The association between interleukin-6 inhibitors as treatment for COVID-19 and mental health problems in ICU survivors

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OBJECTIVE: To assess whether exposure to interleukin-6 (IL-6) inhibitors as treatment for critically ill COVID-19 patients is associated with a lower prevalence of mental health problems one year after ICU admission. DESIGN: Retrospective cohort study using prospectively collected outcome data. SETTING: Two university medical centers in the Netherlands: University Medical Center Utrecht (UMCU) and Radboud University Medical Center (Radboudumc). PATIENTS: Adult ICU survivors admitted to the ICU for COVID-19 from September 1, 2020, to March 31, 2022, with available one-year follow-up data. EXPOSURE: IL-6 inhibitors (tocilizumab or sarilumab) as treatment for COVID-19. MEASUREMENTS AND MAIN RESULTS: Mental health problems were assessed using the Impact of Event Scale (IES-6 or IES-R) for post-traumatic stress disorder (PTSD) and the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression. The primary outcome was a composite of PTSD, anxiety, and/or depression symptoms one year after ICU admission. Among 170 patients included in the primary analysis (119 exposed to IL-6 inhibitors, 51 unexposed), IL-6 inhibitor exposure was associated with a lower prevalence of mental health problems (adjusted odds ratio (aOR) 0.46, 95% confidence interval (CI) 0.22-0.93) and PTSD symptoms alone (aOR 0.45, 95% CI 0.20-0.97). No significant associations were found for anxiety (aOR 0.77, 95% CI 0.34-1.72) or depression (aOR 0.71, 95% CI 0.33-1.50) symptoms alone. CONCLUSIONS: Exposure to IL-6 inhibitors as treatment for critically ill COVID-19 patients was associated with a lower prevalence of mental health problems, primarily driven by a lower prevalence of PTSD symptoms, one year after ICU admission. These findings suggest a potential role for cytokine-targeted therapies in mitigating long-term mental health problems in ICU survivors, but further research is needed to establish causality. KEY POINTS: Question: Does treatment with interleukin-6 (IL-6) inhibitors during ICU admission for COVID-19 reduce the prevalence of mental health problems one year later? FINDINGS: In this multicenter cohort study of 170 COVID-19 ICU survivors, IL-6 inhibitor exposure was associated with a significantly lower prevalence of PTSD and of the composite outcome of PTSD, anxiety, or depression symptoms one year after ICU admission. Meaning: These findings suggest that IL-6 inhibition during critical illness may help mitigate long-term psychological burden in ICU survivors.

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