Evidence map›Paper›PMID 34339626›Full record

ReviewThe Lancet. Neurology2021

Post-viral effects of COVID-19 in the olfactory system and their implications.

Michael S Xydakis, Mark W Albers, Eric H Holbrook, Dina M Lyon, Robert Y Shih, Johannes A Frasnelli, Axel Pagenstecher, Alexandra Kupke, Lynn W Enquist, Stanley Perlman

Open access · bronzeAbstract readReview
In one paragraph

Review in The Lancet. Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 4 pooled it
19.7field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

107 citing papers in PubMed, 4 syntheses or guidelines pooled it, 184 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024
    Trial
  6. Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023
    Trial
  7. Trial
  8. Cognitive assessment of patients with post-COVID olfactory dysfunction and impaired domains.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  9. Review
  10. Therapeutic Effects and Mechanisms of Olfactory Training in a Murine Model of Olfactory Dysfunction.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026
    Article
  11. Effect of intranasal vitamin A nanoparticles on persistent olfactory dysfunction: a randomized clinical trial.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
    Article
  12. Article
  13. Article
  14. Review
  15. Combination antiviral and anti-inflammatory therapy mitigates persistent neurological deficits in mice post SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. IFN-bioRxiv : the preprint server for biology · 2025
    Article

47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 8 institutions in 3 countries.

Michael S XydakisHuman Performance Wing, Air Force Research Lab, US Department of Defense, Wright-Patterson Air Force Base, Dayton, OH, USA. Electronic address: michael.xydakis@gmail.com.
Mark W AlbersMassachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Eric H HolbrookMassachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
Dina M LyonHuman Performance Wing, Air Force Research Lab, US Department of Defense, Wright-Patterson Air Force Base, Dayton, OH, USA.
Robert Y ShihDivision of Neuroradiology, Walter Reed National Military Medical Center, US Department of Defense, Bethesda, MD, USA.
Johannes A FrasnelliDepartment of Anatomy, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada.
Axel PagenstecherDepartment of Neuropathology, Philipps University of Marburg, Marburg, Germany.
Alexandra KupkeMarburg Virology Institute, Philipps University of Marburg, Marburg, Germany.
Lynn W EnquistPrinceton Neuroscience Institute, Princeton University, Princeton, NJ, USA.
Stanley PerlmanDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Philipps University of Marburg · DEWright-Patterson Air Force Base · USMassachusetts Eye and Ear Infirmary · USMassachusetts General Hospital · USPrinceton University · USUniversité du Québec à Trois-Rivières · CAUniversity of Iowa · USWalter Reed National Military Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after viral infection, which provides a research opportunity to evaluate the natural course of this neurological finding. Clinical trials and prospective and histological studies of new-onset post-viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples. Although data from neuropathological specimens are now available, neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge. RECENT DEVELOPMENTS: The active replication of SARS-CoV-2 within the brain parenchyma (ie, in neurons and glia) has not been proven. Nevertheless, post-viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID-19. Evidence is also sparse for a direct causal relation between SARS-CoV-2 infection and abnormal brain findings at autopsy, and for trans-synaptic spread of the virus from the olfactory epithelium to the olfactory bulb. Taken together, clinical, radiological, histological, ultrastructural, and molecular data implicate inflammation, with or without infection, in either the olfactory epithelium, the olfactory bulb, or both. This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has revealed localised inflammation in intracranial olfactory structures. To date, histopathological, ultrastructural, and molecular evidence does not suggest that SARS-CoV-2 is an obligate neuropathogen. WHERE NEXT?: The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate that, in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term. An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease. Persistent olfactory impairment with or without perceptual distortions (ie, parosmias or phantosmias) after SARS-CoV-2 infection could, therefore, serve as a marker to identify people with an increased long-term risk of neurological disease.

Indexed as

BrainCOVID-19HumansNeurodegenerative DiseasesOlfaction DisordersOlfactory MucosaProspective StudiesSmell

Identifiers

PMID34339626
PMCPMC8324113
OpenAlexW3191883126

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.