2 s antibodies at ICU admission could help to predict outcome and to better identify those patients potentially deserving replacement treatment with monoclonal or polyclonal antibodies.

Published
2021
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6. Viral Infection is Associated with an Increased Proinflammatory Response in Chronic Obstructive Pulmonary Disease

Author

Carlos Disdier, Ignacio Martin-Loeches, Felipe Bobillo, Alicia San Jose, Raúl Ortiz de Lejarazu, Agueda Herrero, Irene Rodriguez, Jesús Blanco, Mar Justel, Raquel Almansa, Vicente Roig, Angel Estella, Milagros del Olmo, Jesus F. Bermejo-Martin, Monica Sanchez-Garcia, Lucia Rico, Lorenzo Socias, David Andaluz-Ojeda, José María Eiros, Jose Ángel Berezo, and Sara Rosich

Subjects
Male, Exacerbation, medicine.medical_treatment, Immunology, law.invention, Proinflammatory cytokine, Pathogenesis, Pulmonary Disease, Chronic Obstructive, law, Virology, medicine, Humans, Aged, Aged, 80 and over, Inflammation, COPD, business.industry, Bacterial Infections, Middle Aged, medicine.disease, Intensive care unit, Pneumonia, Cytokine, Virus Diseases, Cytokines, Molecular Medicine, Respiratory virus, Female, business
Abstract

The development of new diagnostic methods based on molecular biology has led to evidence of the important role of respiratory viruses in chronic obstructive pulmonary disease (COPD) exacerbations. Cytokines and chemokines are recognized as key actors in the pathogenesis of COPD. The objective of this study was to evaluate the association between viral infection and host cytokine responses in 57 COPD patients hospitalized with an acute exacerbation. Seventeen cytokines were profiled using a Luminex-Biorad multiplex assay in plasma samples collected in the first 24 h following hospital admission. Stepwise linear regression analysis was performed, taking into account the influence of seven potential confounding factors in the results. Twenty-four out of 57 showed radiological signs of community-acquired pneumonia (CAP) at hospital admission, 25 patients required admission to the intensive care unit (ICU), 20 had a bacterial infection, and 20 showed a detectable respiratory virus in pharyngeal swabs. Regression analysis showed that viral infection correlated with higher levels of interleukin-6 (IL-6) (log value of the coefficient of regression B, p=0.47, 0.044), and monocyte chemoattractant protein-1 (MCP-1) (p=0.43, 0.019), and increased admission to the ICU. Viral infection also correlated with higher levels of interferon-γ (IFN-γ) (p=0.70, 0.026), which, in turn, was inversely associated with the severity of illness. Finally, viral infection was independently associated with higher levels of tumor necrosis factor-α (TNF-α) (p=0.40, 0.002). Thus our study demonstrates that in patients with COPD exacerbations, viral infection is directly associated with higher systemic levels of cytokines central to the development of the antiviral response, which are also known to contribute to inflammation-mediated tissue damage. These results reveal a potential specific role of viral infection in the pathogenesis of COPD exacerbations.

Published
2012
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7. IgM levels in plasma predict outcome in severe pandemic influenza

Author

Cristóbal León, Jordi Vallés, Ana Loza, Antoni Torres, Silvia Rojo, Victoria Fernández, Cristina López-Mestanza, Raúl Ortiz de Lejarazu, Leonor Nogales, Ignacio Martin-Loeches, Jesús Blanco, Catia Cilloniz, Lorenzo Socias, Angel Estella, Maria C Gallegos, Jesus F. Bermejo-Martin, Mar Justel, Sara Rosich, Raquel Almansa, Monica Gordon, Jose Ángel Berezo, David Andaluz-Ojeda, and Paula Ramirez

Subjects
Adult, Male, medicine.medical_treatment, viruses, Critical Illness, macromolecular substances, Immunoglobulin E, Antibodies, Viral, Severity of Illness Index, Virus, law.invention, Plasma, Influenza A Virus, H1N1 Subtype, Community-acquired pneumonia, law, Virology, Influenza, Human, medicine, Humans, Aged, COPD, biology, Proportional hazards model, business.industry, virus diseases, Immunosuppression, CAP, COPD, Critical, Cytokines, HBP, ICU, Immunoglobulins, Influenza, Prognosis, chronic obstructive pulmonary disease, community acquired pneumonia, high blood pressure, intensive care unit, Pneumonia, Middle Aged, medicine.disease, Prognosis, Intensive care unit, Survival Analysis, Community-Acquired Infections, Infectious Diseases, Treatment Outcome, Immunoglobulin M, Immunology, biology.protein, Female, Antibody, business
Abstract

Little is known on the participation of immunoglobulin isotypes and subclasses in the pathogenesis of the severe disease caused by the pandemic influenza virus (influenza A(H1N1)pdm09).(1) To evaluate the association between plasma levels of IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE and outcome in patients with severe pandemic influenza. (2) To evaluate the association between immunoglobulin and cytokine levels in these patients.40 critically ill patients with community acquired pneumonia and influenza A(H1N1)pdm09 infection were recruited from November 2010 to February 2011. Plasma samples were collected during the first 24h following admission to the ICU. Immunoglobulins and 17 major cytokines were profiled in plasma.15 patients died (37.5%). When the association between clinical variables and prognosis was assessed, prior immunosuppression, APACHE II score, levels of IgG2 and levels of IgM were associated with outcome in a univariate Cox regression analysis. Kaplan Meier analysis showed that patients with levels of IgG2 and IgM59 and58 mg/dl respectively died earlier. Multivariate Cox regression analysis showed that APACHE II score and levels of IgM were the best predictors of outcome, being levels of IgM a protective factor against mortality. IgM was the immunoglobulin showing the largest number of negative correlations with cytokine levels.Our results support a central role of IgM in preventing uncontrolled inflammatory response and mortality in severe pandemic influenza. Early assessment of IgM could contribute to guide clinical decisions in these patients.

Published
2013

8. Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A

Author

José Albofedo-Sánchez, M. Blasco Navalpotro, Paloma Dorado Regil, S. Tormo, Luis Regalado, Eduardo Palencia, A. Tellería, Raul José González, J.M. Añón, Antonio Jareño, Jose Ramon Iruretagoyena Amiano, Elena Gallego, Angel Arenzana, Cecilia Hermosa, Laura Macaya, Luis Álvarez–Rocha, R. Granada, Antonio Albaya, Carlos Velayos, Dolores Ocaña Fernández, Ignacio Amestarán, Josep Ballus, Emilio Robles-Musso, José Mª Molina, Sonia Gómez-Rosado, Carlos Pey, Fernándo Bueno, Luis Miguel Prado López, Iñaki Catalán, Rosa María Díaz, Ana Trujillo, B. Santamaría, Virgilio Paricio, Antonia Socias, José Luis Ballesteros, Julio Canabal, J.C. Pozo, César Pérez–Calvo, Mónica Magret, B. Suberviola, P. Ugarte, Joaquim Ramón Cervelló, S Barbadillo, Loreto Vidaur, Pedro Ibañez, Bárbara Baladín, Pilar Luque, J Nolla, José Cuñat, Juan C. Figueira, Fernando Barcenilla, S. Garrido Ramírez de Arellano, Sisón, Fernando Arméstar, Arantxa Lander, M. Martín, Inés Navarrete, Antonio Cárdenas, M. Cruz Soriano, Miguel Angel Díaz Castellanos, Diego de Mendoza, Javier Pérez, Francisco del Río, Medhi Zaheri Beryanaki, Miguel González, I. Jimenez Urra, David Hernandez, Sandra Trefler, Lisardo Iglesias, Antonio Álvarez Terrero, JJ Díaz, Marta Ortíz, Francisco Álvarez-Lerma, A. Liétor, Concepción Vaquero, Susana Altaba, Isidro Prieto, M. Badia, Ángel Sánchez-Miralles, Almudena Simón, Nerea López de Arbina, Mª Jesús Huertos, Zoran Josic, M. I. Marquina Lacueva, Santiago Macias, J. Nava, C. Ferri, José A. Pastor, Rafael Sierra, Antoli Ribas, Quiroga, Ignacio Martin-Loeches, Eleuterio Merayo, Santiago Freita, Nieves Carrasco, L. Macaya Redin, Ana María Rojo López, F. Felices Abad, Patricia Albert, Leonardo Lorente, Rafael Caballero, Sergio Ruiz-Santana, Javier Martins, José M. Bonell, Eva Vilaboy, Juan B. López Messa, Xavier Balanzó, José Luna, Cristóbal León, Abilio Arrascaeta, M. C. Martín, Joaquim Páez, Ana Loza, Juliá-Narváez José, José Garnacho-Montero, Jordi Almirall, Zulema Ferreras, Elena Arnau, L. Cabre, Guillermo Sevilla, S. García, José Eugenio Guerrero, R. Guerrero, Enrique Marquez, José Luis Monzón, Yolanda Fernández, A. del Castillo, Thiago Lisboa, Teresa Recio, Asunción Marques, Ignacio Sánchez, Lluis Llopart, M. Rodriguez, José Pomares, Marcío Borges-Sa, José Blanquer, Juan Carlos Montejo, Mercedes Díaz, Carmen González, Rosa Mª Catalán, Fernández del Cabo, Rafael Mañez, Enrique Ferres, Bernardo Gil Rueda, Alejandro Algora, Jesús Blanco Varela, L. Canadell, Jordi Rello, Alberto Manzano, A. Andaluz Ojeda, Jaime Benitez Peyrat, Félix Goñi, Rafael Zaragoza, Miquel Ferrer, Eduard Mesalles, A. Alonso, Alberto Fernández-Zapata, Frutos Del Nogal Sáez, Alejandro Rodríguez, Águeda García-Rodríguez, Ignacio González, Antonio Pasilla, A. Vazquez, Zulema Paez, Assumpta Rovira, Alberto Sandiumenge, M. F. Esteban, Dolores Ocaña, Josu Insansti, José F. Prieto, Pedro Cobo, Manuel Alvarez, Luis Arnaiz, Javier Cebrian, Carlos Castillo Arenal, Ricard Jordà Marcos, Manuel Luis Avellanas, Emili Diaz, Santiago Alberto Picos, Juan Carlos Vergara, Montserrat Valverdú-Vidal, J. J. Cáceres, Enrique Maraví-Poma, Diego López, Juan Bonastre, Esteban Fernández, P. Galdós, Sofía Martínez, Bernabé Alvarez-Sánchez, Fabiola Tena Ezpeleta, Ana de Pablo, R. Ramos, Eva Maria Saborido, Roberto Reig Valero, Enrique Cerdá, S. Sánchez-Alonso, Mercedes Catalán, Victor Jose López-Ciudad, M. Ortiz Piquer, Mariano Martínez, Amparo Paredes, Belén Agrela Romero, Jordi Vallés, M. Palamo, Jos M. Latour, J. González de Molina, Francisco Gurri, Jose Mª Montón, Juan José Díaz, Ana Díaz Lamas, Álvaro García, Josep Mª Sirvent, Jose Ángel Berezo, Mª José García-Ramos, Sergio Manuel Butí, Federico Gordo, Lorenzo Socias, Manuel Rodríguez-Carvajal, Mª Lourdes Cordero, Mercedes Palomar, Fernando García-López, Cecilia Carbayo, Pilar Martínez, R. Hinojosa, Dolores Vila, Francisco Lobato, Francisco Fernández, Juan Cortez, Pedro Olaechea, M. Ángel García, Mª Jesús López Pueyo, Antoni Torres, Beatriz Galván, Mª Carmen García-Torrejón, J. A. Cambronero, Bárbara Balandin Moreno, A. Canabal, Sergio F. Martínez, Nagore González, A. Belenger, Francisco Mariscal, P. Marco, Luis Marina, Francisco García, Mª Luisa Gómez Grande, S. Sánchez-Morcillo, Javier Fierro, and C. Guía

Subjects
Microbiology (medical), Adult, Male, medicine.medical_specialty, Oseltamivir, Time Factors, medicine.drug_class, medicine.medical_treatment, Critical Illness, Antiviral Agents, law.invention, chemistry.chemical_compound, Influenza A Virus, H1N1 Subtype, law, Internal medicine, Influenza, Human, medicine, Humans, Pharmacology (medical), Prospective Studies, Prospective cohort study, Pharmacology, Mechanical ventilation, Neuraminidase inhibitor, business.industry, Middle Aged, medicine.disease, Intensive care unit, Surgery, Pneumonia, Infectious Diseases, Treatment Outcome, chemistry, Propensity score matching, Cohort, Female, business
Abstract

Received 8 October 2010; returned 9 November 2010; revised 2 December 2010; accepted 6 December 2010Objectives: The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A(2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between thetiming of antiviral administration and intensive care unit (ICU) outcomes.Methods: Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection.Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) withoseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint.Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality.Results: Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients requiredmechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy andwere included in the study group. All patients received oseltamivir for a median duration of 10 days (interquar-tile range 8–14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groupswere comparable in terms of main clinical variables. ICU length of stay (22.7+16.7 versus 18.4+14.2 days;P¼0.03), hospital length of stay (34.0+20.3 versus 27.2+18.2 days; P¼0.001) and MV days (17.4+15.2versus 14.0+12.4; P¼0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than inET (21.5%; OR¼1.9; 95% CI 1.06–3.41). A multivariate model identified ET (OR¼0.44; 95% CI 0.21–0.87) asan independent variable associated with reduced ICU mortality. These results were confirmed by propensityscore analysis (OR¼0.44; 95% CI 0.22–0.90; P,0.001).Conclusions: Our findings suggest that early oseltamivir administration was associated with favourableoutcomes among critically ill ventilated patients with 2009 H1N1 virus infection.Keywords: antiviral treatment, prognosis, pneumonia

Published
2011

9. IgA level in plasma as a differential factor for influenza infection in severe viral pneumonia

Author

Mar Justel, Paula Ramirez, Jesus F. Bermejo-Martin, Angel Estella, Raúl Ortiz de Lejarazu, Lorenzo Socias, Raquel Almansa, Catia Cilloniz, Antoni Torres, Jesús Blanco, Sara Rosich, Ignacio Martin-Loeches, David Andaluz-Ojeda, Jose Ángel Berezo, and Ana Loza

Subjects
Adult, Male, Immunoglobulin A, Pneumonia, Viral, Article, Diagnosis, Differential, Plasma, Virology, Influenza, Human, medicine, Humans, Aged, Aged, 80 and over, biology, business.industry, Middle Aged, medicine.disease, Infectious Diseases, Viral pneumonia, Immunology, biology.protein, Female, Differential diagnosis, business, Differential (mathematics)
Published
2014
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