COVID-19's lasting mark: Long-term smell and taste loss

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Feb 29 2024

A recent study published in Life investigates the mechanisms responsible for severe olfactory dysfunction (OD) and gustatory dysfunction (GD) following recovery from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Study: Persistent Olfactory and Taste Dysfunction after COVID-19. Image Credit: DimaBerlin / Shutterstock.com

Background

SARS-CoV-2 is the causal agent of the coronavirus disease 2019 (COVID-19). A sudden loss of smell or taste is one of the most common symptoms of SARS-CoV-2 infection.

Typically, OD and GD occur in the early phase of the infection, which has led these symptoms to be used as a screening tool for COVID-19. Both OD and GD occur primarily among young patients and are independent of gender.

COVID-19 patients with OD often experience a spontaneous return of their sense of smell to pre-symptomatic levels within one month of infection. However, between 7-20% of COVID-19 patients report prolonged OD, even after other symptoms have resolved.

Mechanistically, patients with severe nasal and sinus symptoms undergo swelling of the mucous membranes of the olfactory cleft, which increases mucus secretion. This increase in mucus causes a mechanical blockage to odor molecules, manifesting as conductive OD. Infiltration of viral particles into the non-neural cells of the olfactory epithelium also induces significant immune responses.

In the context of immune responses to viral infiltration into olfactory epithelium, pro-inflammatory cytokines such as interleukin 1 β (IL-1β) and tumor necrosis factor α (TNF- α) are released. The impaired non-neural cells subsequently disrupt the connection between nerve cells and sensory OD, which inhibits the transfer of olfactory stimuli to the brain.

Importantly, the precise mechanism of action on the penetration of SARS-CoV-2 into the central nervous system remains unclear. One possible mechanism could be the direct penetration of SARS-CoV-2 into the cerebrospinal fluid from non-neural cells of the olfactory epithelium.

The penetration of SARS-CoV-2 into the olfactory neuroepithelium causing sensorineural OD has been well documented. In this context, the spike (S) protein of SARS-CoV-2 binds to the angiotensin-converting-enzyme-2 (ACE2) receptor, which triggers the synthesis of the transmembrane serine protease 2 (TMPRSS2), thereby causing membrane fusion.

To date, few studies have elucidated the mechanism that underlies the manifestation of GD due to COVID-19.

About the study

The current prospective and single-center study involved a subjective and physical examination of patients. Study participants also underwent multiple olfactory and gustatory tests, such as the Sniffin’ Sticks Test (SST) and Taste Strips Test (TS).

A total of 81 participants were recruited, including 16 men and 65 women between 12 and 73 years of age. All participants experienced OD due to COVID-19, which persisted for at least one month after the resolution of other acute symptoms.

Study findings

The study participants experienced persistent OD or GD (OGD) with durations ranging between one and 25 months.

Few clinical facilities offer help to patients with persistent OGD following recovery from COVID-19. This could be because clinicians are still developing their knowledge regarding long-term COVID and formulating strategies to combat the condition. Additionally, patients often seek treatment for OD only after resolving more serious symptoms.

The degree of damage in the olfactory cells by SARS-CoV-2 penetration dictates the duration of OD. For conductive disorders that occur in most infected individuals, the sense of smell improves after a reduction in acute inflammation of the nasal mucosa. Patients with damaged olfactory cells exhibit persistent OD, as neurons take longer to recover and re-establish adequate intercellular connections.

About 64% of the study participants had hyposmia, and 22% had functional anosmia. SST scores revealed that the participants scored lowest on the threshold part of the test. The SST score of other parts concerning discrimination and identification of odor revealed that patients could sense intense smell correctly.

SST scores significantly depend on the function of the olfactory epithelium, which suggests that post-COVID-19 OD is predominantly associated with damage in peripheral olfactory due to acute immune responses. More specifically, the cytokine storm leads to leukocytic infiltration and disrupts olfactory epithelial cells, including stem cells.

There was no difference in recognizing odorants that stimulate only the olfactory nerve and those that trigger the trigeminal nerve, such as mint and lemon. Interestingly, some participants with subjective ODs scored within a normal range on the SST test. 

Around 17% of participants reported abnormal taste. The best-recognized taste was sweet, followed by salty. Only bitter taste was marginally correlated with TTS and TS scores.

Conclusions

The findings provide important insights into the relationship between OD and SARS-CoV-2 infection. It is possible that the relationship between OD and COVID-19 is more peripheral than central; therefore, clinicians must pay close attention to the condition of the nasal mucosa and provide better information to patients about good nasal hygiene that can help alleviate the condition.