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

      research-article
      , MD 1 , , , MD 2 , , , MD 1 , , MSc 3 , , MSc 3 , , MD 2 , , MD 3 , , MSc 3 , , MD 1 , , MD 3 , , BSc 3 , , MSc 3 , , BSc 3 , , MD 3 , , MD 3 , , MD Prof 1 , , MD Prof 4 , , MD/PhD 5 , , MD/PhD 5 , , MD/PhD 5 , , MD/PhD 6 , , MD/PhD 6 , , MD/PhD 1 , , MD 1 , , MD/PhD 7 , , Pharm 8 , , PharmD 8 , , MD 4 , , MD/PhD 4 , , MD/PhD 4 , , PhD 3 , , Pharm 9 , , Pharm 9 , , MD/PhD 2 , , MD/PhD 9 , , Prof 3 , , MD/PhD 3 , $ , 3 , $ , , MD/PhD 2 , ∗∗ , $ , REINMUN-COVID group
      The Journal of Allergy and Clinical Immunology
      American Academy of Allergy, Asthma & Immunology
      COVID-19, Interleukin-6, Tocilizumab, Invasive Mechanical Ventilation, AEMPS, Spanish Agency for Drugs and Health Devices, ARDS, acute respiratory distress syndrome, AUC, Area under curve, CAR, chimeric antigen receptor, COPD, chronic obstructive pulmonary disease, COVID-19, coronavirus disease 2019, CRP, C-reactive protein, CRS, cytokine release syndrome, IL, interleukin, IMV, invasive mechanical ventilation, IQR, interquartile range, LR+, positive likelihood ratio, LR, negative likelihood ratio, PaO2, arterial oxygen tension, PaO2/FiO2, arterial oxygen tension/fraction of inspired oxygen ratio, PCT, procalcitonin, ROC, receiver operating characteristic, SatO2, mean oxygen saturation, SD, standard deviation, STROBE, Strengthening the Reporting of Observational Studies in Epidemiology, TCZ, Tocilizumab, TNF, tumor necrosis factor

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          Abstract

          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 (PaO 2/FiO 2) 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 (PaO 2/FiO 2) 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.

          Abstract

          Baseline IL-6 serum levels>30 pg/ml identify severe COVID-19 patients and should be used to guide the intervention with IL-6R inhibitors, aiming to improve their use in an uncertain and evolving therapeutic scenario.

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          Author and article information

          Contributors
          Role: Prof
          Journal
          J Allergy Clin Immunol
          J. Allergy Clin. Immunol
          The Journal of Allergy and Clinical Immunology
          American Academy of Allergy, Asthma & Immunology
          0091-6749
          1097-6825
          30 September 2020
          30 September 2020
          Affiliations
          [1 ]Internal Medicine Service
          [2 ]Rheumatology Service
          [3 ]Immunology Service
          [4 ]Pneumology Service
          [5 ]Intensive Care Unit
          [6 ]Emergency Service
          [7 ]Hematology Service
          [8 ]Hospital Pharmacy Service
          [9 ]Microbiology Service. Hospital Universitario de la Princesa. Universidad Autónoma Madrid. Instituto de Investigación Sanitaria Princesa (IIS-IP)
          Author notes
          [∗∗ ]Author for correspondence Isidoro González-Alvaro. Rheumatology Service. Hospital Universitario de la Princesa. Instituto de Investigación Sanitaria Princesa (IIS-IP). c/Diego de León 62, 28006 - Madrid. Spain phone: (+34) 650 17 94 41
          [∗]

          These authors have contributed equally

          [$]

          These authors share senior authorship

          Article
          S0091-6749(20)31329-4
          10.1016/j.jaci.2020.09.018
          7525244
          33010257
          6fdf51a2-396b-4584-b456-86d083191041
          © 2020 American Academy of Allergy, Asthma & Immunology.

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

          History
          : 29 May 2020
          : 7 September 2020
          : 17 September 2020
          Categories
          Article

          Immunology
          covid-19,interleukin-6,tocilizumab,invasive mechanical ventilation,aemps, spanish agency for drugs and health devices,ards, acute respiratory distress syndrome,auc, area under curve,car, chimeric antigen receptor,copd, chronic obstructive pulmonary disease,covid-19, coronavirus disease 2019,crp, c-reactive protein,crs, cytokine release syndrome,il, interleukin,imv, invasive mechanical ventilation,iqr, interquartile range,lr+, positive likelihood ratio,lr, negative likelihood ratio,pao2, arterial oxygen tension,pao2/fio2, arterial oxygen tension/fraction of inspired oxygen ratio,pct, procalcitonin,roc, receiver operating characteristic,sato2, mean oxygen saturation,sd, standard deviation,strobe, strengthening the reporting of observational studies in epidemiology,tcz, tocilizumab,tnf, tumor necrosis factor

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