Cytokine release syndrome (CRS) is an overwhelming and potentially life-threatening inflammatory response often seen in oncology care, most commonly with monoclonal antibodies and CAR T-cell therapies. It may also be triggered by an infection or develop following infusion of agents targeting the immune system.

Presentation and Recognition

CRS’s pathophysiology is not fully understood. Activation of the immune system engages lymphocytes (T cells, B cells, and natural killer cells) and myeloid cells (dendritic cells, monocytes, and macrophages). Immune and nonimmune cells release interferons, interleukins, and other inflammatory cytokines, triggering a cascade of events that leads to a generalized inflammatory response.

Initial presentation includes mild flu-like symptoms of fever, arthralgias, headache, and fatigue. Patients at risk should be monitored closely for vital sign or neurologic changes that can occur as CRS progresses quickly to an overwhelming systemic reaction involving capillary leak syndrome, hypotension, disseminated intravascular coagulation, and multiple organ failure. Inflammation leads to hyperpermeability of capillaries, shifting fluid into third spaces such as the lungs and interstitial tissues.

Laboratory findings include a slow rise in ferritin, a rapid rise in C-reactive protein, increased creatinine, and elevated liver enzymes, including lactate dehydrogenase level.

How It Affects Patients With COVID-19

CRS may occur in patients with bacterial or viral infections and has become increasingly prevalent in COVID-19. The inflammatory storm and subsequent immunopathologic changes follow the same pathology, affecting the lungs and leading to acute respiratory distress syndrome, the leading cause of death in patients with COVID-19. As with CRS in the oncology setting, the cytokine storm seen in COVID-19 patients can involve multiple organ systems, including hypotension, respiratory failure, coagulopathies, cardiac dysfunction, and renal and liver failure.

Treatment and Management

Supportive care is essential to maintain stability, including possible transfer to the intensive care unit. Treatment with antipyretics, antiemetics, oxygen, hemodynamic monitoring, and vasopressor support may be needed to prevent multisystem organ failure.

Tocilizumab has become the medication of choice for CRS. A humanized monoclonal antibody targeting the IL-6 receptor, the drug prevents inflammation by blocking the binding of IL-6 and has been found to be effective in both oncology and COVID-19 settings. Clinical indications for treatment include worsening respiratory status or uncontrolled hypotension.

Nurses are instrumental in early recognition and treatment of CRS. Awareness of the risk factors and prompt assessment and management offer patients a better chance of recovery.