IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study - 09/01/21
Doi : 10.1016/j.jaci.2020.09.018
José María Galván-Román, MD a, ∗, Sebastián C. Rodríguez-García, MD b, ∗, Emilia Roy-Vallejo, MD a, Ana Marcos-Jiménez, MSc c, Santiago Sánchez-Alonso, MSc c, Carlos Fernández-Díaz, MD b, Ana Alcaraz-Serna, MD c, Tamara Mateu-Albero, MSc c, Pablo Rodríguez-Cortes, MD a, Ildefonso Sánchez-Cerrillo, MD c, Laura Esparcia, BSc c, Pedro Martínez-Fleta, MSc c, Celia López-Sanz, BSc c, Ligia Gabrie, MD c, Luciana del Campo Guerola, MD c, Carmen Suárez-Fernández, MD, PhD a, Julio Ancochea, MD, PhD d, Alfonso Canabal, MD, PhD e, Patricia Albert, MD, PhD e, Diego A. Rodríguez-Serrano, MD, PhD e, Juan Mariano Aguilar, MD, PhD f, Carmen del Arco, MD, PhD f, Ignacio de los Santos, MD, PhD a, Lucio García-Fraile, MD a, Rafael de la Cámara, MD, PhD g, José María Serra, Pharm h, Esther Ramírez, PharmD h, Tamara Alonso, MD d, Pedro Landete, MD, PhD d, Joan B. Soriano, MD, PhD d, Enrique Martín-Gayo, PhD c, Arturo Fraile Torres, Pharm i, Nelly Daniela Zurita Cruz, Pharm i, Rosario García-Vicuña, MD, PhD b, Laura Cardeñoso, MD, PhD i, Francisco Sánchez-Madrid, PhD c, j, Arantzazu Alfranca, MD, PhD c, ‡, Cecilia Muñoz-Calleja, MD, PhD c, ‡, Isidoro González-Álvaro, MD, PhD b, ⁎, ‡ 
on behalf of the
on behalf of the
REINMUN-COVID Group§
Teresa Alvarado, Pablo Martínez, Francisco Javier de la Cuerda Llorente, Carmen del Arco, Juan Mariano Aguilar, Natalia Villalba, Mónica Negro, Elvira Contreras, Ana del Rey, Cristina Santiago, Manuel Junquera, Raquel Caminero, Francisco Javier Val, Sonia González, Marta Caño, Isabel López, Andrés von Wernitz, Bárbara Retana, Iñigo Guerra, Jorge Sorando, Lydia Chao, María José Cárdenas, Verónica Espiga, Pablo Chicharro, Pedro Rodríguez, Iñigo Hernando Alday, Miguel Sampedro, Jorge Prada, Eukene Rojo Aldama, Yolanda Real, María Caldas, Sergio Casabona, Aitor Lanas-Gimeno, Rafael de la Camara, Angela Figuera Alvárez, Beatriz Aguadol, Alberto Morell, Esther Ramírez, Amparo Ibáñez Zurriaga, María Pérez Abanades, Silvia Ruiz García, Tomás Gallego Aranda, María Ruiz, Concepción Martínez Nieto, José María Serra, Francisco Sánchez-Madrid, Cecilia Muñoz-Calleja, Arantzazu Alfranca, Javier Aspa, Ana Marcos-Jiménez, Santiago Sánchez-Alonso, Ana Alcaraz-Serna, Tamara Mateu-Albero, Ildefonso Sánchez-Cerrillo, Laura Esparcia, Pedro Martínez-Fleta, Celia López-Sanz, Ligia Gabrie, Luciana del Campo Guerola, Elena Fernández, Ma José Calzada, Reyes Tejedor, Alfonso Canabal, Patricia Albert, Diego A. Rodríguez-Serrano, Judit Iglesias, Fernando Suarez, Juan Antonio Sánchez, Beatriz Abad, Carmen Suarez, Ignacio de los Santos, José María Galván-Román, Emilia Roy, Pablo Rodríguez-Cortes, Lucio García-Fraile, Jesus Sanz, Eduardo Sanchez, Fernando Moldenhauer, Pedro Casado, Jose Curbelo, Angela Gutierrez, Azucena Bautista, Nuria Ruiz Giménez, Angelica Fernandez, Pedro Parra, Berta Moyano, Ana Barrios, Diego Real de Asua, Beatriz Sanchez, Carmen Saez, Marianela Ciudad, Desiré Navas, Laura Cardeñoso Domingo, María del Carmen Cuevas Torresano, Diego Domingo García, Teresa Alarcón Cavero, Alicia García Blanco, Alexandra Martín Ramírez, María Auxiliadora Semiglia Chong, Ainhoa Gutiérrez Cobos, Nelly Daniela Zurita Cruz, Arturo Manuel Fraile Torres, Carmen Sanchez-Gonzalez, Antonio Fernádez Perpén, Carolina Díaz Pérez, Julio Ancochea, Tamara Alonso, Pedro Landete, Joan Soriano, Carolina Cisneros, Elena García Castillo, Francisco Javier García Pérez, Rosa María Girón, Celeste Marcos, Enrique Zamora, Patricia García García, Santos Castañeda, Rosario García-Vicuña, Isidoro González-Álvaro, Sebastián Rodríguez-García, Carlos Fernández-Díaz, Irene Llorente Cubas, Eva G. Tomero, Noelia García Castañeda, Ana Ma Ortiz, Cristina Valero, Miren Uriarte, Nuria Montes
a Internal Medicine Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
b Rheumatology Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
c Immunology Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
d Pneumology Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
e Intensive Care Unit, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
f Emergency Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
g Hematology Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
h Hospital Pharmacy Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
i Microbiology Service, Hospital Universitario de la Princesa, Universidad Autónoma Madrid, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
j Centro de Investigación Biomédica en Red - Enfermedades Cardiovasculares (CIBER CV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
∗Corresponding author: Isidoro González-Álvaro, MD, PhD, Rheumatology Service, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), c/Diego de León 62, 28006 Madrid, Spain.Rheumatology ServiceHospital Universitario de la PrincesaInstituto de Investigación Sanitaria Princesa (IIS-IP)c/Diego de León 62Madrid28006Spain
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Abstract |
Background |
Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19.
Objective |
We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ.
Methods |
A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality.
Results |
One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients.
Conclusions |
Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.
Il testo completo di questo articolo è disponibile in PDF.Key words : COVID-19, IL-6, tocilizumab, invasive mechanical ventilation
Abbreviations used : ARDS, CAR, COPD, COVID-19, CRP, FiO2, IL-6R, IMV, IQR, LDH, PaO2, ROC, SARS-CoV-2, TCZ
Mappa
| This study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by “La Caixa Banking Foundation” (grant no. HR17-00016 to F.S.-M.) and “Fondos Supera COVID19” by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. |
|
| Disclosure of potential conflict of interest: S. de la C. Rodríguez-García reports grants from Spanish Rheumatology Foundation, during the conduct of the study; nonfinancial support from Roche, Lilly, Pfizer, and Abbvie; personal fees and nonfinancial support from Novartis, Sanofi, and MSD and from UCB-Pharma, outside the submitted work. C. Fernández-Díaz reports personal fees from BMS and nonfinancial support from Novartis, outside the submitted work. J. Ancochea reports grants and personal fees from GlaxoSmithKline and Boehringer Ingelheim; grants from Linde Healthcare; and grants, personal fees, and nonfinancial support from Roche and from Chiesi, outside the submitted work. D. A. Rodríguez-Serrano reports personal fees from MSD, outside the submitted work. R. de la Camara reports personal fees from MSD, ASTELLAS, Clinigen, Janssen, Roche, and IQONE Health Care outside the submitted work. R. García-Vicuña reports grants, personal fees, and nonfinancial support from Abbvie, BMS, Lilly, Novartis, Sanofi, Sandoz, and MSD; personal fees from Biogen and Celltrion and from Mylan, outside the submitted work; personal fees and nonfinancial support from Pfizer; grants from Roche; and grants and personal fees from Janssen. C. Suarez-Fernández reports personal fees from Bayer, BMS, Daichi Sankyo, MSD, and Pfizer, outside the submitted work. C. Muñoz-Calleja reports competitive grants from Instituto de Salud Carlos III during the conduct of the study. I. González-Álvaro reports grants from Instituto de Salud Carlos III, during the course of the study; personal fees from Lilly and Sanofi; personal fees and nonfinancial support from BMS and Abbvie; research support, personal fees, and nonfinancial support from Roche Laboratories; and nonfinancial support from MSD, Pfizer, and Novartis, not related to the submitted work. The rest of the authors declare that they have no relevant conflicts of interests. |
© 2020
American Academy of Allergy, Asthma & Immunology. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
Vol 147 - N° 1
P. 72 - Gennaio 2021 Ritorno al numero
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