ReviewThe Lancet. Rheumatology2020
Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?
Review in The Lancet. Rheumatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Shared inflammatory pathways and therapeutic strategies in COVID-19 and cancer immunotherapy.Journal for immunotherapy of cancer · 2021Pooled it
- Population pharmacokinetic/target engagement modelling of tozorakimab in healthy volunteers and patients with chronic obstructive pulmonary disease.British journal of clinical pharmacology · 2024Trial
- Acute estradiol and progesterone therapy in hospitalized adults to reduce COVID-19 severity: a randomized control trial.Scientific reports · 2024Trial
- Eosinophil-associated intestinal immune responses following SARS-CoV-2 infection in K18-hACE2 mice.PloS one · 2026Article
- Advances in Interleukin-6 Family Cytokines and the Role in Respiratory Diseases.Journal of inflammation research · 2025Review
- Review
- IL-1 Family Blockade in Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice.PloS one · 2024Article
- A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2.ERJ open research · 2023Article
- Airway Epithelial-Derived Immune Mediators in COVID-19.Viruses · 2023Review
- The Correlation of Serum Calpain 1 Activity and Concentrations of Interleukin 33 in COVID-19 Acute Respiratory Distress Syndrome.Biomedicines · 2023Article
- Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction.Scientific reports · 2023Article
- Recombinant SARS-CoV-2 Spike Protein Stimulates Secretion of Chymase, Tryptase, and IL-1β from Human Mast Cells, Augmented by IL-33.International journal of molecular sciences · 2023Article
- Soluble ST2 as a Useful Biomarker for Predicting Clinical Outcomes in Hospitalized COVID-19 Patients.Diagnostics (Basel, Switzerland) · 2023Article
- Liquid biomarkers of macrophage dysregulation and circulating spike protein illustrate the biological heterogeneity in patients with post-acute sequelae of COVID-19.Journal of medical virology · 2023Article
- Eosinophils as potential biomarkers in respiratory viral infections.Frontiers in immunology · 2023Review
- Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery.Frontiers in immunology · 2023Article
- Article
- Plasma biomarkers associated with survival and thrombosis in hospitalized COVID-19 patients.International journal of hematology · 2022Article
- IL-33 and the Cytokine Storm in COVID-19: From a Potential Immunological Relationship towards Precision Medicine.International journal of molecular sciences · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unique cytokine signature of COVID-19 might provide clues to disease mechanisms and possible future therapies. Here, we propose a pathogenic model in which the alarmin cytokine, interleukin (IL)-33, is a key player in driving all stages of COVID-19 disease (ie, asymptomatic, mild-moderate, severe-critical, and chronic-fibrotic). In susceptible individuals, IL-33 release by damaged lower respiratory cells might induce dysregulated GATA-binding factor 3-expressing regulatory T cells, thereby breaking immune tolerance and eliciting severe acute respiratory syndrome coronavirus 2-induced autoinflammatory lung disease. Such disease might be initially sustained by IL-33-differentiated type-2 innate lymphoid cells and locally expanded γδ T cells. In severe COVID-19 cases, the IL-33-ST2 axis might act to expand the number of pathogenic granulocyte-macrophage colony-stimulating factor-expressing T cells, dampen antiviral interferon responses, elicit hyperinflammation, and favour thromboses. In patients who survive severe COVID-19, IL-33 might drive pulmonary fibrosis by inducing myofibroblasts and epithelial-mesenchymal transition. We discuss the therapeutic implications of these hypothetical pathways, including use of therapies that target IL-33 (eg, anti-ST2), T helper 17-like γδ T cells, immune cell homing, and cytokine balance.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.