ArticleFrontiers in pharmacology2020
TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 4 of them syntheses 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
41 citing papers in PubMed, 4 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Toll-like receptors polymorphisms and COVID-19: a systematic review.Molecular and cellular biochemistry · 2025Pooled it
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Safety and efficacy of toll-like receptor agonists as therapeutic agents and vaccine adjuvants for infectious diseases in animals: a systematic review.Frontiers in veterinary science · 2024Pooled it
- Adaptive immunity to SARS-CoV-2 infection: A systematic review.Frontiers in immunology · 2022Pooled it
- Sex-Specific Association of Toll-like Receptor 8 Polymorphisms with COVID-19 Case Status in a Korean Population.Life (Basel, Switzerland) · 2026Article
- Immune cell interactions and lung damage in SARS-CoV-2 special attention on monocytes/macrophages, T and B lymphocytes, dendritic cells and Toll-like receptors in SARS-CoV-2.American journal of clinical and experimental immunology · 2026Review
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
- Effects of Stems and Leaves ofGenes · 2025Article
- A Multidisciplinary and Longitudinal Framework for Enhancing Innovation Efficiency in Healthcare Systems.Journal of multidisciplinary healthcare · 2025Article
- Innate Immune Response to Viral Infection.Advances in experimental medicine and biology · 2025Review
- Clinical and Immunologic Effects of Paraprobiotics in Long-COVID Patients: A Pilot Study.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Effects of aging and lifelong aerobic exercise on expression of innate immune components in skeletal muscle of women.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- Synthesis and studies of new purines/pyrimidine derivatives as multi-targeted agents involving various receptor sites in the immune system.Molecular diversity · 2024Article
- A synbiotic mixture ofFrontiers in nutrition · 2024Article
- Impact of Toll-Like Receptor 2 and 9 Gene Polymorphisms on COVID-19: Susceptibility, Severity, and Thrombosis.Journal of inflammation research · 2023Article
- TLR agonists as vaccine adjuvants in the prevention of viral infections: an overview.Frontiers in microbiology · 2023Review
- Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients.Cells · 2022Article
- Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll-like receptors dictates pathophysiology of COVID-19 disease.Journal of medical virology · 2022Review
- Dysregulated miRNAs network in the critical COVID-19: An important clue for uncontrolled immunothrombosis/thromboinflammation.International immunopharmacology · 2022Review
- Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
By mapping the clinical pathophysiology of the novel coronavirus disease 2019 (COVID-19) against insights from virology, immunology, genomics, epidemiology and pharmacology, it is here proposed that the pathogen recognition receptor called toll like receptor 9 (TLR9) might have a pivotal role in the pathogenesis of COVID-19. Severe Acute Respiratory Syndrome Coronavirus 2, is causing the greatest global social and economic disruption since world war II. Lack of a vaccine, lack of successful treatment and limitations of the healthcare workforce and resources needed to safeguard patients with severe COVID-19 on the edge of life, demands radical preventive measures. It is urgently needed to identify biomarkers and drug candidates so that vulnerable individuals can be recognized early and severe multi-organ complications can be prevented or dampened. The TLR9 COVID-19 hypothesis describes a mechanism of action that could explain a wide spectrum of manifestations observed in patients with severe COVID-19. The introduced hypothesis proposes biomarkers for identification of vulnerable individuals and positions TLR9 as a promising multifaceted intervention target for prevention and/or treatment of COVID-19. TLR9 agonists might have value as prophylactic vaccine adjuvants and therapeutic immune stimulators at the early onset of disease. Additionally, in this current manuscript it is proposed for the first time that TLR9 could be considered as a target of "inhibition" aimed to dampen hyperinflammation and thrombotic complications in vulnerable patients that are at risk of developing late stages of COVID-19. The readily availability of TLR9 modulating drug candidates that have reached clinical testing for other disorders could favor a fast track development scenario, an important advantage under the current high unmet medical need circumstances regarding COVID-19.
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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.