Cytokine release syndrome

Summary

Cytokine release syndrome (MONDO:0600008) is a disease and 91 clinical trials. Top therapeutic interventions include anakinra, fluoxetine, and methylene blue cation. A subtype of immune system disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Clinical trials: 91

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cytokine release syndrome
Mondo ID	MONDO:0600008
MeSH	D000080424
ICD-10-CM	D89.83
NCIT	C78251
UMLS	C0948245
MedGen	215297
Is cancer (heuristic)	no

Also known as: CRS · cytokine storm · cytokine-associated toxicity

Disease family

This is a subtype of immune system disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › immune system disorder › cytokine release syndrome

Related subtypes (46): hypersensitivity reaction disease, immune system cancer, immune system organ benign neoplasm, bone marrow disorder, thymus gland disorder, inborn error of immunity, leukocyte disorder, psoriasis, spondyloarthropathy, aggressive insulitis, benign insulitis, inflammatory bowel disease, autoimmune disease, TNF receptor 1-associated periodic fever syndrome, epidermodysplasia verruciformis, Vici syndrome, proteosome-associated autoinflammatory syndrome, hyperimmunoglobulinemia D with periodic fever, transcobalamin II deficiency, pyogenic arthritis-pyoderma gangrenosum-acne syndrome, granulomatosis with polyangiitis, autosomal recessive osteopetrosis 7, graft versus host disease, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, Roifman syndrome, cryopyrin-associated periodic syndrome, anti-HLA hyperimmunization, acquired immunodeficiency, erythroderma desquamativum, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, familial Mediterranean fever, 22q11.2 deletion syndrome, T-cell large granular lymphocyte leukemia, twin to twin transfusion syndrome, immunodeficiency disease, immunoproliferative disorder, cytokine receptor deficiency, immunodeficiency-related disorder, phagocytic cell dysfunction, thrombocytopenic purpura, lymphoid system disorder, immune reconstitution inflammatory syndrome, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, early-onset autoimmunity-autoinflammation-immunodeficiency syndrome, CADINS disease, autoinflammation, panniculitis, and dermatosis syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Tocilizumab	Approved (phase 4)

Clinical trials & evidence

Clinical trials

Clinical trials: 91.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	49
PHASE2	22
PHASE1/PHASE2	6
PHASE3	5
PHASE4	4
PHASE1	3
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04377308	PHASE4	COMPLETED	Fluoxetine to Reduce Intubation and Death After COVID19 Infection
NCT05133635	PHASE4	WITHDRAWN	High-Dose Corticosteroid or Tocilizumab for Clinical Worsening of COVID-19
NCT05474924	PHASE4	UNKNOWN	The Role of Budesonide Intrapolyp Injection in CRSwNP
NCT05491304	PHASE4	UNKNOWN	Cytokine Guided Risk Stratification and Treatment in Pediatric Hemophagocytic Lymphohistiocytosis
NCT04327505	PHASE2/PHASE3	TERMINATED	Safety and Efficacy of Hyperbaric Oxygen for ARDS in Patients With COVID-19
NCT04362111	PHASE3	COMPLETED	Early Treatment of Cytokine Storm Syndrome in Covid-19
NCT04362137	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm
NCT04403685	PHASE3	TERMINATED	Safety and Efficacy of Tocilizumab in Moderate to Severe COVID-19 With Inflammatory Markers
NCT04643678	PHASE2/PHASE3	COMPLETED	Anakinra in the Management of COVID-19 Infection
NCT04979884	PHASE3	COMPLETED	Safety and Effectiveness of Cyclosporin in the Management of COVID19 ARDS Patients in Alexandria University Hospital
NCT05096052	PHASE3	UNKNOWN	PROlectin M, a Nucleocapsid TErminal GaleCTin Antagonist for COVID-19
NCT04975555	PHASE2	ACTIVE_NOT_RECRUITING	Study to Evaluate the Role of Siltuximab in Treatment of Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) Related to CAR-T Cell Therapy
NCT05611710	PHASE2	ACTIVE_NOT_RECRUITING	Anakinra in Dengue With Hyperinflammation ( AnaDen )
NCT05905328	PHASE1/PHASE2	RECRUITING	Study of CTO1681 for the Prevention and Treatment of CRS in DLBCL Patients Receiving CAR T-Cell Therapy
NCT06308926	PHASE2	NOT_YET_RECRUITING	MRG-001 as an Immunoregulatory and Regenerative Therapy for ARDS Patients
NCT06703216	PHASE1/PHASE2	NOT_YET_RECRUITING	Pre-emptive Anakinra for Cytokine Event Reduction
NCT03533101	PHASE1/PHASE2	COMPLETED	Tocilizumab for Cytokine Release Syndrome Prophylaxis in Haploidentical Transplantation
NCT04071366	PHASE2	COMPLETED	A Study of Itacitinib for the Prevention of Cytokine Release Syndrome Induced by Immune Effector Cell Therapy
NCT04150913	PHASE2	COMPLETED	A Phase 2 Trial of Anakinra for the Prevention of CAR-T Cell Mediated Neurotoxicity
NCT04366908	PHASE2	COMPLETED	Prevention and Treatment With Calcifediol of COVID-19 Induced Acute Respiratory Syndrome
NCT04374149	PHASE2	COMPLETED	Therapeutic Plasma Exchange Alone or in Combination With Ruxolitinib in COVID-19 Associated CRS
NCT04377503	PHASE2	TERMINATED	Tocilizumab Versus Methylprednisolone in the Cytokine Release Syndrome of Patients With COVID-19
NCT04378244	PHASE1/PHASE2	WITHDRAWN	CORONA: A Study Using DeltaRex-G Gene Therapy for Symptomatic COVID-19
NCT04415073	PHASE2	TERMINATED	A Phase 2 Study to Evaluate Axatilimab for Hospitalized Participants With Respiratory Involvement Secondary to COVID-19
NCT04433078	PHASE2	WITHDRAWN	RepurpoSing Old Drugs TO SuppRess a Modern Threat: COVID-19 STORM
NCT04433546	PHASE2	TERMINATED	Pemziviptadil (PB1046), a Long-acting, Sustained Release Human VIP Analogue, Intended to Provide Clinical Improvement to Hospitalized COVID-19 Patients at High Risk for Rapid Clinical Deterioration and Acute Respiratory Distress Syndrome (ARDS).
NCT04475588	PHASE2	COMPLETED	Efficacy and Safety of Itolizumab in COVID-19 Complications
NCT04517162	PHASE1/PHASE2	UNKNOWN	Intramuscular Effect of Polymerized Type I Collagen on the Cytokine Storm in COVID-19 Patients
NCT04540120	PHASE2	TERMINATED	Safety and Efficacy of Dapansutrile for Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome
NCT04603742	PHASE2	WITHDRAWN	Anakinra, COVID-19, Cytokine Storm
NCT04753476	PHASE2	UNKNOWN	Treatment of Severe COVID-19 Patients Using Secretome of Hypoxia-Mesenchymal Stem Cells in Indonesia
NCT04781803	PHASE2	UNKNOWN	Cyclosporine on Day Zero as Prophylaxis for Cytokine Release Syndrome
NCT05013034	PHASE2	UNKNOWN	Exploratory Regimen of Basiliximab for Treatment of Pulmonary Cytokine Storm in SARS-CoV-2 Hospitalized Adult Patients
NCT05018975	PHASE2	WITHDRAWN	Tazemetostat for the Treatment of Moderate to Severe COVID-19 Infection
NCT05019287	PHASE1/PHASE2	COMPLETED	Menstrual Blood Stem Cells in Severe Covid-19
NCT05349669	PHASE2	COMPLETED	Jafron Haemoadsorption During Cardiopulmonary Bypass
NCT06003972	PHASE2	COMPLETED	Asses the Anti-inflammatory Effects of Short Term Copaxone Therapy on Patients the Acute Decompensated Heart Failure
NCT06352866	PHASE2	WITHDRAWN	Siltuximab for Cytokine Release Syndrome Prophylaxis Prior to tx w/ Teclistamab in RRMM
NCT06390748	PHASE2	COMPLETED	Esmolol in Sepsis Management:Evaluating Immunomodulatory Effects and Impact on Patient Outcomes
NCT06447376	PHASE1	RECRUITING	Study of Cytokine Release Syndrome Prophylaxis and Treatment With Siltuximab Prior to Epcoritamab

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ANAKINRA	4	4
FLUOXETINE	4	3
METHYLENE BLUE CATION	4	3
SILTUXIMAB	4	3
AXICABTAGENE CILOLEUCEL	4	2
CALCIFEDIOL ANHYDROUS	4	2
RUXOLITINIB	4	2
AXATILIMAB	4	1
BASILIXIMAB	4	1
EPCORITAMAB	4	1
ESMOLOL	4	1
ETOPOSIDE	4	1
GLATIRAMER ACETATE	4	1
INFLIXIMAB	4	1
METHYLPREDNISOLONE	4	1
METHYLPREDNISOLONE SODIUM SUCCINATE	4	1
OXYGEN	4	1
PIPERACILLIN	4	1
REMDESIVIR	4	1
TAZEMETOSTAT	4	1
TAZOBACTAM	4	1
TOCILIZUMAB	4	1
ITACITINIB	3	1
DAPANSUTRILE	2	1
CHEMBL5220618	0	4
CHEMBL4637163	0	2
CHEMBL5398431	0	1
CHEMBL4061258	0	1
CHEMBL5094495	0	1
CHEMBL5280654	0	1