ArticleJCI insight2021
IL-13 is a driver of COVID-19 severity.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Immunoinflammatory evidence of rheumatoid arthritis caused by COVID-19.Biological research · 2025Pooled it
- Assessing the Potential of an Enzymatically Liberated Salmon Oil to Support Immune Health Recovery from Acute SARS-CoV-2 Infection via Change in the Expression of Cytokine, Chemokine and Interferon-Related Genes.International journal of molecular sciences · 2024Trial
- Pulmonary Function and Survival 1 Year After Dupilumab Treatment of Acute Moderate to Severe Coronavirus Disease 2019: A Follow-up Study From a Phase 2a Trial.Open forum infectious diseases · 2024Trial
- A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings.Frontiers in immunology · 2024Trial
- Oral hymecromone decreases hyaluronan in human study participants.The Journal of clinical investigation · 2022Trial
- Antibody repertoire associated with clinically diverse presentations of pediatric SARS-CoV-2 infection.Scientific reports · 2026Article
- Coordinated immune-epithelial dynamics in the nasal epithelium protect against respiratory virus infection.bioRxiv : the preprint server for biology · 2026Article
- Autoantibodies to IL-1Ra and PGRN in severe COVID-19 are associated with inflammation-induced hyperphosphorylated antigen isoforms.Nature communications · 2026Article
- The hyaluronan receptor CD44 drives COVID-19 severity through its regulation of neutrophil migration.PLoS pathogens · 2026Article
- Prospective multicentre study of upper respiratory mucosal transcriptomics reveals two major endotypes of critically ill COVID-19 patients.Communications medicine · 2026Article
- Real-world immune dynamics following COVID-19 vaccination and breakthrough infection: a paired-sample study in Zhejiang Province, China.Frontiers in immunology · 2026Article
- CXCR3 ameliorates neutrophil-dependent disease severity in SARS-CoV-2 infection by regulating CD4Frontiers in immunology · 2026Article
- Integrated humoral and inflammatory signatures predict outcomes in severe COVID-19: a 14-day longitudinal analysis.Clinical & translational immunology · 2026Article
- Principal component analysis of cytokine signature in COVID-19 and Long COVID.Frontiers in immunology · 2026Article
- Hyaluronan Ameliorates Viral Pneumonia in Mice and Humans by Inhibiting Transcription Factor E2F1.American journal of respiratory cell and molecular biology · 2026Article
- IL-10- and IL-13-Biased T Cell Responses to SARS-CoV-2 Vaccination in Diabetes.European journal of immunology · 2025Article
- The hyaluronan receptor CD44 drives COVID-19 severity through its regulation of neutrophil migration.bioRxiv : the preprint server for biology · 2025Article
- Immunological Mechanisms Underlying Allergy Predisposition After SARS-CoV-2 Infection in Children.Cells · 2025Review
- Redefining Normal: Cytokine Dysregulation in Long COVID and the Post-Pandemic Healthy Donors.International journal of molecular sciences · 2025Article
- IL-4 and TGF-β regulate inflammatory cytokines and cellular infiltration in the lung and systemic IL-6 in mouse-adapted SARS-CoV-2 infection.ImmunoHorizons · 2025Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 8 institutions in 4 countries.
Funding
Abstract
Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2-infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti-IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13-induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13-mediated HA synthesis in pulmonary pathology.
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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.