The interleukin-6 (IL-6) receptor is a type-I cytokine receptor that is essential for regulating cell growth and the body’s immune response. IL-6 receptors trigger a pro-inflammatory response that can lead to severe reactions from the immune system. Blocking these receptors can therefore reduce the damage caused by strong immune reactions [1]. Given that viruses like SARS-CoV-2 induce immune system responses that lead to disease symptoms and adverse physiological effects, new research suggests that inhibiting IL-6 receptors can improve outcomes for certain patients with severe cases of COVID-19.
IL-6 receptor blockers have been used in several cases where pro-inflammatory reactions could be deadly. Tocilizumab, an IL-6 receptor antibody, has been used for several years to help patients with autoimmune diseases like rheumatoid arthritis. By inactivating the IL-6 receptor, tocilizumab can reduce the receptor’s pro-inflammatory response, thereby alleviating patients’ symptoms [1].
COVID-19 is often associated with hyperinflammation, which has led many researchers to study the impact of IL-6 antagonists like tocilizumab on patients with the disease. Early trials failed to find a significant mortality benefit from the use of tocilizumab in patients with COVID-19 [2]. However, as Gupta notes in a commentary in The Lancet, these early studies tended to have a fairly small sample size and included patients with varying disease severity [3].
A more recent study by Gordon et. al examined around 800 patients who were on organ support due to COVID-19. Patients who received IL-6 receptor antagonists experienced between 10 and 11 days off of organ support, compared to 0 days in the control group. The researchers therefore concluded that IL-6 receptor antagonists significantly improved outcomes, including survival, for patients in critical condition [4].
Other studies have examined the impacts of IL-6 receptor antagonists in COVID-19 patients who are not critically ill but are from marginalized groups. Salama et. al used a sample of largely minority patients who were hospitalized for COVID-19 but were not on mechanical ventilation. Those that received IL-6 receptor antagonists were 7.3% less likely to be on a ventilator or pass away at the end of the 28-day period. However, the researchers found that while IL-6 receptor antagonists were effective in reducing progression of the disease to mechanical ventilation or death, it did not improve overall survival [5].
The potential impacts from this new research are significant. Previously, only glucocorticoids are known to reduce mortality among patients critically ill with COVID-19 [6]. However, new studies suggest that IL-6 receptor antagonists can reduce mortality among patients with severe cases of COVID-19 and can inhibit progression of the disease in patients with less severe cases. While research on the topic remains limited and in its early stages, IL-6 receptor antagonists are a promising tool in the global fight against COVID-19.
Resources
[1] Wolf, Janina, et al. “Interleukin-6 and Its Receptors: A Highly Regulated and Dynamic System.” Cytokine, vol. 70, no. 1, 2014, pp. 11–20., doi:10.1016/j.cyto.2014.05.024.
[2] Stone, John H., et al. “Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.” New England Journal of Medicine, vol. 383, no. 24, 2020, pp. 2333–2344., doi:10.1056/nejmoa2028836.
[3] Gupta, Shruti, and David E. Leaf. “Tocilizumab in COVID-19: Some Clarity amid Controversy.” The Lancet, vol. 397, no. 10285, 2021, pp. 1599–1601., doi:10.1016/s0140-6736(21)00712-1.
[4] REMAP-CAP Investigators. “Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.” New England Journal of Medicine, vol. 384, no. 16, 2021, pp. 1491–1502., doi:10.1056/nejmoa2100433.
[5] Salama, Carlos, et al. “Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia.” New England Journal of Medicine, vol. 384, no. 1, 2021, pp. 20–30., doi:10.1056/nejmoa2030340.
[6] Sterne, Jonathan A. C., et al. “Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19.” JAMA, vol. 324, no. 13, 2020, p. 1330., doi:10.1001/jama.2020.17023.
