IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

被引:151
|
作者
Maria Galvan-Roman, Jose [1 ]
Rodriguez-Garcia, Sebastian C. [2 ]
Roy-Vallejo, Emilia [1 ]
Marcos-Jimenez, Ana [3 ]
Sanchez-Alonso, Santiago [3 ]
Fernandez-Diaz, Carlos [2 ]
Alcaraz-Serna, Ana [3 ]
Mateu-Albero, Tamara [3 ]
Rodriguez-Cortes, Pablo [1 ]
Sanchez-Cerrillo, Ildefonso [3 ]
Esparcia, Laura [3 ]
Martinez-Fleta, Pedro [3 ]
Lopez-Sanz, Celia [3 ]
Gabrie, Ligia [3 ]
del Campo Guerola, Luciana [3 ]
Suarez-Fernandez, Carmen [1 ]
Ancochea, Julio [4 ]
Canabal, Alfonso [5 ]
Albert, Patricia [5 ]
Rodriguez-Serrano, Diego A. [5 ]
Mariano Aguilar, Juan [6 ]
del Arco, Carmen [6 ]
de los Santos, Ignacio [1 ]
Garcia-Fraile, Lucio [1 ]
de la Camara, Rafael [7 ]
Maria Serra, Jose [8 ]
Ramirez, Esther [8 ]
Alonso, Tamara [4 ]
Landete, Pedro [4 ]
Soriano, Joan B. [4 ]
Martin-Gayo, Enrique [3 ]
Fraile Torres, Arturo [9 ]
Zurita Cruz, Nelly Daniela [9 ]
Garcia-Vicuna, Rosario [2 ]
Cardenoso, Laura [9 ]
Sanchez-Madrid, Francisco [3 ,10 ]
Alfranca, Arantzazu [3 ]
Munoz-Calleja, Cecilia [3 ]
Gonzalez-Alvaro, Isidoro [2 ]
机构
[1] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Internal Med Serv, Madrid, Spain
[2] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Rheumatol Serv, Madrid, Spain
[3] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Immunol Serv, Madrid, Spain
[4] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Serv Pneumol, Madrid, Spain
[5] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Intens Care Unit, Madrid, Spain
[6] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Emergency Serv, Madrid, Spain
[7] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Hematol Serv, Madrid, Spain
[8] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Hosp Pharm Serv, Madrid, Spain
[9] Univ Autonoma Madrid, Hosp Univ Princesa, Inst Invest Sanitaria Princesa IIS IP, Microbiol Serv, Madrid, Spain
[10] Inst Salud Carlos III ISCIII, Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
关键词
COVID-19; IL-6; tocilizumab; invasive mechanical ventilation;
D O I
10.1016/j.jaci.2020.09.018
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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.
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页码:72 / +
页数:17
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