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

Galván-Román, José María; Rodríguez-García, Sebastián C.; Roy-Vallejo, Emilia; Marcos-Jiménez, Ana; Sánchez-Alonso, Santiago; Fernández-Díaz, Carlos; Alcaraz-Serna, Ana; Mateu-Albero, Tamara; Rodríguez-Cortes, Pablo; Sánchez-Cerrillo, Ildefonso; Esparcia, Laura; Martínez-Fleta, Pedro; López-Sanz, Celia; Gabrie, Ligia; Guerola, Luciana del Campo; Suarez, Carmen; Ancochea, Julio; Canabal, Alfonso; Albert, Patricia; Rodríguez-Serrano, Diego A.; Aguilar, Juan Mariano; Arco, Carmen del; Santos, Ignacio de los; García-Fraile, Lucio; Camara, Rafael de la; Serra, José María; Ramírez, Esther; Alonso, Tamara; Landete, Pedro; Soriano, Joan B.; Martín-Gayo, Enrique; Torres, Arturo Fraile; Zurita Cruz, Nelly Daniela; García-Vicuña, Rosario; Cardeñoso, Laura; Sánchez-Madrid, Francisco; Alfranca, Arantzazu; Muñoz-Calleja, Cecilia; González-Álvaro, Isidoro

Background COVID-19 patients can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation (IMV). Since interleukin-6 (IL-6) is a relevant cytokine in ARDS, the blockade of its receptor with Tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective To determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods Retrospective observational study performed in hospitalized patients diagnosed of COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with pre- and post-administration 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 (PaO2/FiO2) or mortality. Results One hundred and forty-six patients were studied, predominantly male (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels>30 pg/ml was the best predictor for IMV (OR:7.1; p<0.001). Early administration of TCZ was associated with improvement of oxygenation (PaO2/FiO2) in patients with high IL-6 (p=0.048). Patients with high IL-6 not treated with TCZ showed high mortality (HR: 4.6; p=0.003), as well as those with low IL-6 treated with TCZ (HR: 3.6; p=0.016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusion Baseline IL-6>30 pg/ml predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.