Cytokine storm syndrome (CSS) is a serious complication of inflammatory immune diseases or the treatment of malignancies; It can also appear during the progression of COVID-19. CSS is caused by dysregulation of cytokine synthesis, including pro-inflammatory, regulatory, and anti-inflammatory cytokines and chemokines, leading to pathological activation of innate and adaptive immunity (mediated by Th1 and Th17). Interleukin-6 (IL-6) plays an important role in the pathogenesis of CSS. The significant role of IL-6 in the pathogenesis of interleukins COVID-19 was confirmed in a variety of studies, which showed that the plasma concentration of IL-6 was increased in patients with severe COVID-19.
Currently, IL-6 inhibitory therapies are not yet approved for the treatment of COVID-19; however, these drugs, including tocilizumab (TCZ), are used off-label for the treatment of patients with severe COVID-19, including life-threatening conditions. The role of IL-6 in the pathogenesis of CSS during COVID-19 is important, however, a number of related issues are still unclear. These issues include indications for treatment with IL-6 inhibitors, as well as estimating the risk associated with the disease, outcomes, treatment options, and adverse drug reactions.
The development of personalized immunomodulatory therapy, regarding the role of cytokines in pathogenesis, requires studies that aimed to find other relevant therapeutic targets for the treatment of CSS in patients with COVID-19. These therapeutic targets include the inhibition of IL-1, IL-6, TNFα, GM-CSF, IFNγ, IL-17, IL-18 and also the activation of the complement system.
The challenge of CSS in COVID-19 patients is to identify the correct scientific targets and develop clinical trials aimed at evaluating pathogenesis and treating immune-mediated inflammatory diseases (IMID). Hopefully, the significant efforts of scientists and clinicians around the world will improve the prognosis of COVID-19 patients and provide useful information on the IMIDs needed to support the fight for the treatment of potential viral outbreaks and the treatment of known IMIDs.
The role of interleukin 6 inhibitors in the therapy of severe COVID-19 Nassonov E, Samsonov M.
MRI, resident macrophages; INF, interferons; NK, natural killers; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor, TNFα, tumor necrosis factor-alpha; IP-10, protein 10 induced by interferon (IFN) γ; MIP1α, macrophage inflammatory protein; CCL2, CCL7, CXCL9, CXCL10, chemokines.