ArticleJCI insight2024
Prolonged exposure to lung-derived cytokines is associated with activation of microglia in patients with COVID-19.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Five-decade prevalence of delirium in pneumonia, risk factors and associated mortality: a systematic review and meta-analysis.European respiratory review : an official journal of the European Respiratory Society · 2025Pooled it
- The CRAC channel inhibitor Auxora reprograms pathogenic alveolar macrophage-T cell circuits in viral pneumonia.The Journal of clinical investigation · 2026Article
- Functional immune changes are conserved in COVID-19 and trauma patients receiving intensive care.Nature communications · 2026Article
- Longitudinal analysis reveals myeloid cell contributions to murine neuroPASC pathogenesis.Nature communications · 2026Article
- Translational insights into Long-COVID: evaluation of preclinical animal models along the lung-brain-immune axis with focus on Golden Syrian Hamsters.Journal of neuroinflammation · 2026Review
- Pathogen-specific host responses define distinct pneumonia endotypes in the human lung.bioRxiv : the preprint server for biology · 2026Article
- When Viruses Talk through Extracellular Vesicles: a New Perspective on Sars-Cov-2-Induced Neurodegeneration.Journal of extracellular vesicles · 2026Article
- Intranasal Anti-CD3 Antibody Treatment Attenuates Post-COVID Neuroinflammation and Enhances Hippocampal Neurogenesis and Cognitive Function in Mice.bioRxiv : the preprint server for biology · 2026Article
- Barrier breakdown: lung-brain crosstalk in systemic inflammation.Journal of neuroinflammation · 2026Review
- Influenza A infection accelerates disease-associated microglia formation during physiological aging.bioRxiv : the preprint server for biology · 2025Article
- Multi-omics profiling in severe pneumonia: the importance of robust study design.The European respiratory journal · 2025Article
- The LPAR1 antagonist, PIPE-791 produces antifibrotic effects in models of lung fibrosis.Respiratory research · 2025Article
- Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [Brain, behavior, & immunity - health · 2025Article
- Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health.GeroScience · 2025Review
- Detrimental Effects of Anti-Nucleocapsid Antibodies in SARS-CoV-2 Infection, Reinfection, and the Post-Acute Sequelae of COVID-19.Pathogens (Basel, Switzerland) · 2024Review
- SARS-CoV-2 infection in microglia and its sequelae: What do we know so far?Brain, behavior, & immunity - health · 2024Review
- Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19.Nature immunology · 2024Article
- Distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia.Nature immunology · 2024Article
- Uncovering the Contrasts and Connections in PASC: Viral Load and Cytokine Signatures in Acute COVID-19 versus Post-Acute Sequelae of SARS-CoV-2 (PASC).Biomedicines · 2024Review
- MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID.medRxiv : the preprint server for health sciences · 2024Article
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUNDSurvivors of pneumonia, including SARS-CoV-2 pneumonia, are at increased risk for cognitive dysfunction and dementia. In rodent models, cognitive dysfunction following pneumonia has been linked to the systemic release of lung-derived pro-inflammatory cytokines. Microglia are poised to respond to inflammatory signals from the circulation, and their dysfunction has been linked to cognitive impairment in murine models of dementia and in humans.METHODSWe measured levels of 55 cytokines and chemokines in bronchoalveolar lavage fluid and plasma from 341 patients with respiratory failure and 13 healthy controls, including 93 unvaccinated patients with COVID-19 and 203 patients with other causes of pneumonia. We used flow cytometry to sort neuroimmune cells from postmortem brain tissue from 5 patients who died from COVID-19 and 3 patients who died from other causes for single-cell RNA-sequencing.RESULTSMicroglia from patients with COVID-19 exhibited a transcriptomic signature suggestive of their activation by circulating pro-inflammatory cytokines. Peak levels of pro-inflammatory cytokines were similar in patients with pneumonia irrespective of etiology, but cumulative cytokine exposure was higher in patients with COVID-19. Treatment with corticosteroids reduced expression of COVID-19-specific cytokines.CONCLUSIONProlonged lung inflammation results in sustained elevations in circulating cytokines in patients with SARS-CoV-2 pneumonia compared with those with pneumonia secondary to other pathogens. Microglia from patients with COVID-19 exhibit transcriptional responses to inflammatory cytokines. These findings support data from rodent models causally linking systemic inflammation with cognitive dysfunction in pneumonia and support further investigation into the role of microglia in pneumonia-related cognitive dysfunction.FUNDINGSCRIPT U19AI135964, UL1TR001422, P01AG049665, P01HL154998, R01HL149883, R01LM013337, R01HL153122, R01HL147290, R01HL147575, R01HL158139, R01ES034350, R01ES027574, I01CX001777, U01TR003528, R21AG075423, T32AG020506, F31AG071225, T32HL076139.
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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.