JNN Journal of Neuromonitoring & NeurophysiologyJ Neuromonit Neurophysiol 2799-5496 3058-5449 Korean Intraoperative Neural Monitoring Society 10.54441/jnn.2025.5.2.152 jnn-2025-5-2-152 Review Article Neurophysiological mechanisms of anosmia: shared pathways in traumatic brain injury, chronic rhinosinusitis, COVID-19, and neurodegenerative disease http://orcid.org/0000-0002-8693-8352 VenturaReiza 1 http://orcid.org/0000-0003-1331-364X MoJi-Hun 1 2 Beckman Laser Institute Korea, Cheonan, Republic of Korea Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Republic of Korea Corresponding to Ji-Hun Mo E-mail. jihunmo@gmail.com 11 2025 30 11 2025 5 2 152 159 21 05 2025 9 06 2025 13 06 2025 Copyright © 2025 Korean Intraoperative Neural Monitoring Society 2025 Articles published in the JNN are open-access, distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Anosmia, the loss or alteration of the sense of smell, is a condition with multifactorial causes and consequences for patient safety, nutrition, and mental health. This review explores the neurophysiological mechanisms underlying anosmia, focusing on both peripheral and central components of olfactory dysfunction. In traumatic brain injury, anosmia occurs due to direct mechanical damage to the olfactory nerve fibers or olfactory bulb, with experimental models revealing sustained inflammation, microglial activation, and oxidative stress that disrupt olfactory signaling. Chronic rhinosinusitis-induced anosmia, attributed to mechanical obstruction, and inflammatory changes within the olfactory mucosa that impair neurogenesis and sensory function. COVID-19-related anosmia is prevalent and involves multiple mechanisms: local epithelial inflammation due to angiotensin-converting enzyme 2 receptor-mediated viral entry, damage to sustentacular cells, disruption of olfactory cilia, cytokine release, and olfactory bulb. These diverse etiologies share overlapping pathological features including neuroinflammation, impaired neuronal regeneration, and altered olfactory processing. Anosmia is not only a symptom but may also serve as an early biomarker of neurological decline, particularly in neurodegenerative disorders. Accurate diagnosis requires objective olfactory testing, and management may include pharmacological, rehabilitative, and supportive strategies. Understanding the shared neurophysiological underpinnings of anosmia can enhance early detection of systemic disease and guide targeted therapeutic interventions.

 Anosmia Olfactory dysfunction COVID-19 Chronic rhinosinusitis Neurodegenerative diseases Introduction

Anosmia, the loss or change in the sense of smell [1], is a significant health issue with various causes and considerable impact on patients’ lives. It is a well-established consequence of head injury [2], affecting a substantial percentage of individuals who experience traumatic brain injury (TBI) [3]. Reports suggest that approximately 20%–68% of TBI patients exhibit trauma-associated olfactory deficits (OD) [3]. Even patients with mild TBI can experience persistent OD, with prevalence reported in up to 20% of cases [4].

Beyond TBI, other causes of acquired smell loss include upper respiratory infections (such as the common cold or flu) [5], and notably, it is a common symptom of COVID-19, experienced by almost 53% of those affected [1]. Upper airway inflammation, including rhinitis, rhinosinusitis, and nasal polyps, is also a frequent cause of gradual olfactory dysfunction. Neurodegenerative diseases, intracranial/sinonasal tumors, certain drugs, exposure to toxic substances, irradiation, or iatrogenic factors can also lead to anosmia [5].

Globally, a large number of people are affected; recent reports suggest approximately 20.5 million adults over forty in the United States suffer from olfactory dysfunction [6]. Head trauma accounts for about 5%–17% of acquired chemosensory dysfunction cases [7-9].

The significance of olfactory dysfunction is often underestimated, but it has a significant negative impact on patients’ quality of life and ability to accomplish daily activities [2,6]. OD can compromise not only the quality of life but also cognitive and neuropsychiatric functions [6], and can lead to issues like food poisoning, a reduction in appetite, malnutrition, and reduced immunity. Furthermore, olfactory function plays a crucial role in safety. Patients with olfactory impairment are at increased risk for personal injury, such as being unable to detect gas leaks, smoke, or spoiled foods. Studies show that a high percentage of patients with olfactory impairment have experienced hazardous events attributable to their loss of smell. Anosmia has also been associated with diminished satisfaction with life and an increased likelihood of depression [10,11].

Interestingly, anosmia can sometimes serve as an early clinical sign, potentially heralding the progression to dementia in TBI survivors, or serving as an early biomarker for the diagnosis and progression of neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease (AD) [12,13].

The diagnosis of anosmia requires objective olfactory testing, as self-assessment is often unreliable. Management often includes counseling regarding compensatory strategies to avoid safety risks and maximize quality of life [14].

1. Mechanisms of olfactory dysfunction

Post-traumatic OD can be classified as either conductive or neurosensory, depending on the injury location. Conductive deficits occur when odorants cannot reach the olfactory neuroepithelium, often due to physical obstruction like nasal bone fractures, septal deviation, mucosal edema, or hematoma [15]. Neurosensory deficits involve direct damage to the olfactory neuroepithelium or central olfactory pathways, including injury to the olfactory bulb. This can result from shearing of fibers at the cribriform plate or injury to the olfactory bulb itself. The prognosis for neurosensory deficits is generally poor, with many patients not recovering [16,17].

 Beyond Physical Damage, Inflammation Plays a Significant Role in Olfactory Dysfunction Associated with Various Conditions 1. Post-traumatic anosmia

Trauma-associated OD are common in TBI patients. Neuroanatomical and kinetic factors make the central olfactory structures, including the olfactory bulb, highly vulnerable to TBI-related damage [13]. Damage to the central components of olfactory pathways, such as the olfactory bulb, can cause post-traumatic olfactory dysfunction [18]. This can result from mechanisms like the shearing or stretching of olfactory nerve fibers at the cribriform plate, which directly affects the connection to the olfactory bulb, or from focal contusion or hemorrhage within the olfactory bulb itself [18]. Neurosensory deficits, in general, involve direct damage to the olfactory neuroepithelium or central olfactory pathways, including the olfactory bulb [19]. The prognosis for neurosensory deficits is often poor, with many patients not recovering. Experimental TBI studies in mice highlight significant inflammatory changes and neuronal dysfunction in the olfactory bulb. TBI in mice causes a rapid and sustained inflammatory response in the olfactory bulb, including elevated levels of pro-inflammatory cytokines, increased numbers of microglia and infiltrating by myeloid cells, and increased interleukin (IL)-1β and IL-6 production [20,21]. This neuroinflammation is accompanied by increased production of reactive oxygen species and upregulation of microglia/macrophages [22,23]. These changes are linked to neuronal dysfunction in the olfactory bulb, including early hyperexcitation and later hypo-neuronal activity, and contribute to OD [21].

 2. Chronic rhinosinusitis

Historically, OD in patients with sinusitis were primarily attributed to mechanical obstruction caused by nasal obstruction, respiratory mucosal edema, and decreased airflow to the olfactory cleft [19]. The assumption was that the olfactory mucosa remained histologically normal despite the aggressive inflammatory process in the respiratory regions of the nose. This view considered anosmia secondary to chronic rhinosinusitis (CRS) mainly as a “transport” disorder, where odorant molecules simply couldn’t reach the intact olfactory mucosa [24]. However, clinical studies have shown little correlation between nasal resistance and the degree of olfactory dysfunction, challenging the idea that obstruction is the sole cause [25]. Furthermore, surgical treatment for sinusitis and anosmia often has only limited effects on olfactory sensation despite successful resolution of other symptoms.

More recent studies, particularly a histological examination of olfactory biopsies from patients with chronic sinus disease, provide direct evidence for pathological changes within the olfactory mucosa itself [24]. This indicates that the pathological processes observed in the respiratory regions of the nose can also involve the olfactory mucosa. This suggests that olfactory loss with sinonasal inflammatory disease is a more complex process involving both transport and sensory pathology. Anosmia secondary to sinonasal disease involves direct effects on the olfactory mucosa (sensory disorder) in addition to any gross changes in airflow (transport disorder) [24]. Studies show inflammatory changes in the olfactory mucosa of patients with CRS, including infiltration of lymphocytes, macrophages, and eosinophils [26]. Moderate or severe inflammatory changes in the olfactory mucosa were observed in patients with decreased olfactory function [24]. This inflammation is likely to inhibit olfactory neurogenesis [27].

 3. COVID-19

COVID-19, caused by the SARS-CoV-2 virus, is a global pandemic that originated in Wuhan, China, in December 2019 [28]. It is a positive-sense single- stranded RNA virus [29]. One of the most common symptoms reported by patients with COVID-19 infection is olfactory dysfunction or anosmia [30]. The SARS-CoV-2 virus utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and the priming protease (transmembrane protease, serine 2) TMPRSS2 for entry into host cells. ACE2 receptors are found in various organs, including the respiratory cells and the central nervous system (CNS) [31]. The epithelium of the respiratory system is considered the primary site for initial coronavirus attachment [32]. Several mechanisms have been proposed to explain anosmia in COVID-19 patients:

1) Olfactory cleft obstruction

Nasal mucosal swelling and secretions can physically obstruct the olfactory cleft, preventing odor molecules from reaching the olfactory epithelium (OE) [33]. This is a “conductive” loss. However, anosmia can occur suddenly without nasal discharge or congestion, suggesting other mechanisms are involved. High expression of ACE2 receptors has been detected in the olfactory cleft region, and anosmic COVID-19 patients have shown significantly greater volume and area in the olfactory cleft compared to healthy controls [34].

 2) Local inflammation in the olfactory epithelium

High levels of ACE2 receptor expression are found on OE cells, particularly sustentacular cells [34,35]. The binding of the virus to these cells triggers the release of cytokines, promoting inflammation in the OE. Increased levels of pro-inflammatory cytokines like tumor necrosis factor (TNF)-α and IL-1β have been reported in OE biopsies from COVID-19 patients [36]. This inflammation in the OE is considered a probable mechanism for the quick recovery observed in many COVID-19-related anosmia cases. Since ACE2 is highly expressed in non-neuronal supporting cells rather than directly on olfactory neurons (ONs), the virus may primarily target these supporting cells, indirectly disrupting ON function.

 3) Role of interleukins

IL-6 is thought to play a significant role in anosmia, potentially activating apoptotic pathways or directly inhibiting the sense of smell [37]. Studies have found significant correlations between decreased levels of IL-6 and the time taken for recovery from anosmia in COVID-19 [38]. Viral infections, including influenza, have been associated with increased levels of IL-6, IL-12, IL-15, and TNF-α [39].

 4) Changes in olfactory cilia

Olfactory sensory neurons (OSNs) have cilia with receptors that detect odors. Viral infections, including COVID-19, may disrupt the structure and function of these cilia [40]. COVID-19 antigens have been found in ciliated nasal epithelial cells, and transmission electron microscopy showed absorption sites on cilia for viral entry. The Nsp13 protein of SARS-CoV-2 can bind to the centrosome of cilia, potentially disrupting their structure and leading to deciliation [41].

 5) Effect on olfactory bulbs

Some studies have investigated the impact of COVID-19 infection on the olfactory bulb as a potential mechanism for anosmia. It is hypothesized that the virus can enter the CNS by traveling along OSNs and crossing the cribriform plate to reach the olfactory bulbs [42]. MRI studies have identified instances of olfactory bulb injury secondary to COVID-19 infection [43].

 6) Damage to olfactory stem cells

In cases of persistent anosmia lasting for more than two months, damage to olfactory stem cells is considered a likely cause, delaying the regenerative capacity of the OE. Inflammation in the olfactory system is a critical factor for anosmia, and stem cell apoptosis can occur at sites of inflammation [44].

The prevalence and characteristics of COVID-19-related anosmia can vary based on several factors [1,45,46]:

 7) Age

Anosmia occurs less frequently at the extreme ends of age ranges and is most common in the 40- to 50-year age bracket. This difference might be related to age-related changes in sustentacular cells (which have high ACE2 expression) in older individuals and varying levels of nasal ACE2 gene expression with age [47].

 8) Disease severity

Patients with moderate to severe COVID-19 infections tend to report less olfactory involvement compared to those with mild infections. It is suggested that patients with mild disease might have a stronger local immune response in the nasal and olfactory mucosa and bulb, leading to a more pronounced otolaryngological symptom pattern. The upper airway has higher ACE2 expression than the lower airway and is thought to be the initial site of infection [48].

 9) Sex

Epidemiological data indicates that females are more likely to experience COVID-19-related olfactory dysfunction, although they are less likely to have severe infections. This difference may be linked to variations in ACE2 expression, innate immunity, steroid hormones, and factors related to sex chromosomes. The ACE2 gene is located on the X chromosome. Estrogen in females might reduce ACE2 expression compared to males, potentially resulting in lower viral load and reduced risk of severe disease. Women’s potentially stronger immune responses might lead to a more significant local inflammatory reaction in the OE, contributing to olfactory dysfunction [49].

 4. Neurodegenerative diseases

Olfactory dysfunction is an early symptom of many neurodegenerative diseases, particularly PD and AD, and may serve as an early biomarker [50]. In TBI survivors, OD may be an early sign of progression to dementia. The olfactory bulb is intricately connected to downstream olfactory centers, such as the piriform cortex and hippocampus. The hippocampus and entorhinal cortex are brain regions affected in the very early stages of AD [51]. The entorhinal cortex directly receives olfactory information and is part of a connection loop with the hippocampus and cortex, which is a main hub of network dysfunction in AD [52]. Studies in older adults free from dementia found that impaired olfactory identification was associated with lower volumes of the hippocampus and entorhinal cortex [53]. Post-mortem studies linked impaired odor identification with increased density of neurofibrillary tangles in the hippocampus and entorhinal cortex [53]. Olfactory identification impairment was also correlated with higher plasma total tau (t-tau) and neurofilament light chain concentrations, but not with plasma amyloid-beta [54]. This suggests that impaired odor identification may signify neurodegenerative processes and tau pathology in the brain, with negligible effects from amyloid pathology among dementia-free older adults [54]. Furthermore, impaired odor identification was associated with higher volumes of white matter hyperintensities (WMH) and periventricular WMH [55], markers of cerebral microvascular lesions [56]. These findings suggest that olfactory impairment and cognitive impairment may share common neuropathological bases related to neurodegeneration and vascular brain pathology.

 Conclusion

Anosmia is a complex clinical symptom with diverse etiologies, including TBI, CRS, viral infections such as COVID-19, and neurodegenerative diseases. Despite differences in initial triggers, these conditions converge on shared neurophysiological mechanisms, particularly neuroinflammation, disruption of olfactory epithelial and bulb integrity, impaired neuronal regeneration, and central olfactory network dysfunction. Inflammatory cytokines, oxidative stress, and structural damage to olfactory pathways are recurring features that underlie olfactory dysfunction across these diseases. Importantly, anosmia not only affects quality of life and safety but may also serve as an early biomarker of neurodegeneration. Understanding these overlapping mechanisms enhances our ability to develop targeted diagnostic tools and therapeutic strategies, emphasizing the need for interdisciplinary research bridging otolaryngology, neurology, and immunology.

Funding

This research was supported by the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (RS-2023-00220408), Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (RS-2025-00554060), and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (RS-2020-NR049585).

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Data Availability

None.

Author Contributions

Conceptualization: JHM; Writing–original draft: RV; Writing–review & editing: all authors.

 References NajaflooR MajidiJ AsghariA AleemardaniM KamravaSK SimorghS Mechanism of anosmia caused by symptoms of COVID-19 and emerging treatments ACS Chem Neurosci 2021 12 3795 805 doi: 10.1021/acschemneuro.1c00477 HowellJ CostanzoRM ReiterER Head trauma and olfactory function World J Otorhinolaryngol Head Neck Surg 2018 4 39 45 doi: 10.1016/j.wjorl.2018.02.001 LiuX LeiZ GilhoolyD HeJ LiY RitzelRM Traumatic brain injury-induced inflammatory changes in the olfactory bulb disrupt neuronal networks leading to olfactory dysfunction Brain Behav Immun 2023 114 22 45 doi: 10.1016/j.bbi.2023.08.004 ProskynitopoulosPJ StipplerM KasperEM Posttraumatic anosmia in patients with mild traumatic brain injury (mTBI): a systematic and illustrated review Surg Neurol Int 2016 7 S263 75 doi: 10.4103/2152-7806.181981 MullolJ Mariño-SánchezF VallsM AlobidI MarinC The sense of smell in chronic rhinosinusitis J Allergy Clin Immunol 2020 145 773 6 doi: 10.1016/j.jaci.2020.01.024 LiuG ZongG DotyRL SunQ Prevalence and risk factors of taste and smell impairment in a nationwide representative sample of the US population: a cross-sectional study BMJ Open 2016 6 e013246 doi: 10.1136/bmjopen-2016-013246 DuncanHJ SeidenAM Long-term follow-up of olfactory loss secondary to head trauma and upper respiratory tract infection Arch Otolaryngol Head Neck Surg 1995 121 1183 7 doi: 10.1001/archotol.1995.01890100087015 SchrieverVA StudtF SmitkaM GrosserK HummelT Olfactory function after mild head injury in children Chem Senses 2014 39 343 7 doi: 10.1093/chemse/bju005 TemmelAF QuintC Schickinger-FischerB KlimekL StollerE HummelT Characteristics of olfactory disorders in relation to major causes of olfactory loss Arch Otolaryngol Head Neck Surg 2002 128 635 41 doi: 10.1001/archotol.128.6.635 LiuDT PremB SharmaG KaiserJ BesserG MuellerCA Depression symptoms and olfactory-related quality of life Laryngoscope 2022 132 1829 34 doi: 10.1002/lary.30122 GopinathB AnsteyKJ SueCM KifleyA MitchellP Olfactory impairment in older adults is associated with depressive symptoms and poorer quality of life scores Am J Geriatr Psychiatry 2011 19 830 4 doi: 10.1097/JGP.0b013e318211c205 SchofieldPW MooreTM GardnerA Traumatic brain injury and olfaction: a systematic review Front Neurol 2014 5 5 doi: 10.3389/fneur.2014.00005 MarinC LangdonC AlobidI MullolJ Olfactory dysfunction in traumatic brain injury: the role of neurogenesis Curr Allergy Asthma Rep 2020 20 55 doi: 10.1007/s11882-020-00949-x ScangasGA BleierBS Anosmia: differential diagnosis, evaluation, and management Am J Rhinol Allergy 2017 31 3 7 doi: 10.2500/ajra.2017.31.4403 HummelT LiuDT MüllerCA StuckBA Welge-LüssenA HähnerA Olfactory dysfunction: etiology, diagnosis, and treatment Dtsch Arztebl Int 2023 120 146 54 doi: 10.3238/arztebl.m2022.0411 MehkriY HannaC SriramS ReddyR HernandezJ ValisnoJA Overview of neurotrauma and sensory loss J Neurol Res Rev Rep 2022 4 1 7 doi: 10.47363/JNRRR/2022(4)158 De LucaR BonannoM RificiC QuartaroneA CalabròRS Post-traumatic olfactory dysfunction: a scoping review of assessment and rehabilitation approaches Front Neurol 2023 14 1193406 doi: 10.3389/fneur.2023.1193406 CoelhoDH CostanzoRM Posttraumatic olfactory dysfunction Auris Nasus Larynx 2016 43 137 43 doi: 10.1016/j.anl.2015.08.006 GoncalvesS GoldsteinBJ Pathophysiology of olfactory disorders and potential treatment strategies Curr Otorhinolaryngol Rep 2016 4 115 21 doi: 10.1007/s40136-016-0113-5 LaFeverBJ KawasawaYI ItoA ImamuraF Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons Brain Behav Immun Health 2022 21 100451 doi: 10.1016/j.bbih.2022.100451 LaFeverBJ ImamuraF Effects of nasal inflammation on the olfactory bulb J Neuroinflammation 2022 19 294 doi: 10.1186/s12974-022-02657-x SeoY KimHS KangKS Microglial involvement in the development of olfactory dysfunction J Vet Sci 2018 19 319 30 doi: 10.4142/jvs.2018.19.3.319 YuY YuZ XieM WangW LuoX Hv1 proton channel facilitates production of ROS and pro-inflammatory cytokines in microglia and enhances oligodendrocyte progenitor cells damage from oxygen-glucose deprivation in vitro Biochem Biophys Res Commun 2018 498 1 8 doi: 10.1016/j.bbrc.2017.06.197 YeeKK PribitkinEA CowartBJ VainiusAA KlockCT RosenD Neuropathology of the olfactory mucosa in chronic rhinosinusitis Am J Rhinol Allergy 2010 24 110 20 doi: 10.2500/ajra.2010.24.3435 KernRC Chronic sinusitis and anosmia: pathologic changes in the olfactory mucosa Laryngoscope 2000 110 1071 7 doi: 10.1097/00005537-200007000-00001 KohliP NaikAN HarruffEE NguyenSA SchlosserRJ SolerZM The prevalence of olfactory dysfunction in chronic rhinosinusitis Laryngoscope 2017 127 309 20 doi: 10.1002/lary.26316 YanX WhitcroftKL HummelT Olfaction: sensitive indicator of inflammatory burden in chronic rhinosinusitis Laryngoscope Investig Otolaryngol 2020 5 992 1002 doi: 10.1002/lio2.485 AdilMT RahmanR WhitelawD JainV Al-TaanO RashidF SARS-CoV-2 and the pandemic of COVID-19 Postgrad Med J 2021 97 110 6 doi: 10.1136/postgradmedj-2020-138386 V’kovskiP KratzelA SteinerS StalderH ThielV Coronavirus biology and replication: implications for SARS-CoV-2 Nat Rev Microbiol 2021 19 155 70 doi: 10.1038/s41579-020-00468-6 SedaghatAR GenglerI SpethMM Olfactory dysfunction: a highly prevalent symptom of COVID-19 with public health significance Otolaryngol Head Neck Surg 2020 163 12 5 doi: 10.1177/0194599820926464 BarrantesFJ Central nervous system targets and routes for SARS-CoV-2: current views and new hypotheses ACS Chem Neurosci 2020 11 2793 803 doi: 10.1021/acschemneuro.0c00434 LeštarevićS SavićS VitkovićL MandićP MijovićM DejanovićM Respiratory epithelium: place of entry and / or defense against SARS-CoV-2 virus Prax Med 2021 50 35 43 doi: 10.5937/pramed2102035L TrotierD BensimonJL HermanP Tran Ba HuyP DøvingKB EloitC Inflammatory obstruction of the olfactory clefts and olfactory loss in humans: a new syndrome? Chem Senses 2007 32 285 92 doi: 10.1093/chemse/bjl057 ChenM ShenW RowanNR KulagaH HillelA RamanathanMJr Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication Eur Respir J 2020 56 2001948 doi: 10.1183/13993003.01948-2020 KlingensteinM KlingensteinS NeckelPH MackAF WagnerAP KlegerA Evidence of SARSCoV2 entry protein ACE2 in the human nose and olfactory bulb Cells Tissues Organs 2020 209 155 64 doi: 10.1159/000513040 FaraA MitrevZ RosaliaRA AssasBM Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines Open Biol 2020 10 200160 doi: 10.1098/rsob.200160 CazzollaAP LoveroR Lo MuzioL TestaNF SchirinziA PalmieriG Taste and smell disorders in COVID-19 patients: role of interleukin-6 ACS Chem Neurosci 2020 11 2774 81 doi: 10.1021/acschemneuro.0c00447 ArulkumaranN SnowTAC KulkarniA BrealeyD RickmanHM Rees-SpearC Influence of IL-6 levels on patient survival in COVID-19 J Crit Care 2021 66 123 5 doi: 10.1016/j.jcrc.2021.08.013 BrydonEW MorrisSJ SweetC Role of apoptosis and cytokines in influenza virus morbidity FEMS Microbiol Rev 2005 29 837 50 doi: 10.1016/j.femsre.2004.12.003 DaiX XuR LiN The interplay between airway cilia and coronavirus infection, implications for prevention and control of airway viral infections Cells 2024 13 1353 doi: 10.3390/cells13161353 LiW LiM OuG COVID-19, cilia, and smell FEBS J 2020 287 3672 6 doi: 10.1111/febs.15491 BauerL LaksonoBM de VrijFMS KushnerSA HarschnitzO van RielD The neuroinvasiveness, neurotropism, and neurovirulence of SARS-CoV-2 Trends Neurosci 2022 45 358 68 doi: 10.1016/j.tins.2022.02.006 AragãoMFVV LealMC Cartaxo FilhoOQ FonsecaTM ValençaMM Anosmia in COVID-19 associated with injury to the olfactory bulbs evident on MRI AJNR Am J Neuroradiol 2020 41 1703 6 doi: 10.3174/ajnr.A6675 VermaAK ZhengJ MeyerholzDK PerlmanS SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways JCI Insight 2022 7 e160277 doi: 10.1172/jci.insight.160277 KumarAA LeeSWY LockC KeongNC Geographical variations in host predisposition to COVID-19 related anosmia, ageusia, and neurological syndromes Front Med (Lausanne) 2021 8 661359 doi: 10.3389/fmed.2021.661359 KaramaliK ElliottM HopkinsC COVID-19 related olfactory dysfunction Curr Opin Otolaryngol Head Neck Surg 2022 30 19 25 doi: 10.1097/MOO.0000000000000783 BrechbühlJ LopesAC WoodD BouteillerS de VallièreA VerdumoC Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms Commun Biol 2021 4 880 doi: 10.1038/s42003-021-02410-9 LeeIT NakayamaT WuCT GoltsevY JiangS GallPA ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs Nat Commun 2020 11 5453 doi: 10.1038/s41467-020-19145-6 MeleD CalastriA MaioranoE CerinoA SachsM OlivieroB High frequencies of functional virus-specific CD4+ T cells in SARS-CoV-2 subjects with olfactory and taste disorders Front Immunol 2021 12 748881 doi: 10.3389/fimmu.2021.748881 Bhatia-DeyN HeinbockelT The olfactory system as marker of neurodegeneration in aging, neurological and neuropsychiatric disorders Int J Environ Res Public Health 2021 18 6976 doi: 10.3390/ijerph18136976 SlabikD GaraschukO Olfactory dysfunction as a common biomarker for neurodegenerative and neuropsychiatric disorders Neural Regen Res 2023 18 1029 30 doi: 10.4103/1673-5374.355756 ScharfmanHE ChaoMV The entorhinal cortex and neurotrophin signaling in Alzheimer’s disease and other disorders Cogn Neurosci 2013 4 123 35 doi: 10.1080/17588928.2013.826184 KubotaS MasaokaY SugiyamaH YoshidaM YoshikawaA KoiwaN Hippocampus and parahippocampus volume reduction associated with impaired olfactory abilities in subjects without evidence of cognitive decline Front Hum Neurosci 2020 14 556519 doi: 10.3389/fnhum.2020.556519 AbedSS HamdanFB HusseinMM Al-MayahQS Plasma tau and neurofilament light chain as biomarkers of Alzheimer’s disease and their relation to cognitive functions J Med Life 2023 16 284 9 doi: 10.25122/jml-2022-0251 HamJH LeeJJ SunwooMK HongJY SohnYH LeePH Effect of olfactory impairment and white matter hyperintensities on cognition in Parkinson’s disease Parkinsonism Relat Disord 2016 24 95 9 doi: 10.1016/j.parkreldis.2015.12.017 RyuSY LeeDC LeeSB KimTW LeeTJ YangPS Olfactory identification and white matter integrity in amnestic mild cognitive impairment: a preliminary study Int J Imaging Syst Technol 2016 26 270 6 doi: 10.1002/ima.22198