ArticleiScience2023
SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Post-COVID-19 Vaccination Meningitis and Meningoencephalitis: A Systematic Review of Case Series and Case Reports.The American journal of tropical medicine and hygiene · 2025Pooled it
- Donepezil for Fatigue and Psychological Symptoms in Post-COVID-19 Condition: A Randomized Clinical Trial.JAMA network open · 2025Trial
- Review
- Donepezil ameliorates fatigue and depression in PASC patients with HHV-6B SITH-1-induced acetylcholine deficiency.Frontiers in pharmacology · 2026Article
- Integrative perspectives on electroacupuncture modulation of vagal-cholinergic and neuro-immune-metabolic regulation in long COVID.Frontiers in integrative neuroscience · 2026Review
- Review
- Review
- Spatial transcriptomics of the epipharynx in long COVID identifies SARS-CoV-2 signalling pathways and the therapeutic potential of epipharyngeal abrasive therapy.Scientific reports · 2025Article
- Efficacy of Donepezil for Fatigue and Psychological Symptoms in Post-COVID-19 Condition: Study Protocol for a Multicenter Randomized, Placebo-controlled, Double-blind Trial.Annals of clinical epidemiology · 2024Article
- Quality of Sleep and Mental Symptoms Contribute to Health-Related Quality of Life after COVID-19 Pneumonia, a Follow-Up Study of More than 2 Years.Biomedicines · 2024Article
- Multifaceted role of SARS-CoV-2 structural proteins in lung injury.Frontiers in immunology · 2024Review
- Long COVID, the Brain, Nerves, and Cognitive Function.Neurology international · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurological complications that occur in SARS-CoV-2 infection, such as olfactory dysfunction, brain inflammation, malaise, and depressive symptoms, are thought to contribute to long COVID. However, in autopsies of patients who have died from COVID-19, there is normally no direct evidence that central nervous system damage is due to proliferation of SARS-CoV-2. For this reason, many aspects of the pathogenesis mechanisms of such symptoms remain unknown. Expressing SARS-CoV-2 S1 protein in the nasal cavity of mice was associated with increased apoptosis of the olfactory system and decreased intracerebral acetylcholine production. The decrease in acetylcholine production was associated with brain inflammation, malaise, depressive clinical signs, and decreased expression of the cytokine degrading factor ZFP36. Administering the cholinesterase inhibitor donepezil to the mice improved brain inflammation, malaise and depressive clinical signs. These findings could contribute to the elucidation of the pathogenesis mechanisms of neurological complications associated with COVID-19 and long COVID.
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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.