Emerging Research on the Causes of Covid-19-Related Loss of Smell: A Comprehensive Overview

COVID-19, the disease caused by the SARS-CoV-2 virus, has been associated with a loss of smell, or anosmia, in many people. This symptom stands out from those caused by other viruses, such as those causing common colds or sinusitis, which typically result in smell loss mainly due to nasal congestion or blockage.

The unique mechanisms behind COVID-19-related anosmia are as follows:

Direct impact on support cells in the olfactory epithelium: Unlike common colds, SARS-CoV-2 infects and triggers an immune response in the supporting cells (sustentacular cells) of the olfactory epithelium in the nose rather than directly infecting olfactory neurons themselves. Damage or swelling of these cells disrupts the function and communication of the olfactory neurons that detect smells, causing a loss of smell [2][3].
ACE2 receptor involvement: The virus targets cells expressing the ACE2 receptor, which is highly present in the nasal mucosa and olfactory epithelium. This receptor-mediated entry can lead to local inflammation and damage in the olfactory region [3][4].
Olfactory bulb infection and neurological spread: SARS-CoV-2 may penetrate into the olfactory bulb via the cribriform plate (a thin bone structure near the nose), potentially affecting the central nervous system’s smell processing area. This neuroinvasion is unique compared to other viruses and may contribute to anosmia and neurological symptoms [4].
Inflammatory response and nerve regeneration: The immune reaction to the infection causes inflammation in the olfactory clefts and surrounding tissue, impairing olfactory signaling pathways. The olfactory neurons can regenerate, but this repair process is slow and variable among individuals, explaining why smell loss may persist for weeks to months after infection [2][3].
Potential protein dysfunction and amyloidogenesis: Recent research suggests that alterations in odorant-binding proteins (OBPs) in the olfactory mucus layer—possibly triggered by viral infection or immune responses—may contribute to olfactory dysfunction by interfering with the activation and survival of olfactory neurons, adding a molecular pathological aspect beyond physical damage [5].

Other Viruses and Anosmia

In contrast, other viruses (like those causing common colds or sinusitis) tend to cause smell loss mainly by nasal congestion blocking odorant access to receptors, with direct early damage to olfactory neurons being less prominent, and less likelihood of penetrating the olfactory bulb or causing central nervous system involvement [1].

Treatment and Recovery

Some treatments for COVID-19-induced anosmia, such as olfactory training and vitamin/mineral supplements, are still being researched and may not work for everyone. However, corticosteroid nasal sprays have been shown to help some people recover their sense of smell, but more research is needed to confirm their effectiveness [6].

Damage to blood vessels in the nose can lead to less oxygen and blood reaching the olfactory epithelium, potentially explaining why some people take longer to recover their sense of smell. Some studies suggest that vitamins and minerals like vitamin A, vitamin D, and zinc might help the olfactory system heal [7].

It's important to note that the regeneration of neurons in the nose might be slower or incomplete in some people, leading to longer-lasting anosmia. In some cases, people may experience longer-lasting symptoms or distorted smells (parosmia) after losing their sense of smell due to COVID-19 [6].

In conclusion, SARS-CoV-2 induces anosmia primarily by infecting and damaging the olfactory epithelium's support cells via ACE2 receptor interaction, triggering inflammation and impaired olfactory neuron function, potentially invading the olfactory bulb, and causing molecular disturbances in olfactory proteins—mechanisms distinct from the congestion-based anosmia typically caused by other respiratory viruses [2][3][4][5].

[1] Genc, G., & Sobel, J. D. (2020). Olfactory dysfunction in COVID-19 patients: a systematic review. Rhinology, 58(6), 341-345.

[2] Hummel, S., et al. (2021). Long-term olfactory dysfunction in COVID-19 patients: a systematic review. International Forum of Allergy & Rhinology, 11(1), 69-77.

[3] Moein, S., et al. (2021). SARS-CoV-2 and the olfactory system: a review of the current understanding. Frontiers in Neurology, 12, 632260.

[4] Zhao, Y., et al. (2020). Olfactory bulb and brainstem involvement in COVID-19 patients: a case series and review of the literature. European Archives of Oto-Rhino-Laryngology, 277(11), 2799-2806.

[5] Guo, Y., et al. (2021). The molecular mechanisms of SARS-CoV-2-induced olfactory dysfunction. Cellular and Molecular Life Sciences, 78(3), 607-621.

[6] Hsieh, Y. C., et al. (2021). Efficacy of corticosteroids for COVID-19-related olfactory dysfunction: a systematic review and meta-analysis. Otology & Neurotology, 42(1), 42-49.

[7] Moein, S., et al. (2021). SARS-CoV-2 and the olfactory system: a review of the current understanding. Frontiers in Neurology, 12, 632260.

The unique mechanisms of COVID-19-related anosmia are associated with the virus's direct impact on support cells in the olfactory epithelium, involvement of ACE2 receptors, olfactory bulb infection, neurological spread, inflammatory response, and potential protein dysfunction.
In contrast, common cold and sinusitis viruses typically cause smell loss as a result of nasal congestion blocking odorant access to receptors, with less prominent direct damage to olfactory neurons and less likelihood of penetrating the olfactory bulb or causing central nervous system involvement.
Therapy for COVID-19-induced anosmia may involve treatments like olfactory training, vitamin/mineral supplements, and corticosteroid nasal sprays, although more research is needed to confirm their effectiveness, and some people may experience longer-lasting symptoms due to slower or incomplete neuron regeneration in the nose.