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

https://doi.org/10.1016/j.jaci.2020.09.018Get rights and content

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.

Key words

COVID-19
IL-6
tocilizumab
invasive mechanical ventilation

Abbreviations used

ARDS
Acute respiratory distress syndrome
CAR
Chimeric antigen receptor
COPD
Chronic obstructive pulmonary disease
COVID-19
Coronavirus disease 2019
CRP
C-reactive protein
FiO2
Fraction of inspired oxygen
IL-6R
IL-6 receptor
IMV
Invasive mechanical ventilation
IQR
Interquartile range
LDH
Lactate dehydrogenase
PaO2
Arterial oxygen tension
ROC
Receiver-operating characteristic
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
TCZ
Tocilizumab

Cited by (0)

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.

These authors contributed equally to this work.

These authors share senior authorship.

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See the Acknowledgments section at the end of the article for the REINMUN-COVID Group.

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