Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication

Chen, Mengfei; Shen, Wenjuan; Rowan, Nicholas R.; Kulaga, Heather; Hillel, Alexander T.; Ramanathan, Murugappan; Lane, Andrew P.

doi:10.1183/13993003.01948-2020

Cited by 211 publications

(219 citation statements)

References 20 publications

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“…The utilization of the olfactory route is further supported by the fact that issues with smell have been reported internationally, reporting a prevalence as high as 85% in a large, multicenter European survey (Lechien et al., 2020). Furthermore, high‐intensity ACE2 staining was detected in olfactory mucosal biopsies, with a 200‐ to 700‐fold ACE2 enrichment in the olfactory neuroepithelium (sustentacular cells) relative to the nasal respiratory or tracheal epithelial cells (Chen, Shen, et al, 2020). This cellular tropism of SARS‐CoV‐2 may underlie its high transmissibility and association with dysfunction of olfactory neuroepithelium receptors in the nasal and oral mucosa, and also suggests the existence of a viral reservoir that may be a good candidate for intranasal therapy.…”

Section: Olfactory Route (Oe)mentioning

confidence: 99%

“…This cellular tropism of SARS‐CoV‐2 may underlie its high transmissibility and association with dysfunction of olfactory neuroepithelium receptors in the nasal and oral mucosa, and also suggests the existence of a viral reservoir that may be a good candidate for intranasal therapy. In contrast, ACE2 was not found in immature and mature olfactory neurons (Chen, Shen, et al, 2020). Taken together, these observations of the enhanced expression of ACE2 localized to the olfactory neuroepithelium of the human airway suggests that COVID‐19 infection and replication may take place in the apical layer of nasal and olfactory mucosa, resulting in olfactory loss and acting as a possible entry point of the virus into the CNS, causing neurological symptoms (Chen, Shen, et al, 2020; Mao et al., 2020).…”

Section: Olfactory Route (Oe)mentioning

confidence: 99%

“…In contrast, ACE2 was not found in immature and mature olfactory neurons (Chen, Shen, et al, 2020). Taken together, these observations of the enhanced expression of ACE2 localized to the olfactory neuroepithelium of the human airway suggests that COVID‐19 infection and replication may take place in the apical layer of nasal and olfactory mucosa, resulting in olfactory loss and acting as a possible entry point of the virus into the CNS, causing neurological symptoms (Chen, Shen, et al, 2020; Mao et al., 2020). Furthermore, although the postmortem examination showed no inflammatory infiltrates or neuronal necrosis in the brains of the deceased COVID‐19 patients analyzed histologically, and although the SARS‐CoV‐2 RNA copy numbers were predominantly low in the brain, the corresponding values detected in the olfactory bulb were higher than those in the brainstem, supporting the hypothesis of the viral entry into the brain via the lamina cribrosa (Menter et al., 2020).…”

Section: Olfactory Route (Oe)mentioning

confidence: 99%

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Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

Uversky

Elrashdy

Aljadawi

et al. 2020

J of Neuroscience Research

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Without protective and/or therapeutic agents the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection known as coronavirus disease 2019 is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS‐CoV‐2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS‐CoV‐2 components could use to reach the CNS and PNS, utilizing the within‐body cross talk between organs. The majority of SARS‐CoV‐2–infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune‐mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood–endothelial barrier may be considered as the main route for SARS‐CoV‐2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

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Section: Olfactory Route (Oe)mentioning

confidence: 99%

Section: Olfactory Route (Oe)mentioning

confidence: 99%

Section: Olfactory Route (Oe)mentioning

confidence: 99%

See 1 more Smart Citation

Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

Uversky

Elrashdy

Aljadawi

et al. 2020

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…In the nasal cavity, the special olfactory neuroepithelium has an apical surface mainly composed of support cells, supporting the dendritic processes of neurons containing olfactory cilia ( 38 ). The dendrites of olfactory neurons are directly exposed in the airway of the nose ( 10 ).…”

Section: Three Mechanisms Of Sars-cov-2 Invading the Nervous Systemmentioning

confidence: 99%

Progress in Research on SARS-CoV-2 Infection Causing Neurological Diseases and Its Infection Mechanism

Wang

Ren

et al. 2021

Front. Neurol.

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COVID-19 has spread rapidly worldwide since its outbreak and has now become a major public health problem. More and more evidence indicates that SARS-CoV-2 may not only affect the respiratory system but also cause great harm to the central nervous system. Therefore, it is extremely important to explore in-depth the impact of SARS-CoV-2 infection on the nervous system. In this paper, the possible mechanisms of SARS-CoV-2 invading the central nervous system during COVID-19, and the neurological complications caused by SARS-CoV-2 infection were reviewed.

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“…In fact, obese young patients showing increased ACE2 expression in lung epithelial cells are typically characterized by the increased severity of COVID-19 [161,162]. On the other hand, relative to the upper airway epithelial cells, the human olfactory epithelium shows higher levels of the expressed ACE2 protein, suggesting that the initial site of SARS-CoV-2 infection is the upper, rather than the lower, airway [163]. These important findings provide an explanation for the COVID-19-associated olfactory dysfunction, such as common disturbances in the sense of smell, which were reported in 85% COVID-19 patients who participated in a large, multicenter European survey [164].…”

Section: Human (Host) Factorsmentioning

confidence: 99%

Why COVID-19 Transmission Is More Efficient and Aggressive Than Viral Transmission in Previous Coronavirus Epidemics?

2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face a microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (severe acute respiratory syndrome (SARS-CoV) and middle east respiratory syndrome (MERS-CoV)) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summarize the possible and logical answers to these questions.

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Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication

Cited by 211 publications

References 20 publications

Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

Progress in Research on SARS-CoV-2 Infection Causing Neurological Diseases and Its Infection Mechanism

Why COVID-19 Transmission Is More Efficient and Aggressive Than Viral Transmission in Previous Coronavirus Epidemics?

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