ArticleScience immunology2021
SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation.
Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
138 citing papers in PubMed, 1 synthesis or guideline pooled it, 200 citations in OpenAlex.
- JAK inhibitors and COVID-19.Journal for immunotherapy of cancer · 2022Pooled it
- Efficacy and Safety of Tofacitinib in Patients with Polymyalgia Rheumatica (EAST PMR): An open-label randomized controlled trial.PLoS medicine · 2023Trial
- Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial.Respiratory research · 2022Trial
- Collectin-11, a complement pattern recognition molecule, mediates pulmonary SARS-CoV-2 neutralization and protection.PLoS pathogens · 2026Article
- Associations between respiratory diseases and lung cancer risk: a secondary analysis of the large-scale prospective UK biobank cohort.BMJ open respiratory research · 2026Article
- C/EBP-β-regulated complement hyperactivation in spleen of SFTSV-infected mice: A clue to targeted complement therapy.PLoS pathogens · 2026Article
- SARS-CoV-2 infection in brain tumors and the association with alterations in the tumor immune microenvironment.Cancer biology & medicine · 2026Article
- Mucosally sourced complement factor B modulates the host response to colitis.bioRxiv : the preprint server for biology · 2026Article
- A new perspective on the pathophysiology of kidney diseases: the intracellular complement system- "complosome".Frontiers in nephrology · 2026Review
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model.Virulence · 2025Article
- Article
- Impact of complement system proteins on the clinical progression of hospitalized patients with COVID-19.BMC infectious diseases · 2025Article
- Emerging roles for complement in lung transplantation.The Journal of clinical investigation · 2025Review
- Unveiling Moxibustion's Impact on AD Mice Learning and Memory: Role of Mitochondrial Respiratory Chain Complex I Subunit in the Hippocampus.Molecular neurobiology · 2025Article
- The role of complement in long COVID pathogenesis.JCI insight · 2025Review
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Inside job: Roles of intracellular C3.The Journal of allergy and clinical immunology · 2025Review
- Article
- Complement Activation is More Pronounced in the Kidneys of Critically Ill Patients With COVID-19 Than in Those With Bacterial Sepsis.Kidney international reports · 2025Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 12 institutions in 4 countries.
Funding
Abstract
Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells. Infection of respiratory epithelial cells with SARS-CoV-2 generated activated complement component C3a and could be blocked by a cell-permeable inhibitor of complement factor B (CFBi), indicating the presence of an inducible cell-intrinsic C3 convertase in respiratory epithelial cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Genes induced by SARS-CoV-2 and the drugs that could normalize these genes both implicated the interferon-JAK1/2-STAT1 signaling system and NF-κB as the main drivers of their expression. Ruxolitinib, a JAK1/2 inhibitor, normalized interferon signature genes and all complement gene transcripts induced by SARS-CoV-2 in lung epithelial cell lines, but did not affect NF-κB-regulated genes. Ruxolitinib, alone or in combination with the antiviral remdesivir, inhibited C3a protein produced by infected cells. Together, we postulate that combination therapy with JAK inhibitors and drugs that normalize NF-κB-signaling could potentially have clinical application for severe COVID-19.
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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.