ReviewActa neuropathologica2021
The olfactory nerve is not a likely route to brain infection in COVID-19: a critical review of data from humans and animal models.
Review in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- The D614G Virus Mutation Enhances Anosmia in COVID-19 Patients: Evidence from a Systematic Review and Meta-analysis of Studies from South Asia.ACS chemical neuroscience · 2021Pooled it
- Self-reported symptom study of COVID-19 chemosensory dysfunction in Malaysia.Scientific reports · 2022Trial
- The Unmet Need of Olfactory Testing in Inflammatory Disorders of the Upper Airways-An EAACI Position Paper.Allergy · 2026Review
- Olfactory immunity: defending the neural-mucosal barrier.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Review
- Clinical translation of salivary MicroAge for understanding the oral-systemic connection in healthy longevity.Frontiers in microbiology · 2026Review
- SARS-CoV-2-induced damage to rat cortical neuronal networks ex vivo is mediated by the pro-inflammatory activation of the cGAS-STING pathway.Journal of neurovirology · 2025Article
- Viral destruction of the olfactory mucosa elicits immune residence, bone metaplasia, and long-term smell loss.Mucosal immunology · 2025Article
- Mapping the Olfactory Brain: A Systematic Review of Structural and Functional Magnetic Resonance Imaging Changes Following COVID-19 Smell Loss.Brain sciences · 2025Review
- Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19.Nature neuroscience · 2025Article
- Acute and long-term effects of COVID-19 on brain and mental health: A narrative review.Brain, behavior, and immunity · 2025Review
- Role of toll-like receptors in post-COVID-19 associated neurodegenerative disorders?Frontiers in medicine · 2025Review
- Receptors Involved in COVID-19-Related Anosmia: An Update on the Pathophysiology and the Mechanistic Aspects.International journal of molecular sciences · 2024Review
- A systematic scoping review of the neurological effects of COVID-19.Neurotoxicology · 2024Article
- Long COVID: From olfactory dysfunctions to viral Parkinsonism.World journal of otorhinolaryngology - head and neck surgery · 2024Article
- Article
- Histochemical Evidence for Reduced Immune Response in Nasal Mucosa of Patients with COVID-19.International journal of molecular sciences · 2024Article
- SARS-CoV-2 and Other Respiratory Viruses in Human Olfactory Pathophysiology.Microorganisms · 2024Review
- Brain Pathology in COVID-19: Clinical Manifestations and Potential Mechanisms.Neuroscience bulletin · 2024Review
- COVID-19 and the brain: understanding the pathogenesis and consequences of neurological damage.Molecular biology reports · 2024Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
One of the most frequent symptoms of COVID-19 is the loss of smell and taste. Based on the lack of expression of the virus entry proteins in olfactory receptor neurons, it was originally assumed that the new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) does not infect olfactory neurons. Recent studies have reported otherwise, opening the possibility that the virus can directly infect the brain by traveling along the olfactory nerve. Multiple animal models have been employed to assess mechanisms and routes of brain infection of SARS-CoV-2, often with conflicting results. We here review the current evidence for an olfactory route to brain infection and conclude that the case for infection of olfactory neurons is weak, based on animal and human studies. Consistent brain infection after SARS-CoV-2 inoculation in mouse models is only seen when the virus entry proteins are expressed abnormally, and the timeline and progression of rare neuro-invasion in these and in other animal models points to alternative routes to the brain, other than along the olfactory projections. COVID-19 patients can be assured that loss of smell does not necessarily mean that the SARS-CoV-2 virus has gained access to and has infected their brains.
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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.