Olfactory dysfunction in SARS-CoV-2 infection: Focus on odorant specificity and chronic persistence

Abstract

Background Smell dysfunction has been recognized as an early symptom of SARS-CoV-2 infection, often occurring before the onset of core symptoms of the respiratory tract, fever or muscle pain. In most cases, olfactory dysfunction is accompanied by reduced sense of taste, is partial (microsmia) and seems to normalize after several weeks, however, especially in cases of virus-induced complete smell loss (anosmia), there are indications of persisting deficits even 2 months after recovery from the acute disease, pointing towards the possibility of chronic or even permanent smell reduction for a significant part of the patient population. To date, we have no knowledge on the specificity of anosmia towards specific odorants or chemicals and about the longer-term timeline of its persistence or reversal. Methods In this longitudinal study, 70 participants from a community in Lower Austria that had been tested positive for either IgG or IgM SARS-CoV-2 titers in June 2020 and a healthy control cohort ( N = 348) underwent smell testing with a 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon items from the University of Pennsylvania Smell Identification Test (UPSIT). The test was performed in October 2020, i.e. 4 months after initial diagnosis via antibody testing. Results were analyzed using statistical tests for contingency for each smell individually in order to detect whether reacquisition of smell is dependent on specific odorant types. Results For all odorants tested, except the odor “smoke”, even 4 months or more after acute SARS-CoV-2 infection, participants with a positive antibody titer had a reduced sense of smell when compared to the control group. On average, while the control cohort detected a set of 12 different smells with 88.0% accuracy, the antibody-positive group detected 80.0% of tested odorants. A reduction of accuracy of detection by 9.1% in the antibody-positive cohort was detected. Recovery of the ability to smell was particularly delayed for three odorants: strawberry (encoded by the aldehyde ethylmethylphenylglycidate), lemon (encoded by citronellal, a monoterpenoid aldehyde), and soap (alkali metal salts of the fatty acids plus odorous additives) exhibit a sensitivity of detection of an infection with SARS-CoV-2 of 31.0%, 41.0% and 40.0%, respectively. Conclusion Four months or more after acute infection, smell performance of SARS-CoV-2 positive patients with mild or no symptoms is not fully recovered, whereby the ability to detect certain odors (strawberry, lemon and soap) is particularly affected, suggesting the possibility that these sensitivity to these smells may not only be lagging behind but may be more permanently affected.

Phantosmia, Parosmia, and Dysgeusia Are Prolonged and Late-Onset Symptoms of COVID-19

“…Consistent with several other studies, our study corroborates that dysfunctions of taste and smell are early onset symptoms of COVID-19 [22][23][24][25] and persist in many cases for several months [13,[26][27][28]. It was evident that qualitative changes (parosmia, phantosmia and dysgeusia) can occur as late-onset symptoms.…”

The residual effect of coronovirus disease 2019 on olfactory acuity and mucociliary clearance time: a cross-sectional, controlled study

“…18 Rebholz et al also indicated the dominant role of olfactory neural loss in long-lasting hyposmia. 12 We may speculate that subclinical ongoing inflammation affecting the olfactory neuroepithelium or temporary or permanent loss of regeneration ability of the olfactory neuroepithelium because of progenitor and stem cell degeneration may be the reason for persistent olfactory dysfunction. Child et al confirmed that olfactory stem cells have limited neuroregenerative capacity.…”

“…Rebholz et al also found that the perception of certain odours (lemon, soap and strawberry) was delayed in the recovery period, and they believed that this could be because of the more difficult or slower regeneration process of associated odour-specific neurons. 12 The exact mechanism underlying this odourspecific misperception is not clear. Like Rebholz et al, we think that delayed recovery in this specific subset of neurons could be the answer.…”

“…It usually subsides within a few weeks; however, in some cases, symptoms may persist for months after the infection. 12,13 Therefore, our primary objective was to determine the residual effects of Covid-19 on olfaction, mucociliary clearance and sinonasal functions. Secondly, there are studies reporting that individuals underestimate their hyposmia through self-reporting.…”

“…(11)(12))** <0.001 † *Group 1 had significantly higher Sino-Nasal Outcome Test (SNOT)-22 scores than group 2 and group 3 ( p = 0.004 and p < 0.001). Group 2 and group 3 scores were similar ( p = 0.30).…”