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1. Differences in clinical outcomes of bloodstream infections caused by Klebsiella aerogenes, Klebsiella pneumoniae and Enterobacter cloacae: a multicentre cohort study

Author

Mariana Guedes, David Gathara, Inmaculada López-Hernández, Pedro María Martínez Pérez-Crespo, María Teresa Pérez-Rodríguez, Adrian Sousa, Antonio Plata, Jose María Reguera-Iglesias, Lucía Boix-Palop, Beatriz Dietl, Juan Sevilla Blanco, Carlos Armiñanzas Castillo, Fátima Galán-Sánchez, Clara Natera Kindelán, Alfredo Jover-Saenz, Josune Goikoetxea Aguirre, Ana Alemán Alemán, Teresa Marrodán Ciordia, Alfonso del Arco Jiménez, Jonathan Fernandez-Suarez, Luis Eduardo Lopez-Cortes, Jesús Rodríguez-Baño, and PROBAC/GEIRAS-SEIMC/SAMICEI group

Subjects
Bloodstream infection, Klebsiella aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Mortality, Recurrence, Therapeutics. Pharmacology, RM1-950, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Abstract Background Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. Methods Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. Results Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. Conclusions Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.

Published
2024
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2. Host genetic variants associated with susceptibility and severity of pneumococcal pneumonia in adult patients

Author

Lucía Boix-Palop, María J. Arranz, Anna Sangil, Beatriz Dietl, Mariona Xercavins, Josefa Pérez, and Esther Calbo

Subjects
Genetic variants, Polymorphisms, Pneumococcal community-acquired pneumonia, Host susceptibility, Severity and outcome, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Pneumococcal community-acquired pneumonia (P-CAP) is a major cause of morbidity and hospitalization. Several host genetics factors influencing risk of pneumococcal disease have been identified, with less information about its association with P-CAP. The aim of the study was to assess the influence of single nucleotide polymorphisms (SNP) within key genes involved in the innate immune response on the susceptibility to P-CAP and to study whether these polymorphic variants were associated with the severity and outcome of the episodes in a cohort of adult Caucasian patients. Methods Seventeen SNPs from 7 genes (IL-R1, IL-4, IL-10, IL-12B, NFKBIA, NFKBIE, NFKBIZ) were analyzed. For susceptibility, a case-control study including a cohort of 57 adult with P-CAP, and 280 ethnically matched controls was performed. Genetic influence on clinical severity and outcome was evaluated in a prospective observational study including all consecutive adult P-CAP patients from November 2015 to May 2017. Results The NFKBIA polymorphism rs696 and a haplotype combination were associated with susceptibility to P-CAP (OR = 0.62, p = 0.005 and OR = 0.63, p = 0.008, respectively). The SNP IL4 rs2227284 was associated with severe P-CAP (OR = 2.17, p = 0.04). IL-R1 (rs3917267) and IL-10 (rs3024509) variants were related with respiratory failure (OR = 3.31, p = 0.001 and OR = 0.18, p = 0.003, respectively) as well as several haplotype combinations in NFKBIA, NFKBIZ, IL-R1 and IL-10 (p = 0,02, p = 0,01, p = 0,001, p = 0,03, respectively). CURB-65 values were associated with the IL-10 rs3024509 variant (beta = − 0.4, p = 0.04), and with haplotype combinations of NFKBIZ and IL-10 (p = 0.05, p = 0.04, respectively). Genetic variants in IL-10 (rs3024509) and in IL-12B (rs730691) were associated with PSI values (beta = − 0.54, p = 0.01, and beta = − 0.28, p = 0.04, respectively), as were allelic combinations in IL-R1 (p = 0.02) and IL-10 (p = 0.01). Finally, several polymorphisms in the IL-R1 gene (rs13020778, rs2160227, & rs3917267) were associated with the time elapsed until clinical stability (beta = − 0.83, p = 0.03; beta = − 1, p = 0.02 and beta = 1.07, p = 0.008, respectively). Conclusions A genetic variant in NFKBIA was associated with susceptibility to P-CAP in adult Caucasian patients and genetic variants from key cytokines of the innate immune response (Il-4, IL-10, IL-R1 and IL-12B) and NF-κB inhibitors were associated with different phenotypes of severe P-CAP. If validated, these SNPs may help to identify people at risk of P-CAP or severe P-CAP on which preventive measures could be applied.

Published
2023
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3. Risk factors associated with inappropriate empirical antimicrobial treatment in bloodstream infections. A cohort study

Author

Beatriz Dietl, Lucía Boix-Palop, Laura Gisbert, Aina Mateu, Gemma Garreta, Mariona Xercavins, Cristina Badía, María López-Sánchez, Josefa Pérez, and Esther Calbo

Subjects
bacteremia, bloodstream infections (BSI), anti-bacterial agents-therapeutic use, risk factors, antimicrobial therapy, antimicrobial stewardship (ASP) intervention, Therapeutics. Pharmacology, RM1-950
Abstract

Introduction: Bloodstream infections (BSI) are a major cause of mortality all over the world. Inappropriate empirical antimicrobial treatment (i-EAT) impact on mortality has been largely reported. However, information on related factors for the election of i-EAT in the treatment of BSI in adults is lacking. The aim of the study was the identification of risk-factors associated with the use of i-EAT in BSI.Methods: A retrospective, observational cohort study, from a prospective database was conducted in a 400-bed acute-care teaching hospital including all BSI episodes in adult patients between January and December 2018. The main outcome variable was EAT appropriation. Multivariate analysis using logistic regression was performed.Results: 599 BSI episodes were included, 146 (24%) received i-EAT. Male gender, nosocomial and healthcare-associated acquisition of infection, a high Charlson Comorbidity Index (CCI) score and the isolation of multidrug resistant (MDR) microorganisms were more frequent in the i-EAT group. Adequation to local guidelines’ recommendations on EAT resulted in 91% of appropriate empirical antimicrobial treatment (a-EAT). Patients receiving i-EAT presented higher mortality rates at day 14 and 30 when compared to patients with a-EAT (14% vs. 6%, p = 0.002 and 22% vs. 9%, p < 0.001 respectively). In the multivariate analysis, a CCI score ≥3 (OR 1.90 (95% CI 1.16–3.12) p = 0.01) and the isolation of a multidrug resistant (MDR) microorganism (OR 3.79 (95% CI 2.28–6.30), p < 0.001) were found as independent risk factors for i-EAT. In contrast, female gender (OR 0.59 (95% CI 0.35–0.98), p = 0.04), a correct identification of clinical syndrome prior to antibiotics administration (OR 0.26 (95% CI 0.16–0.44), p < 0.001) and adherence to local guidelines (OR 0.22 (95% CI 0.13–0.38), p < 0.001) were identified as protective factors against i-EAT.Conclusion: One quarter of BSI episodes received i-EAT. Some of the i-EAT related factors were unmodifiable (male gender, CCI score ≥3 and isolation of a MDR microorganism) but others (incorrect identification of clinical syndrome before starting EAT or the use of local guidelines for EAT) could be addressed to optimize the use of antimicrobials.

Published
2023
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4. Related Factors to Streptococcus pneumoniae Invasive Infection and Clinical Manifestations: The Potential Role of Nasopharyngeal Microbiome

Author

Beatriz Dietl, Desirée Henares, Lucía Boix-Palop, Carmen Muñoz-Almagro, Javier Garau, and Esther Calbo

Subjects
microbiota, nasopharynx, Streptococcus pneumoniae, pneumococcal infections, invasive pneumococcal disease, Medicine (General), R5-920
Abstract

Infections of the lower respiratory tract, such as pneumonia, are one of the leading causes of death worldwide. Streptococcus pneumoniae might colonize the upper respiratory tract and is the main aetiological agent of community-acquired pneumonia (CAP). In the last decades, several factors related to the host, the microorganism and the antibiotic therapy have been investigated to identify risk factors associated with the development of invasive pneumococcal disease (IPD). Nevertheless, these factors themselves do not explain the risk of developing disease or its severity. Recently, some studies have focused on the importance of nasopharyngeal (NP) microbiome and its relation to respiratory health. This review presents existing evidence of the potential role of NP microbiome in the development of IPD.

Published
2021
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5. Epigenome-wide association study of COVID-19 severity with respiratory failure

Author

Manuel Castro de Moura, Veronica Davalos, Laura Planas-Serra, Damiana Alvarez-Errico, Carles Arribas, Montserrat Ruiz, Sergio Aguilera-Albesa, Jesús Troya, Juan Valencia-Ramos, Valentina Vélez-Santamaria, Agustí Rodríguez-Palmero, Judit Villar-Garcia, Juan P. Horcajada, Sergiu Albu, Carlos Casasnovas, Anna Rull, Laia Reverte, Beatriz Dietl, David Dalmau, Maria J. Arranz, Laia Llucià-Carol, Anna M. Planas, Jordi Pérez-Tur, Israel Fernandez-Cadenas, Paula Villares, Jair Tenorio, Roger Colobran, Andrea Martin-Nalda, Pere Soler-Palacin, Francesc Vidal, Aurora Pujol, and Manel Esteller

Subjects
Coronavirus, SARS-CoV-2, COVID-19, Epigenetics, DNA methylation, Medicine, Medicine (General), R5-920
Abstract

Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. Methods: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. Findings: The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. Interpretation: We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2. Funding: The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.

Published
2021
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7. Short versus long course therapy in the treatment of febrile urinary tract infections in men based on serum PSA values

Author

Helena Monzón, Laura Gisbert, Meritxell Salvadó, Miquel Puyol, Mariona Xercavins, Asunción Gasós, Maria Sanjaume, Beatriz Dietl, Josep Maria Caballero, Patricia Sigüenza, Ángeles Jaen, Javier Garau, and Esther Calbo

Subjects
Male, Adult, Aged, 80 and over, Young Adult, Urinary Tract Infections, Internal Medicine, Humans, Prospective Studies, Middle Aged, Prostate-Specific Antigen, Escherichia coli Infections, Aged, Anti-Bacterial Agents
Abstract

Febrile urinary tract infections (fUTI) in men are frequently complicated with subclinical prostatic involvement, measured by a transient increase in serum prostate-specific-antigen (sPSA). The aim of this study was to evaluate recurrence rates in a 6-month follow-up period of 2-week versus 4-week antibiotic treatment in men with fUTI, based on prostatic involvement. Clinical and microbiological cure rates at the end-of-therapy (EoT) were also assessed.Open label, not-controlled, prospective study. Consecutive men diagnosed of fUTI were included. Duration of therapy was 2 weeks for patients with a sPSA level5mg/L (short duration therapy, SDT) or 4 weeks for PSA5 mg/L (long duration therapy, LDT).Ninety-one patients were included; 19 (20%) received SDT. Median age was 56.9 years (range 23-88). Bacteremia was present in 9.8% of patients (Escherichia coli was isolated in 91%). Both groups had similar demographic, clinical characteristics and laboratory findings. Median PSA levels were 2.3 mg/L in the SDT group vs 23.4 mg/L in the LDT group. In the 6-month visit, 26% of patients had achieved complete follow-up. Nonsignificant differences between groups were found neither in recurrence rates after 6 months (9% in SDT vs 10% in LDT) nor in clinical or microbiological cure rates at EoT (100% in SDT vs 95% in LDT and 95% in SDT vs 93% in LDT respectively).One fifth of men with fUTI did not present apparent prostatic involvement. A 2-week regimen seems adequate in terms of clinical, microbiological cure and recurrence rates for those patients without PSA elevation.

Published
2022
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8. Risk of cardiac device-related infection in patients with late-onset bloodstream infection. Analysis on a National Cohort

Author

Lucía Boix-Palop, Beatriz Dietl, Esther Calbo, Andrea Di Marco, Mariona Xercavins, Pedro María Martínez Pérez-Crespo, Adrián Sousa, Miguel Montejo Baranda, Jesús Rodríguez-Baño, Luis Eduardo López-Cortés, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, and European Commission

Subjects
Adult, Cohort Studies, Microbiology (medical), Staphylococcus aureus, Infectious Diseases, Risk Factors, Humans, Bacteremia, Prospective Studies, Communicable Diseases, Enterococcus, Defibrillators, Implantable
Abstract

[Objectives] To determine the incidence of cardiac device-related infection (CDRI) among patients with cardiac device (CD) during late-onset bloodstream infection (BSI) and to identify the risk factors associated with CDRI., [Methods] Patients with a CD (cardiac implantable electronic devices -CIED- and/or prosthetic heart valve -PHV-) and late-onset-BSI (>1 year after the CD implantation/last manipulation) were selected from the PROBAC project, a prospective, observational cohort study including adult patients with bacteraemia consecutively admitted to 26 Spanish hospitals from October 2016 to March 2017. Multivariate analyses using logistic regression were performed to identify the risk factors associated with CDRI., [Results] 317 BSI from patients carrying a CD were registered, 187 (56.2%) were late-onset-BSI. A total of 40 (21.4%) CDRI were identified during late-onset-BSI. The CDRI cumulative incidence in Gram-positive-BSI was 41.8% (38/91), with S. aureus, Enterococcus spp. and viridans streptococci showing the greatest percentages: 40% (12/30), 42% (11/26) and 75% (6/8), respectively. Independent predictors of CDRI were an unknown source of infection (OR: 2.88 [CI 95%:1.18–7.06], p = 0.02), Gram-positive-aetiology (23.1 [5.23–102.1], p < 0.001) and persistent bacteraemia (4.81 [1.21–19], p = 0.03). In an exploratory analysis, S. aureus (3.99 [1.37–11.65], p = 0.011), Enterococcus spp. (5.21 [1.76–15.4], p = 0.003) and viridans streptococci (28.7 [4.71–173.5], p < 0.001) aetiology were also found to be risk factors for CDRI., [Conclusions] CDRI during late-onset-BSI is a frequent phenomenon. Risk of CDRI differs among species, happening in almost half of the Gram-positive-BSI. An unknown source of the primary infection, Gram-positive-aetiology -especially S. aureus, Enterococcus spp. and viridans streptococci-, and persistent bacteraemia were identified as risk factors for CDRI., This study was funded by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, through the following grants: Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001; RD16/0016/0007; RD16/0016/0008; RD16/0016/0012), co-financed by European Development Regional Fund ‘A way to achieve Europe’, Operative Program Intelligent Growth 2014–2020, and PI16/01432.

Published
2022
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9. Update on the role of ceftazidime-avibactam in the management of carbapenemase-producing Enterobacterales

Author

Laura Martinez, Esther Calbo, Javier Garau, and Beatriz Dietl

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, Avibactam, 030106 microbiology, Cephalosporin, Salvage therapy, Carbapenem-resistant enterobacteriaceae, Ceftazidime, Microbiology, beta-Lactamases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Bacterial Proteins, Enterobacteriaceae, Drug Resistance, Multiple, Bacterial, Enterobacterales, medicine, Animals, Humans, 030212 general & internal medicine, Intensive care medicine, business.industry, Enterobacteriaceae Infections, medicine.disease, Ceftazidime/avibactam, Anti-Bacterial Agents, Multiple drug resistance, Drug Combinations, Pneumonia, chemistry, business, Azabicyclo Compounds, medicine.drug
Abstract

Ceftazidime-avibactam is a novel combination of a known cephalosporin and a non-β-lactam/β-lactamase inhibitor that has been approved for the treatment of complicated intra-abdominal and urinary tract infections, hospital-acquired pneumonia as well as Gram-negative infections with limited treatment options in Europe. Since its approval, it has been used in patients with infections due to carbapenem-resistant bacteria, in many occasions as off-label indication or salvage therapy, with promising clinical and microbiological cure rates. Emergence of resistance during therapy to this new combination has already been described, which is a matter of concern. A rational use of these new therapeutic options is critical in the multidrug resistance era. The current review focuses on the clinical experience in real life of ceftazidime-avibactam use in the treatment of carbapenemase-producing Enterobacterales.

Published
2020
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10. Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Author

Jesús Rodríguez-Baño, Jerónimo Pachón, Jordi Carratalà, Pablo Ryan, Inmaculada Jarrín, María Yllescas, José Ramón Arribas, Juan Berenguer, Esther Aznar Muñoz, Pedro Gil Divasson, Patricia González Muñiz, Clara Muñoz Aguirre, Marta Díaz Menéndez, Fernando de la Calle Prieto, Marta Arsuaga Vicente, Elena Trigo Esteban, Ignacio Pérez Valero, Rosa de Miguel Buckley, Julen Cadiñaños Loidi, Beatriz Diaz Pollan, Luz Martín Carbonero, Juan Carlos Ramos Ramos, Belén Loeches Yagüe, Rocío Montejano Sánchez, Juan González García, Julio García Rodríguez, Margarita Ramírez, Isabel Gutiérrez, Francisco Tejerina, Teresa Aldámiz-Echevarría, Cristina Díez, Chiara Fanciulli, Leire Pérez-Latorre, Blanca Pinilla, Juan Carlos López, Ana Such Diaz, Elena Álvaro Alonso, Juan Torres Macho, Guillermo Cuevas Tascon, Eva Jiménez González de Buitrago, Fátima Brañas Baztán, Jorge Valencia de la Rosa, Mario Pérez Butragueño, Inés Fernández Jiménez, Gemma Muñiz Nicolás, Antonia Sepúlveda Berrocal, Alberto Gato Díez, María Pilar Toledano Sierra, María Paz García Butenegro, Ana Isabel Peláez Ballesta, Elena Morcillo Rodríguez, Isidoro Fernández Romero, Cristina Peláez Ballesta, María Isabel Guirado Torrecillas, Josune Goikoetxea Agirre, Elena Bereciartua Bastarrica, Laura Guio Carrión, Regino Rodríguez Álvarez, Marta Ibarrola Hierro, Isabel A. Pérez Hernández, Inés Pérez Zapata, Sergio Román Soto, Mohamed Kallouchi, Juan Ramón Domínguez Vicent, Rafae Silvariño Fernández, Jon Ugalde Espiñeira, Ainhoa Sanjuan López, Silvia García Martínez, Mikel Temprano Gogenola, Víctor Asensi, Silvia Suárez, Lucia Suárez, Carmen Yllera, María Rivas-Carmenado, Alberto Romero-Palacios, Jesús Ruiz Aragón, Patricia Jiménez Aguilar, Ma Luisa Fernández Ávila, Rosario Castilla Ortiz, Vanesa Alende Castro, Cristina Pérez García, Marta Fernández Morales, María Lorena María Valle Feijoo Begoña Rodríguez Ferreira, Joan Gómez-Junyent, Judit Villar-García, Inmaculada López-Montesinos, Itziar Arrieta-Aldea, Abora Rial-Villavecchia, Elisa García Vázquez, Aychel Elena Roura Piloto, Encarnación Moral Escudero, Alicia Hernández Torres, Helena Albendín Iglesias, David Vinuesa García, Clara Martínez Montes, Francisco Javier De la Hera Fernández, Francisco Anguita Santos, Andrés Ruiz Sancho, Vicens Díaz de Brito Fernández, Montserrat Sanmarti Vilamala, Sergio España Cueto, Daniel Molina Morant, Araceli González-Cuevas, Joel Elías Chara Cervantes, Guillem Policarpo Torres, Meritxell Ortega Montoliu, Mònica Angerri Nadal, Ariadna De Genover Gil, Eleni Patera, Rita Godoy Lorenzo, Evangelia Anna María Zioga, Virginia Isern Fernández, Carlos Enrique Sabbagh Fajardo, Ana Ferrer Ribera, Carlos Bea Serrano, Rosa Oltra Sempere, Sara Vela Bernal, Paloma Albiol Viñals, Miguel Pedromingo Kus, María Ángeles Garcinuño, Silvana Fiorante, Sergio Pérez Pinto, Alexandra de la Vega, María Carmen Fariñas Álvarez, Claudia González Rico, Francisco Arnaiz de las Revillas, Teresa Giménez, Jorge Calvo, Yolanda Meije Castillo, Alejandra Duarte Borges, Júlia Pareja Coca, Mercedes Clemente Presas, Xavier Sanz Salvador, Ma Teresa Pérez Rodríguez, Adrián Sousa, Alexandre Pérez González, Rebeca Longueira, Alejandro Araujo, Blanca Alonso Martínez, Laura García Escudero, Sara Lidia Kamel Rey, David Roa Alonso, Juan Pablo Avilés Parra, Iván Pelegrín Senent, Rosana Rouco Esteves Marques, Laia Raich Montiu, Jessica Souto Higueras, Manuel Alejandro Gálvez Bobadilla, Jorge Parra Ruiz, Violeta Ramos Sesma, Sara Velasco Fuentes, Laura García Pereña, Alfonso Lluna Carrascosa, Sergio Gilaberte Reyzábal, Mónica Liébana Gómez, Juan Salillas Hernando, Alberto Serrano Martínez, Miguel Torralba González de Suso, Patricia Martínez Martín, Isabel Rábago Lorite, Patricia González-Ruano Pérez, Beatriz Pérez-Monte Mínguez, Ángeles García Flores, Pere Comas Casanova, Andrea Martín Plata, Sergio Manuel Santana Báez, Oscar Sanz Peláez, Karim Mohamed Ramírez, José María Robaina Bordón, Helem Haydeé Vílchez Rueda, Melchor Riera Jaume, Gemma Mut Ramon, Meritxell Gavalda Manso, Lluis Planas Bibiloni, Laura Castelo Corral, Lucía Ramos Merino, Efrén Sánchez Vidal, María Rodríguez Mayo, Enrique Míguez Rey, José M. García de Lomas Guerrero, Javier De la Torre Lima, Ana Correa Ruiz, Fernando Fernández Sánchez, Nicolás Jiménez-García, José Luis Sierra-Monzón, Borja Gracia-Tello, María Hernández-Bonaga, Galadriel Pellejero, Marta Asín-Corrochano, Lucia Boix Palop, Esther Calbo, Cristina Badía, Beatriz Dietl, Gómez Lucía, Ángel Domínguez-Castellano, María José Ríos-Villegas, María D. del Toro, Zaira R. Palacios Baena, Elena Salamanca-Rivera, Elena Marín, Virginia Almadana, Salvador Pérez-Galera, Luisa González-Iglesias, Gabriela Abelenda-Alonso, Claudia Álvarez-Pouso, Francesc Escrihuela, Carlota Gudiol, Laia Lorenzo-Esteller, Jordi Niubó, Daniel Podzamczer, Miquel Pujol, Alexander Rombauts, Miguel Salvert Lletí, Ricardo Gil Sánchez, Marta Jiménez Escrig, Laura Parra Gómez, Mariona Tasias Pitarch, Marta Navarro Vilasaró, María Luisa Machado Sicilia, Aina Gomila Grange, Sonia Calzado Isbert, Nerea Carrasco Antón, Elizabet Petkova-Saiz, Alfonso Cabello Úbeda, Miguel Górgolas Hernández-Mora, Olga Sánchez-Pernaute, Carlos Dueñas Gutiérrez, Javier Martin Guerra, José Javier Castrodeza Sanz, Virginia Fernández Espinilla, Laura Rodríguez Fernández, Juan González-Moreno, Aroa Villoslada Gelabert, María Antonia Ribot Sanso, María Victoria Fernández-Baca, Almudena Hernández Milian, Miguel Ángel Morán Rodríguez, Zuriñe Ortiz de Zárate Ibarra, José Joaquin Portu Zapirain, Ester Saez de Adana Arroniz, Juan Carlos Gainzarain Arana, Olga Meca Birlanga, Ma Jesús del Amor Espín, Montserrat Viqueira González, Josefina García García, Onofre Martínez Madrid, Enrique Bernal Morell, Antonia Alcaraz, Ángeles Muñoz, Ignacio Pina, Vicente de la Rosa, Tamara Caínzos Romero, Sabela Sánchez Trigo, Ana Isabel Mariño Callejo, Hortensia Álvarez Díaz, Nieves Valcarce Pardeiro, Adriana Sánchez Serrano, Diana Piñar Cabezos, Eva Pilar García Villalba, Carmen Aguayo Jiménez, María Ruíz Campuzano, Virginia Naranjo Velasco, Marta Santos Peña, Juan Mora Delgado, Israel Sevilla Moreno, Cristina Lojo Cruz, Xabier Kortajarena Urkola, José Antonio Iribarren Loyarte, María Jesús Bustinduy Odriozola, Maialen Ibarguren Pinilla, Ignacio Álvarez Rodríguez, Francisco Javier Martínez Marcos, Francisco Javier Rodríguez Gómez, Isabel Asschert Agüero, Francisco Muñoz Beamud, Antonio José Ruiz Reina, Jara Llenas-García, Inmaculada González-Cuello, Elena Hellín-Valiente, Esther Martínez Birlanga, José Manuel Tafalla Torres, Jorge Calderón Parra, Gabriela Escudero López, Isabel Gutiérrez Martín, Ane Andrés Eisenhofer, Sonia García Prieto, Raquel Álvarez Franco, Daniel Roger Zapata, Blanca Martínez Cifre, Elena Aranda Rife, Irene Martín Rubio, André Barbosa Ventura, Javier Garrido, Concepción Gonzalo, Iván Piñero, Nieves de la Cruz Felipe, Eva Talavera García, Marta Lamata Subero, Paula Mendoza Roy, María Soledad García de Carlos, Justo Lajusticia Aisa, Lorea Arteche Eguizabal, Ainhoa Urrutia Losada, Saioa Domingo Echaburu, Pedro Ángel Cuadros Tito, Gurutz Orbe Narváez, Ma del Carmen Liébana Martos, Carolina Roldán Fontana, Carmen Herrero Rodríguez, Gaspar Duro Ruiz, Santiago Pérez Parra, Arantzazu Mera Fidalgo, Miquel Hortos Alsina, Ana Alberich Conesa, Lourdes Bladé Vidal, Nicolás Merchante Gutiérrez, Eva León Jiménez, Reinaldo Espíndola Gómez, María Erostarbe Gallardo, Pedro Martínez Pérez-Crespo, José Miguel Cisneros, Manuela Aguilar-Guisado, Teresa Aldabó, Claudio Bueno, Elisa Cordero-Matía, Ana Escoresca, Carmen Infante, Martín Guillermo, Sonsoles Salto, Francesca Gioia, Pilar Vizcarra, Jesús Fortún Abete, Pilar Martín Dávila, Santiago Moreno Guillén, José A. Oteo Revuelta, Concepción García-García, Paula Santibañez Sáenz, Cristina Cervera Acedo, José M. Azcona Gutiérrez, José María Reguera Iglesias, Antonio Plata Ciezar, Lucia Valiente de Santis, Beatriz Sobrino Diaz, Juan Diego Ruiz Mesa, Ministerio de Ciencia e Innovación, Fundación SEIMC/GeSIDA, Instituto de Salud Carlos III - ISCIII, European Regional Development Fund (ERDF/FEDER), Red Española de Investigación en SIDA, Red Española de Investigación en Patología Infecciosa, UAM. Departamento de Medicina, UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología, Universidad de Cantabria, SAM-COVID Study Group, [Rodríguez-Baño,J] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Rodríguez-Baño,J, Pachón,J] Departamento de Medicina, Universidad de Sevilla, Spain. [Rodríguez-Baño,J, Pachón,J] Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain. [Pachón,J] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Carratalà,J] Servei de Malalties Infeccioses, Hospital Universitari de Bellvitge, Barcelona, Spain. [Carratalà,J] Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain. [Carratalà,J] Universitat de Barcelona, Barcelona, Spain. [Ryan,P] Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain. [Jarrín,I] Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain. [Yllescas,M] Fundación SEIMC/GeSIDA, Madrid, Spain. [Arribas,JR] Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. [Arribas,JR] Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain. [Berenguer,J] Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Berenguer,J] Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain., Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Red de Investigación Cooperativa en Investigación en Sida (España), Red de Investigación Cooperativa en Investigación en Patología Infecciosa (España), Gilead Sciences, ViiV Healthcare, AbbVie Pharmaceuticals, Merck & Co, Janssen Biotech, Teva Pharmaceutical Industries, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Universidad de Sevilla. Departamento de Medicina, Instituto Carlos III (España), and Unión Europea

Subjects
0301 basic medicine, Male, law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Organisms::Viruses::RNA Viruses::Nidovirales::Coronaviridae [Medical Subject Headings], Randomized controlled trial, law, Adrenal Cortex Hormones, Clinical endpoint, Medicine, 030212 general & internal medicine, Hospital Mortality, Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Vital Statistics::Mortality [Medical Subject Headings], Adrenocortical hormones, Hazard ratio, General Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Intubation::Intubation, Intratracheal [Medical Subject Headings], Middle Aged, Tocilizumab, Hospitalization, Infectious Diseases, Treatment Outcome, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections [Medical Subject Headings], Drug Therapy, Combination, Female, Cohort study, Microbiology (medical), medicine.medical_specialty, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections::Severe Acute Respiratory Syndrome [Medical Subject Headings], Combination therapy, Medicina, Hyperinflammatory state, 030106 microbiology, Estudios de cohortes, Antibodies, Monoclonal, Humanized, Article, 03 medical and health sciences, Internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], Intubation, Intratracheal, Mortalitat, Humans, Corticosteroids, Mortality, Corticoesteroides, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Aged, Proportional Hazards Models, Retrospective Studies, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Inflammation, business.industry, SARS-CoV-2, COVID-19, Odds ratio, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Adrenal Cortex Hormones [Medical Subject Headings], Corticosteroides, COVID-19 Drug Treatment, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Propensity Score [Medical Subject Headings], chemistry, Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Propensity score matching, Mortalidad, Monoclonal antibodies, business, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Anticossos monoclonals
Abstract

© 2020 The Author(s)., [Objectives]: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., [Methods]: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., [Results]: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001)., [Conclusions]: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

Published
2021

11. 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

12. Epigenome-wide association study of COVID-19 severity with respiratory failure

Author

Maria J. Arranz, David Dalmau, Sergiu Albu, Jesús Troya, Aurora Pujol, Valentina Vélez-Santamaría, Roger Colobran, Francesc Vidal, Anna M. Planas, Jair Tenorio, Laia Llucià-Carol, Carles Arribas, Juan Valencia-Ramos, Sergio Aguilera-Albesa, Damiana Álvarez-Errico, Agustí Rodríguez-Palmero, Andrea Martín-Nalda, Jordi Pérez-Tur, Israel Fernandez-Cadenas, Paula Villares, Manuel Castro de Moura, Carlos Casasnovas, Pere Soler-Palacín, Anna Rull, Juan Pablo Horcajada, Laia Reverté, Beatriz Dietl, Judit Villar-García, Manel Esteller, Montserrat Ruiz, Veronica Davalos, Laura Planas-Serra, Josep Carreras Leukemia Foundation, Fundació Privada Cellex, Generalitat de Catalunya, Institut Català de la Salut, [Castro de Moura M, Davalos V, Alvarez-Errico D, Arribas C] Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Catalonia, Spain. [Planas-Serra L, Ruiz M] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Colobran R] Servei d’Immunologia, Servei de Genètica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Martin-Nalda A, Soler-Palacin P] Unitat de Patologia Infecciosa i Immunodeficiències de Pediatria, Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, enfermedades respiratorias::trastornos respiratorios::insuficiencia respiratoria [ENFERMEDADES], Male, Medicine (General), Genome-wide association study, Disease, medicine.disease_cause, COVID-19 (Malaltia), Severity of Illness Index, Cohort Studies, Epigenome, 0302 clinical medicine, Insuficiència respiratòria - Aspectes genètics, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Medicine, Coronavirus, DNA methylation, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], General Medicine, Methylation, Middle Aged, Respiratory Tract Diseases::Respiration Disorders::Respiratory Insufficiency [DISEASES], CpG site, 030220 oncology & carcinogenesis, Female, Epigenetics, Respiratory Insufficiency, Respiratory insufficiency, Research Paper, Adult, Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Other subheadings::Other subheadings::Other subheadings::/virology [Other subheadings], General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Young Adult, R5-920, Humans, Otros calificadores::Otros calificadores::Otros calificadores::/virología [Otros calificadores], business.industry, SARS-CoV-2, Reproducibility of Results, COVID-19, Epigenètica, Genòmica, 030104 developmental biology, Insuficiència respiratòria, Spain, Immunology, técnicas de investigación::métodos epidemiológicos::diseño de la investigación epidemiológica::estudio de asociación genómica completa [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], CpG Islands, Interferons, business, Genome-Wide Association Study
Abstract

Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. Methods: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. Findings: The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. Interpretation: We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2., The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.

Published
2021

13. SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Author

Matteo D’Antonio, Jennifer P. Nguyen, Timothy D. Arthur, Hiroko Matsui, Agnieszka D’Antonio-Chronowska, Kelly A. Frazer, Benjamin M. Neale, Mark Daly, Andrea Ganna, Christine Stevens, Gita A. Pathak, Shea J. Andrews, Masahiro Kanai, Mattia Cordioli, Juha Karjalainen, Renato Polimanti, Matti Pirinen, Nadia Harerimana, Kumar Veerapen, Brooke Wolford, Huy Nguyen, Matthew Solomonson, Rachel G. Liao, Karolina Chwialkowska, Amy Trankiem, Mary K. Balaconis, Caroline Hayward, Anne Richmond, Archie Campbell, Marcela Morris, Chloe Fawns-Ritchie, Joseph T. Glessner, Douglas M. Shaw, Xiao Chang, Hannah Polikowski, Petty E. Lauren, Hung-Hsin Chen, Zhu Wanying, Hakon Hakonarson, David J. Porteous, Jennifer Below, Kari North, Joseph B. McCormick, Paul R.H.J. Timmers, James F. Wilson, Albert Tenesa, Kenton D’Mellow, Shona M. Kerr, Mari E.K. Niemi, Lindokuhle Nkambul, Kathrin Aprile von Hohenstaufen, Ali Sobh, Madonna M. Eltoukhy, Amr M. Yassen, Mohamed A.F. Hegazy, Kamal Okasha, Mohammed A. Eid, Hanteera S. Moahmed, Doaa Shahin, Yasser M. El-Sherbiny, Tamer A. Elhadidy, Mohamed S. Abd Elghafar, Jehan J. El-Jawhari, Attia A.S. Mohamed, Marwa H. Elnagdy, Amr Samir, Mahmoud Abdel-Aziz, Walid T. Khafaga, Walaa M. El-Lawaty, Mohamed S. Torky, Mohamed R. El-shanshory, Chiara Batini, Paul H. Lee, Nick Shrine, Alexander T. Williams, Martin D. Tobin, Anna L. Guyatt, Catherine John, Richard J. Packer, Altaf Ali, Robert C. Free, Xueyang Wang, Louise V. Wain, Edward J. Hollox, Laura D. Venn, Catherine E. Bee, Emma L. Adams, Ahmadreza Niavarani, Bahareh Sharififard, Rasoul Aliannejad, Ali Amirsavadkouhi, Zeinab Naderpour, Hengameh Ansari Tadi, Afshar Etemadi Aleagha, Saeideh Ahmadi, Seyed Behrooz Mohseni Moghaddam, Alireza Adamsara, Morteza Saeedi, Hamed Abdollahi, Abdolmajid Hosseini, Pajaree Chariyavilaskul, Monpat Chamnanphon, Thitima B. Suttichet, Vorasuk Shotelersuk, Monnat Pongpanich, Chureerat Phokaew, Wanna Chetruengchai, Watsamon Jantarabenjakul, Opass Putchareon, Pattama Torvorapanit, Thanyawee Puthanakit, Pintip Suchartlikitwong, Nattiya Hirankarn, Voraphoj Nilaratanakul, Pimpayao Sodsai, Ben M. Brumpton, Kristian Hveem, Cristen Willer, Wei Zhou, Tormod Rogne, Erik Solligard, Bjørn Olav Åsvold, Malak Abedalthagafi, Manal Alaamery, Saleh Alqahtani, Dona Baraka, Fawz Al Harthi, Ebtehal Alsolm, Leen Abu Safieh, Albandary M. Alowayn, Fatimah Alqubaishi, Amal Al Mutairi, Serghei Mangul, Abdulraheem Alshareef, Mona Sawaji, Mansour Almutairi, Nora Aljawini, Nour Albesher, Yaseen M. Arabi, Ebrahim S. Mahmoud, Amin K. Khattab, Roaa T. Halawani, Ziab Z. Alahmadey, Jehad K. Albakri, Walaa A. Felemban, Bandar A. Suliman, Rana Hasanato, Laila Al-Awdah, Jahad Alghamdi, Deema AlZahrani, Sameera AlJohani, Hani Al-Afghani, May Alrashed, Nouf AlDhawi, Hadeel AlBardis, Sarah Alkwai, Moneera Alswailm, Faisal Almalki, Maha Albeladi, Iman Almohammed, Eman Barhoush, Anoud Albader, Salam Massadeh, Abdulaziz AlMalik, Sara Alotaibi, Bader Alghamdi, Junghyun Jung, Mohammad S. Fawzy, Yunsung Lee, Per Magnus, Lill-Iren S. Trogstad, Øyvind Helgeland, Jennifer R. Harris, Massimo Mangino, Tim D. Spector, Duncan Emma, Sandra P. Smieszek, Bartlomiej P. Przychodzen, Christos Polymeropoulos, Vasilios Polymeropoulos, Mihael H. Polymeropoulos, Israel Fernandez-Cadenas, Jordi Perez-Tur, Laia Llucià-Carol, Natalia Cullell, Elena Muiño, Jara Cárcel-Márquez, Marta L. DeDiego, Lara Lloret Iglesias, Anna M. Planas, Alex Soriano, Veronica Rico, Daiana Agüero, Josep L. Bedini, Francisco Lozano, Carlos Domingo, Veronica Robles, Francisca Ruiz-Jaén, Leonardo Márquez, Juan Gomez, Eliecer Coto, Guillermo M. Albaiceta, Marta García-Clemente, David Dalmau, Maria J. Arranz, Beatriz Dietl, Alex Serra-Llovich, Pere Soler, Roger Colobrán, Andrea Martín-Nalda, Alba Parra Martínez, David Bernardo, Silvia Rojo, Aida Fiz-López, Elisa Arribas, Paloma de la Cal-Sabater, Tomás Segura, Esther González-Villa, Gemma Serrano-Heras, Joan Martí-Fàbregas, Elena Jiménez-Xarrié, Alicia de Felipe Mimbrera, Jaime Masjuan, Sebastian García-Madrona, Anna Domínguez-Mayoral, Joan Montaner Villalonga, Paloma Menéndez-Valladares, Daniel I. Chasman, Julie E. Buring, Paul M. Ridker, Giulianini Franco, Howard D. Sesso, JoAnn E. Manson, Joseph R. Glessner, Carolina Medina-Gomez, Andre G. Uitterlinden, M. Arfan Ikram, Kati Kristiansson, Sami Koskelainen, Markus Perola, Kati Donner, Katja Kivinen, Aarno Palotie, Samuli Ripatti, Sanni Ruotsalainen, Mari Kaunisto, null FinnGen, Tomoko Nakanishi, Guillaume Butler-Laporte, Vincenzo Forgetta, David R. Morrison, Biswarup Ghosh, Laetitia Laurent, Alexandre Belisle, Danielle Henry, Tala Abdullah, Olumide Adeleye, Noor Mamlouk, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk Branka Vulesevic, Meriem Bouab, Charlotte Guzman, Louis Petitjean, Chris Tselios, Xiaoqing Xue, Erwin Schurr, Jonathan Afilalo, Marc Afilalo, Maureen Oliveira, Bluma Brenner, Pierre Lepage, Jiannis Ragoussis, Daniel Auld, Nathalie Brassard, Madeleine Durand, Michaël Chassé, Daniel E. Kaufmann, G. Mark Lathrop, Vincent Mooser, J. Brent Richards, Rui Li, Darin Adra, Souad Rahmouni, Michel Georges, Michel Moutschen, Benoit Misset, Gilles Darcis, Julien Guiot, Julien Guntz, Samira Azarzar, Stéphanie Gofflot, Yves Beguin, Sabine Claassen, Olivier Malaise, Pascale Huynen, Christelle Meuris, Marie Thys, Jessica Jacques, Philippe Léonard, Frederic Frippiat, Jean-Baptiste Giot, Anne-Sophie Sauvage, Christian Von Frenckell, Yasmine Belhaj, Bernard Lambermont, Sara Pigazzini, Lindokuhle Nkambule, Michelle Daya, Jonathan Shortt, Nicholas Rafaels, Stephen J. Wicks, Kristy Crooks, Kathleen C. Barnes, Christopher R. Gignoux, Sameer Chavan, Triin Laisk, Kristi Läll, Maarja Lepamets, Reedik Mägi, Tõnu Esko, Ene Reimann, Lili Milani, Helene Alavere, Kristjan Metsalu, Mairo Puusepp, Andres Metspalu, Paul Naaber, Edward Laane, Jaana Pesukova, Pärt Peterson, Kai Kisand, Jekaterina Tabri, Raili Allos, Kati Hensen, Joel Starkopf, Inge Ringmets, Anu Tamm, Anne Kallaste, Pierre-Yves Bochud, Carlo Rivolta, Stéphanie Bibert, Mathieu Quinodoz, Dhryata Kamdar, Noémie Boillat, Semira Gonseth Nussle, Werner Albrich, Noémie Suh, Dionysios Neofytos, Véronique Erard, Cathy Voide, null FHoGID, null RegCOVID, null P-PredictUs, null SeroCOVID, null CRiPSI, Rafael de Cid, Iván Galván-Femenía, Natalia Blay, Anna Carreras, Beatriz Cortés, Xavier Farré, Lauro Sumoy, Victor Moreno, Josep Maria Mercader, Marta Guindo-Martinez, David Torrents, Manolis Kogevinas, Judith Garcia-Aymerich, Gemma Castaño-Vinyals, Carlota Dobaño, Alessandra Renieri, Francesca Mari, Chiara Fallerini, Sergio Daga, Elisa Benetti, Margherita Baldassarri, Francesca Fava, Elisa Frullanti, Floriana Valentino, Gabriella Doddato, Annarita Giliberti, Rossella Tita, Sara Amitrano, Mirella Bruttini, Susanna Croci, Ilaria Meloni, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Giada Beligni, Andrea Tommasi, Laura Di Sarno, Maria Palmieri, Miriam Lucia Carriero, Diana Alaverdian, Stefano Busani, Raffaele Bruno, Marco Vecchia, Mary Ann Belli, Nicola Picchiotti, Maurizio Sanarico, Marco Gori, Simone Furini, Stefania Mantovani, Serena Ludovisi, Mario Umberto Mondelli, Francesco Castelli, Eugenia Quiros-Roldan, Melania Degli Antoni, Isabella Zanella, Massimo Vaghi, Stefano Rusconi, Matteo Siano, Francesca Montagnani, Arianna Emiliozzi, Massimiliano Fabbiani, Barbara Rossetti, Elena Bargagli, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli, David Bennett, Federico Anedda, Simona Marcantonio, Sabino Scolletta, Federico Franchi, Maria Antonietta Mazzei, Susanna Guerrini, Edoardo Conticini, Luca Cantarini, Bruno Frediani, Danilo Tacconi, Chiara Spertilli, Marco Feri, Alice Donati, Raffaele Scala, Luca Guidelli, Genni Spargi, Marta Corridi, Cesira Nencioni, Leonardo Croci, Maria Bandini, Gian Piero Caldarelli, Paolo Piacentini, Elena Desanctis, Silvia Cappelli, Anna Canaccini, Agnese Verzuri, Valentina Anemoli, Agostino Ognibene, Alessandro Pancrazzi, Maria Lorubbio, Antonella D’Arminio Monforte, Federica Gaia Miraglia, Massimo Girardis, Sophie Venturelli, Andrea Cossarizza, Andrea Antinori, Alessandra Vergori, Arianna Gabrieli, Agostino Riva, Daniela Francisci, Elisabetta Schiaroli, Francesco Paciosi, Pier Giorgio Scotton, Francesca Andretta, Sandro Panese, Renzo Scaggiante, Francesca Gatti, Saverio Giuseppe Parisi, Stefano Baratti, Matteo Della Monica, Carmelo Piscopo, Mario Capasso, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Giuseppe Fiorentino, Massimo Carella, Marco Castori, Giuseppe Merla, Gabriella Maria Squeo, Filippo Aucella, Pamela Raggi, Carmen Marciano, Rita Perna, Matteo Bassetti, Antonio Di Biagio, Maurizio Sanguinetti, Luca Masucci, Serafina Valente, Marco Mandalà, Alessia Giorli, Lorenzo Salerni, Patrizia Zucchi, Pierpaolo Parravicini, Elisabetta Menatti, Tullio Trotta, Ferdinando Giannattasio, Gabriella Coiro, Fabio Lena, Domenico A. Coviello, Cristina Mussini, Enrico Martinelli, Sandro Mancarella, Luisa Tavecchia, Lia Crotti, Chiara Gabbi, Marco Rizzi, Franco Maggiolo, Diego Ripamonti, Tiziana Bachetti, Maria Teresa La Rovere, Simona Sarzi-Braga, Maurizio Bussotti, Stefano Ceri, Pietro Pinoli, Francesco Raimondi, Filippo Biscarini, Alessandra Stella, Kristina Zguro, Katia Capitani, Claudia Suardi, Simona Dei, Gianfranco Parati, Sabrina Ravaglia, Rosangela Artuso, Giordano Bottà, Paolo Di Domenico, Ilaria Rancan, Antonio Perrella Francesco Bianchi, Davide Romani, Paola Bergomi, Emanuele Catena, Riccardo Colombo, Marco Tanfoni, Antonella Vincenti, Claudio Ferri, Davide Grassi, Gloria Pessina, Mario Tumbarello, Massimo Di Pietro, Ravaglia Sabrina, Sauro Luchi, Chiara Barbieri, Donatella Acquilini, Elena Andreucci, Francesco Vladimiro Segala, Giusy Tiseo, Marco Falcone, Mirjam Lista, Monica Poscente, Oreste De Vivo, Paola Petrocelli, Alessandra Guarnaccia, Silvia Baroni, Albert V. Smith, Andrew P. Boughton, Kevin W. Li, Jonathon LeFaive, Aubrey Annis, Anne E. Justice, Tooraj Mirshahi, Geetha Chittoor, Navya Shilpa Josyula, Jack A. Kosmicki, Manuel A.R. Ferreira, Joseph B. Leader, Dave J. Carey, Matthew C. Gass, Julie E. Horowitz, Michael N. Cantor, Ashish Yadav, Aris Baras, Goncalo R. Abecasis, David A. van Heel, Karen A. Hunt, Dan Mason, Qin Qin Huang, Sarah Finer, null Genes & Health Research Team, Bhavi Trivedi, Christopher J. Griffiths, Hilary C. Martin, John Wright, Richard C. Trembath, Nicole Soranzo, Jing Hua Zhao, Adam S. Butterworth, John Danesh, Emanuele Di Angelantonio, Lude Franke Marike Boezen, Patrick Deelen, Annique Claringbould, Esteban Lopera, Robert Warmerdam, Judith.M. Vonk, Irene van Blokland, Pauline Lanting, Anil P.S. Ori, Brooke Wolford Sebastian Zöllner, Jiongming Wang, Andrew Beck, Gina Peloso, Yuk-Lam Ho, Yan V. Sun, Jennifer E. Huffman, Christopher J. O’Donnell, Kelly Cho, Phil Tsao, J. Michael Gaziano, Michel (M.G.) Nivard, Eco (E.J.C.) de geus, Meike Bartels, Jouke Jan Hottenga, Scott T. Weiss, Elizabeth W. Karlson, Jordan W. Smoller, Robert C. Green, Yen-Chen Anne Feng, Josep Mercader, Shawn N. Murphy, James B. Meigs, Ann E. Woolley, Emma F. Perez, Daniel Rader, Anurag Verma, Marylyn D. Ritchie, Binglan Li, Shefali S. Verma, Anastasia Lucas, Yuki Bradford, Hugo Zeberg, Robert Frithiof, Michael Hultström, Miklos Lipcsey, Lindo Nkambul, Nicolas Tardif, Olav Rooyackers, Jonathan Grip, Tomislav Maricic, Konrad J. Karczewski, Elizabeth G. Atkinson, Kristin Tsuo, Nikolas Baya, Patrick Turley, Rahul Gupta, Shawneequa Callier, Raymond K. Walters, Duncan S. Palmer, Gopal Sarma, Nathan Cheng, Wenhan Lu, Sam Bryant, Claire Churchhouse, Caroline Cusick, Jacqueline I. Goldstein, Daniel King, Cotton Seed, Hilary Finucane, Alicia R. Martin, F. Kyle Satterstrom, Daniel J. Wilson, Jacob Armstrong, Justine K. Rudkin, Gavin Band, Sarah G. Earle, Shang-Kuan Lin, Nicolas Arning, Derrick W. Crook, David H. Wyllie, Anne Marie O’Connell, Chris C.A. Spencer, Nils Koelling, Mark J. Caulfield, Richard H. Scott, Tom Fowler, Loukas Moutsianas, Athanasios Kousathanas, Dorota Pasko, Susan Walker, Augusto Rendon, Alex Stuckey, Christopher A. Odhams, Daniel Rhodes, Georgia Chan, Prabhu Arumugam, Catherine A. Ball, Eurie L. Hong, Kristin Rand, Ahna Girshick, Harendra Guturu, Asher Haug Baltzell, Genevieve Roberts, Danny Park, Marie Coignet, Shannon McCurdy, Spencer Knight, Raghavendran Partha, Brooke Rhead, Miao Zhang, Nathan Berkowitz, Michael Gaddis, Keith Noto, Luong Ruiz, Milos Pavlovic, Laura G. Sloofman, Alexander W. Charney, Noam D. Beckmann, Eric E. Schadt, Daniel M. Jordan, Ryan C. Thompson, Kyle Gettler, Noura S. Abul-Husn, Steven Ascolillo, Joseph D. Buxbaum, Kumardeep Chaudhary, Judy H. Cho, Yuval Itan, Eimear E. Kenny, Gillian M. Belbin, Stuart C. Sealfon, Robert P. Sebra, Irene Salib, Brett L. Collins, Tess Levy, Bari Britvan, Katherine Keller, Lara Tang, Michael Peruggia, Liam L. Hiester, Kristi Niblo, Alexandra Aksentijevich, Alexander Labkowsky, Avromie Karp, Menachem Zlatopolsky, Michael Preuss, Ruth J.F. Loos, Girish N. Nadkarni, Ron Do, Clive Hoggart, Sam Choi, Slayton J. Underwood, Paul O’Reilly, Laura M. Huckins, Marissa Zyndorf, AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Neurology

Subjects
Medical Physiology, Gene Expression, Genome-wide association study, Genome, Severity of Illness Index, colocalization, Gene expression, Databases, Genetic, Ethnicity, 2.1 Biological and endogenous factors, GWAS, Aetiology, Biology (General), Lung, Genetics, Chromosome Mapping, Single Nucleotide, Organ Specificity, Biotechnology, Cell type, QH301-705.5, Quantitative Trait Loci, Single-nucleotide polymorphism, Biology, eQTL, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, Databases, Genetic, SNP, Humans, Genetic Predisposition to Disease, COVID-19 Host Genetics Initiative, Polymorphism, Gene, COVID-19, SARS-CoV-2, Gene Expression Profiling, Prevention, Human Genome, Computational Biology, Genetic Variation, Good Health and Well Being, Expression quantitative trait loci, Biochemistry and Cell Biology, Transcriptome, Genome-Wide Association Study
Abstract

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types., Graphical abstract, D’Antonio et al. characterize associations between GWAS signals for COVID-19 disease and eQTLs in 69 human tissues to identify causal variants and their underlying molecular mechanisms. They show that diverse symptoms and disease severity of COVID-19 are associated with variants affecting gene expression in a wide variety of tissues.

Published
2022
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14. Risk Factors for Mortality in Hospitalized Coronavirus Disease 2019 Patients

Author

Tere Moreno-López, Franklyn Ferney Meza, Ana Martínez-Urrea, Gemma Grau, Lucía Boix-Palop, Maria José de la Asunción, Esther Calbo, Komal Malik, Josep Trenado, Pablo Martínez-Camblor, Lluis Simón-Pascua, Laura Martinez, Lucía Gómez, Siena Molina, Oriol Llargués, Bienvenido Barreiro, Cristina Castrillo, Aina Mateu, Pere Almagro, David Clemente, Ginebra Libori-Roch, Mireia Cairó, Laura M. Gisbert, and Beatriz Dietl

Subjects
Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, China, Fatal outcome, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, medicine.disease, Critical Care and Intensive Care Medicine, Virology, Pneumonia, Risk Factors, Pandemic, Correspondence, medicine, Humans, business, Cardiology and Cardiovascular Medicine
Published
2020
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15. Improvement of pneumococcal pneumonia diagnosis using quantitative real-time PCR targeting lytA in adult patients: a prospective cohort study

Author

Esther Calbo, Beatriz Dietl, Lucía Boix-Palop, J. R. Perez, M. Xercavins, Javier Garau, Ester Picó-Plana, Meritxell Obradors, and Lydia Canales

Subjects
Adult, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Pneumonia severity index, medicine.medical_treatment, 030106 microbiology, Urine, Real-Time Polymerase Chain Reaction, medicine.disease_cause, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Nasopharynx, Internal medicine, Streptococcus pneumoniae, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Mechanical ventilation, business.industry, General Medicine, Pneumonia, Pneumococcal, medicine.disease, Intensive care unit, Community-Acquired Infections, Pneumonia, Infectious Diseases, Pneumococcal pneumonia, business
Abstract

Objectives The aim of the study was to assess the performance of real-time PCR targeting the lytA gene (rtPCR-lytA) in plasma, urine and nasopharyngeal (NP) samples for the diagnosis of pneumococcal community-acquired pneumonia (P-CAP). Methods Prospective observational study including all consecutive adults with CAP from November 2015 to May 2017. P-CAP was defined if pneumococcus was identified using conventional methods (CM) and/or a positive rtPCR-lytA was detected in blood, urine or NP samples (NP cut-off ≥8000 copies/mL). Diagnostic performance of each test was calculated. Results A total of 133 individuals with CAP were included. Of these, P-CAP was diagnosed in 62 (46.6%). The proportion of P-CAP diagnosed by rtPCR-lytA methods was significantly higher than that diagnosed by CM (87.1% versus 59.7%, p 0.005). The rtPCR-lytA identified Streptococcus pneumoniae in 25 patients (40.3% of all individuals with P-CAP) whose diagnosis would have been missed by CM. NP-rtPCR-lytA allowed diagnosis of 62.3% of P-CAP. A nasopharyngeal colonization density ≥2351 copies/mL predicted P-CAP diagnosis (area under the curve = 0.82, sensitivity 83.3%, specificity 80.9%). There was a positive correlation between increasing bacterial load in blood and CURB-65 score (Spearman correlation coefficient r = 0.4, p 0.001), pneumonia severity index (r = 0.3, p 0.02) and time to clinical stability (r = 0.33, p 0.01). Median bacterial load in blood was higher in P-CAP patients with bacteraemia (0.65 × 103 versus 0 × 103 copies/mL, p 0.002), intensive care unit admission (0.68 × 103 versus 0 × 103 copies/mL, p 0.04) or mechanical ventilation (7.45 × 103 versus 0 × 103 copies/mL, p 0.04). Conclusions The use of rtPCR-lytA methods significantly increased the diagnosis of P-CAP compared with CM. Nasopharyngeal swabs rtPCR-lytA detection, with an accurate cut-off value, was the most promising among molecular methods for the diagnosis of P-CAP.

Published
2022
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16. Ceftolozane/tazobactam in the treatment of osteomyelitis and skin and soft-tissue infections due to extensively drug-resistant Pseudomonas aeruginosa : clinical and microbiological outcomes

Author

Lucía Boix-Palop, Esther Calbo, Lucía Gómez, Eva Cuchi, Jordi Nicolás, F.J. González de Molina, I. Sánchez, Beatriz Dietl, and Paula Arcenillas

Subjects
Male, 0301 basic medicine, Microbiology (medical), Tazobactam, medicine.medical_specialty, 030106 microbiology, Penicillanic Acid, Drug resistance, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Drug Resistance, Multiple, Bacterial, Internal medicine, medicine, Humans, Pseudomonas Infections, Pharmacology (medical), 030212 general & internal medicine, Aged, Retrospective Studies, Aged, 80 and over, Antiinfective agent, Pseudomonas aeruginosa, business.industry, Soft Tissue Infections, Osteomyelitis, Skin Diseases, Bacterial, General Medicine, Middle Aged, Antimicrobial, medicine.disease, Anti-Bacterial Agents, Cephalosporins, Multiple drug resistance, Treatment Outcome, Infectious Diseases, Female, Ceftolozane, beta-Lactamase Inhibitors, business, medicine.drug
Abstract

Infections due to multidrug-resistant bacteria (MDR) are currently a clinical challenge, mainly in elderly patients. The antimicrobial spectrum, safety and efficacy of ceftolozane/tazobactam (C/T) make it an attractive option for the treatment of MDR bacterial infections beyond the indications approved to date. Here we report our experience with C/T in four cases of osteomyelitis and three cases of skin and soft-tissue infections due to extensively-drug-resistant Pseudomonas aeruginosa.

Published
2018
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17. RIESGO DE INFECCIÓN DE DISPOSITIVOS INTRACARDÍACOS EN PACIENTES CON BACTERIEMIA TARDÍA. ANÁLISIS EN UN COHORTE NACIONAL

Author

Pedro María Martínez Pérez-Crespo, M. Xercavins, María Luisa Cantón, Esther Calbo, Lucía Boix Palop, Jesús Rodríguez Baño, Beatriz Dietl, and Luis Eduardo López Cortés

Subjects
Gynecology, medicine.medical_specialty, business.industry, lcsh:R, lcsh:Surgery, Medicine, lcsh:Medicine, Surgery, lcsh:RD1-811, Cardiology and Cardiovascular Medicine, business
Published
2020

20. Intoxicación por ayahuasca

Author

Beatriz Dietl Gómez-Luengo and Bernat de Pablo Márquez

Subjects
03 medical and health sciences, 0302 clinical medicine, Traditional medicine, business.industry, Medicine, 030212 general & internal medicine, General Medicine, business, 030217 neurology & neurosurgery
Published
2017
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