ArticleCell2021
Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes.
Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1,107 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Low-fielD magnEtiC Resonance Imaging of pulmonarY Parenchyma Changes Associated wiTh Confirmed SARS-CoV-2 Infection in Children and Adolescents
Low-field Magnetic Resonance Imaging to Assess Changes in Pulmonary Function Parameters in Confirmed Pediatric SARS-CoV-2 Infection
Who cites it
1,107 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,646 citations in OpenAlex.
- Advances in NLRP3 inflammasome research in viral infections: evolution, trends, and future directions.Frontiers in cellular and infection microbiology · 2026Pooled it
- T cell-associated immunity induced by heterologous recombinant BCG and purified protein vaccination confers cross-variant protection against SARS-CoV-2.Human vaccines & immunotherapeutics · 2026Article
- SARS-CoV-2-induced IgG repertoires shape T cell responses, microRNA regulation, and autoreactivity according to disease severity.Journal of translational autoimmunity · 2026Article
- Programmed cell death in inflammation: interactions and holistic perspective.Cellular & molecular immunology · 2026Review
- No time to die: cell death predicts IBD relapse.Cell research · 2026Article
- Host-pathogen interactions in tuberculosis: from immunological mechanisms to translational applications.Cell insight · 2026Review
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- PhSAN induces PANoptosis via targeting RNF25-mediated endoplasmic reticulum stress.Cell insight · 2026Article
- Intratumoral T cell activation kills tumors regardless of T cell specificity.Nature immunology · 2026Article
- MiR-342-3p Attenuates Inflammation and Pyroptosis in Severe Community-Acquired Pneumonia by Targeting EP300.Biochemical genetics · 2026Article
- Targeting iRhom2-mediated PANoptosis ameliorates acute kidney injury.Acta pharmacologica Sinica · 2026Article
- Pathogenicity Difference Between Male and Female mice by Recent SARS-CoV-2/2025.Current microbiology · 2026Article
- New visual culture of science: analysis of graphical abstracts in the life science journal "Cell".History and philosophy of the life sciences · 2026Article
- HEATR1 deficiency enhanced gastric cancer cell PANoptosis to boost anti-tumor immunity.Molecular medicine (Cambridge, Mass.) · 2026Article
- Article
- DAMPs, PAMPs, and Alarmins: From Mechanism to Therapy.MedComm · 2026Review
- IFN-α and IFN-β inhibit NLRP1-driven PANoptosis.EMBO reports · 2026Article
- DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated-Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatially organized regulated cell death-immune coupling in solid tumors: integrating spatial omics with actionable regulated cell death biology.Molecular cancer · 2026Review
- The JAK/STAT pathway: a pivotal therapeutic target in disease and advances in natural product modulation.Molecular diversity · 2026Review
1,047 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
COVID-19 is characterized by excessive production of pro-inflammatory cytokines and acute lung damage associated with patient mortality. While multiple inflammatory cytokines are produced by innate immune cells during SARS-CoV-2 infection, we found that only the combination of TNF-α and IFN-γ induced inflammatory cell death characterized by inflammatory cell death, PANoptosis. Mechanistically, TNF-α and IFN-γ co-treatment activated the JAK/STAT1/IRF1 axis, inducing nitric oxide production and driving caspase-8/FADD-mediated PANoptosis. TNF-α and IFN-γ caused a lethal cytokine shock in mice that mirrors the tissue damage and inflammation of COVID-19, and inhibiting PANoptosis protected mice from this pathology and death. Furthermore, treating with neutralizing antibodies against TNF-α and IFN-γ protected mice from mortality during SARS-CoV-2 infection, sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock. Collectively, our findings suggest that blocking the cytokine-mediated inflammatory cell death signaling pathway identified here may benefit patients with COVID-19 or other infectious and autoinflammatory diseases by limiting tissue damage/inflammation.
Indexed as
Identifiers
What OpenQuestion holds
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.