What triggers a systemic storm, such as a cytokine storm?

From the Guidelines

A cytokine storm is triggered by an excessive immune response to an infection, such as COVID-19, which can lead to severe lung injury, acute respiratory distress syndrome (ARDS), and death, as seen in studies such as 1 and 1. The process begins when an initial threat, such as the SARS-CoV-2 virus, activates immune cells, which then release cytokines to coordinate the immune response.

• In a cytokine storm, this feedback loop becomes dysregulated, with each wave of cytokines triggering the release of more inflammatory molecules.
• This overwhelming inflammation can damage healthy tissues and organs, potentially leading to multi-organ failure and death.
• Risk factors include genetic predisposition, underlying health conditions, and the virulence of the infecting pathogen.
• Common triggers include severe viral infections (like influenza, SARS-CoV-2, Ebola), bacterial infections, certain medications, autoimmune disorders, and some cancer treatments like CAR T-cell therapy. Treatment typically focuses on suppressing the immune response with corticosteroids like dexamethasone, targeted immunosuppressants such as tocilizumab (which blocks IL-6), and supportive care to maintain organ function while the storm subsides, as recommended in studies such as 1 and 1.
• The use of corticosteroids, such as methylprednisolone, has been shown to be beneficial in reducing mortality and improving outcomes in patients with COVID-19, as seen in studies such as 1 and 1.
• However, the routine use of corticosteroids in viral severe acute respiratory infections, including COVID-19, is not recommended without caution, as it may have potential harms, such as delayed viral clearance and increased risk of secondary infections, as noted in studies such as 1. The most effective treatment approach is to use a combination of corticosteroids and targeted immunosuppressants, such as tocilizumab, in patients with severe COVID-19, as recommended in studies such as 1 and 1.

From the FDA Drug Label

CRS, including fatal or life-threatening reactions, occurred following treatment with TECARTUS. The incidence of CRS (first occurrence) within the first seven days after TECARTUS infusion was 83% (68/82) in patients with MCL and 90% (70/78) in patients with ALL Among patients with CRS, the key manifestations (>10%) were similar in MCL and ALL and included fever (93%), hypotension (62%), tachycardia (59%), chills (32%), hypoxia (31%), headache (21%), fatigue (20%), and nausea (13%) Serious events associated with CRS in MCL and ALL combined (≥ 2%) included hypotension, fever, hypoxia, tachycardia, and dyspnea

The trigger for a systemic storm, such as a cytokine storm, is not explicitly stated in the provided drug label. However, it is associated with the treatment with TECARTUS, and the key manifestations of CRS include fever, hypotension, tachycardia, chills, hypoxia, headache, fatigue, and nausea 2.

From the Research

Triggers of Systemic Storm

• Infection [(3,4,5,6)]
• Systemic diseases 3
• Anaphylaxis 3
• Medical interventions such as transplantation or administration of drugs 3
• Parasitic and fungal infections 4
• Autoinflammatory and autoimmune diseases 4
• Cancer 4
• Use of immunosuppressive medications 4

Types of Infections that Trigger Systemic Storm

• Viral infections such as influenza 5, SARS, and hantavirus 5
• Parasitic infections such as Histoplasma, Leishmania, Plasmodium, and Toxoplasma 4
• Fungal infections 4
• Bacterial infections such as sepsis 7

Mechanisms of Systemic Storm

• Overactivation of leukocytes driving the production and secretion of inflammatory cytokines 7
• Dysregulation of the immune response 5
• Excessive elevation of circulating cytokines 6