The Effect of IL-6 Inhibitors on Mortality Among Hospitalized COVID-19 Patients: A Multicenter Study

J Infect Dis. 2021 Feb 24;223(4):581-588. doi: 10.1093/infdis/jiaa717.


Background: The effectiveness of interleukin-6 inhibitors (IL-6i) in ameliorating coronavirus disease 2019 (COVID-19) remains uncertain.

Methods: We analyzed data for patients aged ≥18 years admitted with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test at 4 safety-net hospital systems with diverse populations and high rates of medical comorbidities in 3 US regions. We used inverse probability of treatment weighting via machine learning for confounding adjustment by demographics, comorbidities, and disease severity markers. We estimated the average treatment effect, the odds of IL-6i effect on in-hospital mortality from COVID-19, using a logistic marginal structural model.

Results: Of 516 patients, 104 (20.1%) received IL-6i. Estimate of the average treatment effect adjusted for confounders suggested a 37% reduction in odds of in-hospital mortality in those who received IL-6i compared with those who did not, although the confidence interval included the null value of 1 (odds ratio = 0.63; 95% confidence interval, .29-1.38). A sensitivity analysis suggested that potential unmeasured confounding would require a minimum odds ratio of 2.55 to nullify our estimated IL-6i effect size.

Conclusions: Despite low precision, our findings suggested a relatively large effect size of IL-6i in reducing the odds of COVID-19-related in-hospital mortality.

Keywords: COVID-19; cytokine release syndrome; interleukin 6 inhibitors.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • COVID-19 / mortality
  • COVID-19 Drug Treatment*
  • Comorbidity
  • Female
  • Hospital Mortality*
  • Hospitalization
  • Humans
  • Interleukin-6 / antagonists & inhibitors*
  • Logistic Models
  • Male
  • Middle Aged
  • Retrospective Studies
  • Severity of Illness Index
  • Treatment Outcome
  • United States / epidemiology


  • Antibodies, Monoclonal, Humanized
  • Interleukin-6