A Comparative Evaluation of Taste and Smell Dysfunction in COVID-19: A Cross-sectional Study

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Moein, Amir H. Dehqan, Hamid Reza Baradaran, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7917937/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Taste and smell dysfunction are hallmark symptoms ofCoronavirus Disease (COVID-19). While objective assessment of chemosensory function is critical for accurate evaluation, most prior studies have relied on self-report measures, and data from non-Western populations remain limited. Objective: To objectively assess gustatory and olfactory function in recently diagnosed COVID-19 patients compared to age- and sex-matched healthy controls using validated tools in an Iranian population. Methods: In this prospective cross-sectional study, 30 COVID-19 patients and 30 matched healthy controls were enrolled between February and March 2022 in Tehran, Iran. Gustatory function was assessed using the Waterless Empirical Taste Test (WETT), and olfactory function was evaluated using the Pocket Smell Test (PST). Results: COVID-19 patients demonstrated significantly lower mean WETT scores compared to controls [16.14 (SD= 4.06) vs. 18.73 (SD=5.06), p < 0.05], with sour, bitter, and umami tastes significantly affected. Smell scores were also significantly lower among patients [6 (Interquartile Range (IQR)=5–7) vs. 7 (IQR=6–8), p < 0.05]. Among COVID-19 patients, 10% were anosmic and 56.7% microsmic. The odds of smell dysfunction were significantly higher in the COVID-19 group (OR = 4.67, 95% CI: 1.57–13.87). Conclusion: COVID-19 is associated with measurable impairments in both gustatory and olfactory function, particularly in sour, bitter, and umami modalities. There wasn’t any correlation between olfactory and gustatory test scores. Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Olfaction function Smell dysfunction Gustatory function Taste dysfunction COVID-19 Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Taste and smell are essential chemical senses that play a crucial role in nutrition, safety, and overall well-being and they are tied to memory, emotion, and social behaviours [ 1 ]. Dysfunction in these systems can lead to nutritional imbalances, increased risk from environmental hazards, and significant impacts on mental health and quality of life [ 2 ]. The Coronavirus Disease (COVID-19) pandemic brought unprecedented global attention to chemosensory changes as one of the early symptoms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection often occurs even in mild or asymptomatic cases [ 3 , 4 ]. This chemosensory loss presents as anosmia/hyposmia or agusia/hypogusia, distinguishes COVID-19 from many other respiratory viruses, and can sometimes present as the sole clinical manifestation [ 5 – 8 ]. Chemosensory loss contributes to the burden of COVID-19 by affecting individuals’ quality of life, interpersonal interaction, mental health, and safety [ 9 ]. Additionally, chemosensory symptoms, while often considered minor, may carry broader neurological implications due to their anatomical pathway, projecting directly to limbic and memory-related brain regions such as the hippocampus, amygdala, and orbitofrontal cortex [ 10 ]. While the exact mechanisms are still under investigation, current evidence points to multiple pathways. The mechanisms behind gustatory dysfunction in COVID-19 are likely multifactorial. Experimental studies have confirmed that SARS-CoV-2 can directly infect and replicate in taste bud cells, further supporting a biological basis for the observed taste loss in COVID-19. On a cellular level, Type II taste receptor cells, which detect sweet, bitter, and umami, express ACE2, making them direct targets for viral entry [ 11 – 13 ]. These cells are also responsive to inflammation via Toll-like receptors and downstream NF-κB signaling, which can impair their lifespan and renewal. The underlying pathophysiology of COVID-19-related smell loss appears to involve both direct and indirect mechanisms within the olfactory epithelium (OE). SARS-CoV-2 primarily targets sustentacular (SUS) cells, which express ACE2 and TMPRSS2, rather than the olfactory sensory neurons (OSNs) themselves [ 14 , 15 ]. Infection of these support cells leads to epithelial disorganization, inflammatory infiltration, and disrupted neuronal function [ 16 ]. Neuro-inflammation, invasion of the virus to the Central Nervous System (CNS) and damage to the olfactory and trigeminal nerve, which leads to olfactory and gustatory dysfunction. Nasal symptoms such as nasal congestion, can be a reason for olfactory dysfunction[ 10 ]. Moreover, the viral infection and inflammation reduce the progenitor cell renewal, while they increase taste cell death [ 17 ]. The reported prevalence of COVID-19-associated chemosensory dysfunction varies widely across studies from 5% to over 98% for smell and 6% to 93% for taste dysfunction, influenced by factors such as the viral variant, population demographics, disease severity, and importantly, the method of assessment. Self-reported symptoms, while easy to collect, are known to be unreliable. A Systematic reviews and meta-analysis study has demonstrated that objective direct testing methods reveal significantly higher prevalence rates of olfactory loss compared to subjective self-reports, highlighting the critical need for standardized, validated measures in research and clinical assessment [ 18 ]. Taste loss has often been misinterpreted as smell loss, and it was indicated that self-reported taste scores are better correlated with olfactory scores, rather than gustatory function [ 19 ].. The sensitivity and specificity of the self-report measures in assessing taste dysfunction in patients with COVID-19 are reported to be low [ 20 ]. Importantly, while some studies have applied objective tools to assess long-term outcomes of chemosensory dysfunction, very few have focused on the acute or subacute phases of COVID-19, particularly in non-Western populations. A meta-analysis on taste loss following COVID-19 reported that among 138,897 individuals diagnosed with COVID-19, only 257 were evaluated using standardized objective taste tests[ 4 ]. Studies examining different taste qualities, such as sweet, salty, sour, bitter, and umami, are especially limited. To address these gaps, the present study aimed to objectively evaluate gustatory and olfactory functions using validated tools in recently diagnosed COVID-19 patients compared with a well-matched healthy control group within an Iranian population. Methods Study design and setting: This prospective, analytical, cross-sectional study was conducted between February and March 2022 in tertiary hospitals affiliated with Iran University of Medical Sciences, Tehran, Iran, in collaboration with the Institute for Research in Fundamental Sciences, Tehran, Iran. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies [ 21 ]. The Ethics Committee of Iran University of Medical Sciences approved this study with the reference number IR.IUMS.FMD.REC.1400.598, and it was conducted in accordance with the latest version of the Helsinki Declaration. Participants: Patients with confirmed COVID-19 and healthy controls were enrolled using a combination of consecutive sampling for cases and matched sampling for controls. Eligible participants who provided written informed consent were included in the study. The inclusion criteria for the patient group involve adults aged 17 to 70 years with a positive Real-Time reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 from nasopharyngeal swab samples. The exclusion criteria involve pregnancy, chronic sinusitis, and a history of traumatic head injury. Patients with COVID-19 confirmed with RT-PCR who fulfilled eligibility criteria were enrolled consecutively from Firoozgar Hospital and Rasool Akram Hospital between February and March 2022. Inclusion criteria required patients aged between 18 and 70 years. Individuals were excluded if they were pregnant or had a history of chronic sinusitis, traumatic head injury, or any other physiological or structural condition affecting taste or smell. COVID-19 patients meeting the eligibility criteria were recruited consecutively from the infectious disease wards of Firoozgar and Rasool Akram Hospitals during the study period. Healthy controls were selected from the general population and matched to patients based on age and gender. They had no history of respiratory tract infections in the past three months, as confirmed by the absence of related symptoms. Written informed consent was obtained from all participants before enrollment. Variable: Demographic and clinical data were collected, including age, gender, education level, COVID-19 symptoms (e.g., cough, fever, dyspnea), duration since symptom onset, medical history, and smoking status. Taste function was qualitatively evaluated using the Waterless Empirical Taste Test (WETT ® ; Sensonics International, NJ, USA). This test consists of 27 strips with six different taste modalities: Sweet (sucrose), Sour (citric acid), Salty (NaCl), Bitter (Caffeine), and Umami (monosodium glutamate), with four different concentrations and ‘no taste’ as a negative control. Each strip was numbered, and participants were given a questionnaire to record their responses. After placing the monomer cellulose pad of the strip in their mouth for five to ten seconds, they were instructed to select the perceived taste from the options provided on the questionnaire[ 22 ]. The total WETT score was calculated as the sum of correct responses, ranging from 0 to 27. This test has demonstrated high validity and reliability with a test-retest reliability of 0.92 and a split-half reliability coefficient of 0.88. Smell function was assessed using the Pocket Smell Test (PST®; Sensonics International, NJ, USA), which includes eight microencapsulated odors embedded on brown pads. Participants were instructed to scratch and sniff each pad, then identify the perceived odor by choosing from multiple-choice options, even if they could not detect any smell. A correct response earned a score of 1, while incorrect answers were scored as 0. This test is widely utilized in clinical and epidemiological research and it classifies olfactory function into three levels: normosmia (total score of 7 or 8), microsmia (scores between 3 and 6), and anosmia (total score of 2 or less). It has demonstrated 89% sensitivity for distinguishing normosmia from olfactory dysfunction and 99% specificity for detecting anosmia[ 23 , 24 ]. Bias Control: To minimize selection bias, matched sampling was employed for healthy controls, ensuring age and gender comparability. Additionally, standardized testing protocols were followed to maintain consistency in taste and smell assessments. Statistical Analysis: The required sample size was determined using the following formula: n = [(Z α * √(2p(1-p)) + Z β * √(P 0 (1-P 0 ) + P 1 (1-P 1 )))]² / (P 1 - P 0 )² The parameters were set as follows: baseline prevalence in controls (P₀) = 0.05, expected prevalence in COVID-19 patients (P₁) = 0.30, pooled prevalence (p) = 0.17, significance level (α) = 0.05, power (1 − β) = 80%, critical value for Zα at α = 0.05: 1.96, and critical value for Zβ at β = 0.20: 0.85. Based on these assumptions, the minimum required sample size was 21 participants per group. To enhance the study's robustness and account for potential data loss, we included 30 participants in each group. Based on these assumptions, the minimum required sample size was 21 participants per group. However, to strengthen the study’s reliability and compensate for any potential data loss, the sample size was increased to 30 participants in each group. The normality of continuous variables was assessed using the Shapiro–Wilk test and Q-Q plots. A p-value greater than 0.05 indicated a normal distribution. Normally distributed numerical variables, including age, total WETT, and subdomain scores (sour, salty, sweet, bitter, and umami), were expressed as mean ± standard deviation (SD) and compared between groups using an independent samples t -test. Non-normally distributed variables, such as smell scores, were summarized as median and interquartile range (IQR) and compared using the Mann–Whitney U test. Categorical variables (e.g., gender) were presented as frequencies and percentages. Correlations between WETT scores, smell scores, age, and smoking status were evaluated using Spearman’s rank correlation coefficient. All statistical analyses were performed using Stata (Version 14, StataCorp LLC, College Station, TX, USA), and graphs and figures were generated using GraphPad Prism (Version 9.0, GraphPad Software, San Diego, CA, USA). A p-value of < 0.05 was considered statistically significant. Results A total of 30 patients with COVID-19 were included in this study, with a mean age of 39.20 years (SD = 14.74, range = 17–67), of whom 19 (63.3%) were male. The majority (83.3%) were non-smokers. One participant (3.3%) subjectively reported a history of smell dysfunction, and one (3.3%) had experienced both smell and taste dysfunction prior to COVID-19 (Table 1 .). The most common symptoms among COVID-19 patients were cough (66.7%), headache (60%), and fever (56.7%). Table 1 Demographic characteristics of participant. Variables COVID Patients (N = 30) Healthy Controls (N = 30) P -value Age , mean (SD) 39.20 (14.74) 38.50 (13.14) 0.87 Age, range 17 to 67 18 to 68 - Gender n (%) Female: 11 (36.7%) Male: 19 (63.3%) Female: 11 (36.7%) Male: 19 (63.3%) 1.00 Smoking history , n (%) Current smoker: 5 (16.67%) Non-smoker: 25 (83.33%) Current smoker: 5 (16.67%) Non-smoker: 25 (83.33%) 1.00 Chemosensory complaint , n (%) None = 28 Smell dysfunction: 1 (3.33%) Taste dysfunction: 0 Taste and smell dysfunction: 1 (3.33%) None = 28 Smell dysfunction: 1 (3.33%) Taste dysfunction: 0 Taste and smell dysfunction: 2 (6.367%) 0.83 Abbreviations: COVID-19: Coronavirus Disease 2019, SD: Standard Deviation The healthy control group consisted of 30 sex- and age-matched individuals with a mean age of 38.50 (SD = 13.14, range = 18–68). Among them, 19 (63.3%) were male. About 83% were non-smokers. One participant (3.3%) experienced a history of smell dysfunction, and two (6.7%) reported both prior smell and taste dysfunction prior to the study (Table 1 ). The mean WETT score was 16.14 (SD = 4.06) in the COVID-19 group and 18.73 (SD = 5.06) in the control group, demonstrating a statistically significant difference between the two groups (p-value < 0.05, Fig. 1 . A ). Among taste subdomains, sour, bitter, and umami scores were significantly lower in COVID-19 patients compared to healthy controls (Table 2 , Fig. 2 ). However, no significant differences were observed in the sweet, salty, and no taste subdomains. Table 2 Comparison of Smell and Taste Function Between COVID-19 Patients and Healthy Controls COVID Patients N = 30 Healthy Controls N = 30 P -value WETT score , mean (SD) 16.14 (4.06) 18.73 (5.06) 0.03 Sweet 2.47 (0.25) 2.63 (0.18) 0.98 Sour 2.40 (0.22) 3.27 (0.19) 0.003* Salty 2.60 (0.25) 3.20 (0.16) 0.11 Bitter 1.83 (0.25) 2.70 (0.21) 0.016* Umami 0.63 (0.19) 1.53 (0.26) 0.012* No taste 5.23 (0.3) 5.40 (0.33) 0.97 Mean smell score , median, IQR 6 (5–7) 7 (6–8) 0.002* The median smell scores were significantly lower in COVID patients (median = 6, IQR = 5–7) compared to healthy controls (median = 7, IQR = 6–8) (p-value < 0.05) (Fig. 1 . B ). Among COVID-19 patients, 10% presented anosmia, 56.7% exhibited microsomia, and 33.3% presented normosmia. In the control group, 70 percent had normosmia, with only one participant presenting anosmia (Table 3 ). Table 3 Distribution of different levels of smell dysfunction in both patient and control groups. Level of smell dysfunction COVID-19 Patients N (%) Healthy controls N (%) Normosmia (score > 6) 10 (33.3%) 21 (70%) Microsmia (score = 3–6) 17 (56.7%) 8 (26.7%) Anosmia (score < 3) 3 (10%) 1 (3.3%) Although the trend was lower in WETT score among smokers, the difference between current and non-smokers was not statistically significant within either patient or control groups (Table 4 ). However, considering all participants, the WETT score is significantly lower in current smokers compared to non-smokers (p-value < 0.05). Table 4 Comparison of Smell and Taste Function by Smoking Status in COVID-19 Patients and Healthy Controls Current smoker Non-smoker Chemosensory function COVID-19 patients (n = 5) Healthy controls (n = 5) Total (n = 10) COVID-19 patients (n = 25) Healthy controls (n = 25) Total (n = 25) WETT score 13 (12 to15) 14 (9 to 24) 13.5 (9 to 16) 16 (15 to 18) 20 (16 to 22) 18 (15 to 21) Smell score 6 (5 to 6) 6 (6 to 8) 6 (5 to 7) 6 (4 to 7) 7 (7 to 8) 7 (6 to 8) No significant correlation was observed between smell and taste scores in COVID-19 patients (Spearman’s r = 0.22, p-value > 0.05). However, in the control group, a moderate positive correlation was found between smell and taste scores (Spearman’s r = 0.36, p < 0.05) (Fig. 3 ). The odds of having smell dysfunction were 4.67 times higher in COVID-19 patients compared to healthy controls (OR = 4.67, 95% CI: 1.57–13.87, p-value < 0.05). However, considering the small sample size and the wide confidence interval, this finding should be interpreted cautiously. Among COVID-19 patients, both smell and taste scores tended to improve with increasing time since symptom onset (Fig. 4 ). However, the taste scores were not significantly correlated with symptom duration (Spearman’s r = -0.18, p-value > 0.05), while a weak correlation existed between smell scores and symptom duration (Spearman’s r = 0.15, p-value < 0.05). Age showed a significant negative correlation with WETT scores in both groups (COVID-19: Spearman’s r = -0.39, p-value < 0.05; Controls: Spearman’s r = -0.62, p-value < 0.05). Similarly, in the COVID-19 group, higher age was associated with lower smell scores (Spearman’s ρ =-0.24, p 0.05). There was no significant association between taste and smell function and gender in either of the groups. Discussion This prospective, cross-sectional study employed validated, objective measures to assess taste (WETT) and smell function in patients recently diagnosed with COVID-19 and matched healthy controls. Our primary findings reveal statistically significant impairments in both gustatory and olfactory function among individuals in the COVID-19 group compared to their healthy counterparts during the study period from February to March 2022. Gustatory Dysfunction: A key finding of this study is the objective demonstration of impaired taste function in the COVID-19 cohort, as shown by significantly lower mean total WETT scores compared to controls. A pooled analysis on 817 patients with COVID-19 demonstrated that almost fifty percent of patients experienced altered taste sensation [ 25 ]. The studies incorporating objective taste tests are limited. Sharetts et al. used the same WETT tool among one-year post-COVID patients and healthy controls, and they found no significant difference in taste scores between the two groups [ 26 ]. Similarly, Chiang and Jiang reported a relatively low rate of hypogeusia, reported as 17% in their long-COVID sample, but their mean WETT score (mean = 24) was higher than the score in our control group (mean = 18.73), suggesting differences in baseline function or assessment timing [ 27 ]. These discrepancies suggest that gustatory dysfunction may be more noticeable or prevalent during the acute/subacute stages of COVID-19, as captured in our study, and that it likely improves over time for many individuals. There are still limited studies using objective taste tests during the acute phase, making our findings especially relevant. Interestingly, our data showed no correlation between symptom onset and taste function within the acute phase. This aligns with previous reports that while many patients recover taste relatively quickly, others experience persistent dysfunction. Moreover, some studies suggest gustatory is variable between different genders. Our study demonstrated no correlation between gender and WETT scores, which is consistent with the result of a meta-analysis assessing the risk factors for olfactory and gustatory dysfunction in patients with COVID-19 [ 10 ]. On the other hand, we demonstrated that the taste score was negatively correlated with participants’ age in either the patient or the control group, which is relevant to other studies[ 28 ]. Our findings support the idea that taste loss is not just a subjective complaint but a real, measurable symptom in early COVID-19, which can occur independently of smell loss. This is suggestive of a distinct pathophysiological mechanism. This divergence has also been observed in other studies using quantitative tools[ 29 ]. Regarding individual taste qualities, we found that sour, bitter, and umami scores were significantly lower in the COVID-19 group. This is in line with Minichetti et al., who indicated that patients mostly self-reported deficits in sour, bitter, and umami. They also demonstrated in a three-year follow-up, patients with persistent chemosensory dysfunction had lower scores in sweet, sour, bitter, and umami tastes using the Brief Waterless taste test (BWETT) [ 30 ]. Asadi reported hypersensitivity to salt in COVID-19 patients, while the sensitivity to sweet, sour, and umami was reduced [ 31 ]. On the other hand, Cao et al. found no taste differences among recently infected healthcare workers using the Brief Self-Administered Waterless Empirical Taste Test [ 32 ], while Sharetts et al. also reported normal taste scores post-COVID. In contrast, Vaira et al. reported hypogeusia in over 60% of patients using the Taste Strips Test, especially for bitter and sour [ 29 ]. These varying findings may reflect differences in study timing, populations, or methods of taste assessment. Pro-inflammatory cytokines may selectively affect the perception of certain taste qualities. Supporting this, Patel et al. reported lower salivary levels of taste-related proteins like Sonic Hedgehog and Gustin in long-COVID patients, correlating with bitter taste impairment even when total WETT scores were normal [ 17 ]. Beyond cellular mechanisms, the oral and tongue microbiome may also play a role in the etiology of gustatory dysfunction. COVID-19 has been associated with reduced microbial diversity and an increased abundance of pro-inflammatory bacteria such as Prevotella and Fusobacterium. These changes can disrupt immune balance around the taste buds and trigger local inflammation. Recent studies suggest that shifts in the lingual microbiome can influence taste perception through both immune and metabolic pathways [ 33 ]. The microbiome may act as both a mediator of dysfunction and a possible therapeutic target, and its therapeutic potential can be investigated in future studies. Taken together, the literature highlights a multifactorial basis for gustatory deficits in COVID-19, involving direct viral damage, immune-mediated suppression of taste cell renewal, altered salivary protein composition, and microbiome dysbiosis [ 33 ]. Olfactory Dysfunction: Consistent with a large body of literature, our study confirmed significant olfactory impairment in the COVID-19 group. Patients exhibited significantly lower median smell scores (6 vs. 7, p = 0.002) and a markedly different distribution of function, with substantially higher rates of objectively identified microsmia (56.7% vs. 26.7%) and anosmia (10% vs. 3.3%) compared to controls. Overall, 66.7% of COVID-19 patients had measurable olfactory impairment, and the odds of smell dysfunction were over four times higher in this group (OR = 4.67). It aligns with the findings of Hannum et al., who reported a pooled prevalence of 77% for objectively measured olfactory loss, significantly higher than estimates based on patient self-reporting[ 18 ]. This discrepancy between subjective and objective data underscores the importance of using standardized smell tests to capture the true burden of dysfunction, which may otherwise go unrecognized. Notably, olfactory impairment was associated with age in COVID-19 patients and it was not related to the smoking status of patients. These findings align with a meta-analysis study on risk factors of olfactory dysfunction [ 10 ]. However, according to previous reports, female gender and smoking are predictive of persistent olfactory loss among demographic characteristics[ 9 , 30 ]. The SARS-CoV-2 variants are another factor affecting the incidence of chemosensory dysfunction, as the Omicron variant is associated with a lower rate of olfactory dysfunction compared to the alpha or delta variants [ 34 ]. Our results regarding olfactory impairment are consistent with the long-term findings of both Sharetts et al. and Chiang & Jiang, who also reported significantly lower UPSIT scores and persistent olfactory dysfunction in individuals with a history of COVID-19, even months to a year post-infection [ 26 , 27 ]. Similarly, Moein et al. found that one-third of patients continued to experience smell impairment up to 10 weeks post-onset[ 5 ]. This collective evidence suggests that while taste function may recover more readily for many, olfactory dysfunction is often a more persistent sequela of the infection. While we observed a weak positive correlation between olfactory scores and symptom duration, suggesting some potential for recovery within our study timeframe, longer follow-up would be necessary to confirm sustained improvement. Some studies have indicated that chemosensory dysfunction might be associated with low severity of COVID-19[ 35 ], although our study was not designed to assess this correlation. Histopathologic changes, such as squamous metaplasia and replacement of the OE with respiratory-type epithelium, mirror those seen in chronic rhinosinusitis and may compromise the OE’s ability to regenerate. At the same time, local immune activation, particularly involving macrophages and dendritic cells, can create a chronic inflammatory microenvironment that suppresses neurogenic signaling pathways, including Wnt, Notch, and NF-κB, further restricting recovery [ 36 ]. Neuroimaging studies have revealed that COVID-19-related anosmia is associated with structural changes and volume loss in limbic and memory-related brain regions such as the hippocampus, amygdala, and orbitofrontal cortex. Such findings are concerning, as they are similar to the patterns seen in neurodegenerative diseases like Alzheimer’s and may reflect accelerated brain aging [ 37 ]. These findings highlight the importance of following patients over time to better understand whether the brain changes seen in those with COVID-19-related smell loss might increase their risk for developing memory problems or neurodegenerative diseases later in life. Therapeutic implication: About 5% of people with chemosensory loss following COVID-19 had sustained olfactory or taste dysfunction six months later [ 9 ]. Given the prevalence and impact of chemosensory dysfunction, various interventions have been proposed. Olfactory training, involving repeated exposure to a set of odors over time, remains the most evidence-based approach for post-viral olfactory loss and may also benefit COVID-19-related anosmia [ 38 ]. A narrative review indicated that COVID-19 leads to a chronic inflammatory state, and the level of inflammatory cytokines such as IL-4 and IL-6 is still upregulated. Therefore, many immunomodulatory interventions have been applied in this condition, including local corticosteroids and Platelet-Rich Plasma (PRP) [ 39 , 40 ]. For taste disorders, few specific treatments exist. Zinc supplementation has shown modest benefit in select viral etiologies, though evidence in COVID-19 remains limited [ 27 ]. Ongoing research into neuroprotective and anti-inflammatory agents can be considered as therapeutic agents for managing persistent sensory loss. This study possesses several limitations. Firstly, the cross-sectional nature of this study limits the ability to assess the progression or recovery of olfactory and gustatory dysfunction over time. Longitudinal studies are needed to evaluate the persistence or resolution of sensory deficits. Secondly, Participants were recruited from a specific geographic and clinical setting in Iran, which may limit the generalizability of findings. Third, the sample size may limit the power to detect smaller but clinically meaningful differences or to perform subgroup analyses. Another limitation is the lack of assessment of inflammatory biomarkers, which could help clarify the biological mechanisms underlying the observed dysfunctions. Conclusion In conclusion, this study provides objective evidence for significant impairment of both taste and smell function in patients assessed over the early phase of COVID-19 diagnosis compared to matched controls. The acute phase gustatory dysfunction suggests that taste dysfunction should be recognized as an important and measurable symptom of COVID-19, with implications for both clinical screening and understanding long-term recovery trajectories. The PST olfactory findings align with extensive literature demonstrating frequent smell loss following COVID-19 infection. These results highlight the distinct impacts of SARS-CoV-2 on both chemosensory systems and reinforce the critical importance of employing objective testing methodologies in evaluating these symptoms. Declarations Conflict of Interest: Richard L. Doty received consulting fees from Johnson & Johnson and Merck, and royalty payments from Cambridge University Press, Elsevier, Johns Hopkins University Press, McGraw-Hill, and John Wiley & Sons outside the submitted work. He is president and major shareholder of Sensonics International, the manufacturer of the taste test used in this study. The remaining authors declare no conflicts of interest. Authors’ contributions: EK contributed to the study design, data collection, data analysis, and drafting the manuscript. STM was involved in conceptualization and study design, provided administrative support, contributed to data collection and interpretation, participated in drafting and revising the manuscript, and supervised the project. AHD contributed to drafting the manuscript. HRB participated in conceptualization, study design, data interpretation, and manuscript revision. RLD contributed to conceptualization and study design, supervised the project, and approved the final version of the manuscript. Funding: No funding is received from any funding parties. Ethical declarations : This study was reviewed and approved by the Research Ethics Committee of Iran University of Medical Sciences with the reference number of IR.IUMS.FMD.REC.1400.598. This project was conducted in accordance with the latest version of the Helsinki Declaration. Data Availability: The datasets are available from the corresponding author upon reasonable request. Acknowledgment: The Authors would like to express their gratitude to their fellow colleagues in Iran University of Medical Sciences, the Institute for Research in Fundamental Sciences, and Sensonics International for their support and contribution. References Alves, L.S.M., et al., Changes in taste perception in elderly population and its potential impact on oral health: a systematic review with meta-analysis. Frontiers in Oral Health, 2024. 5 : p. 1517913. Maniaci, A., et al., Taste and smell disorders: a critical look at olfactory and gustatory dysfunction . 2024, MDPI. p. 301. Xydakis, M.S., et al., Smell and taste dysfunction in patients with COVID-19. The Lancet Infectious Diseases, 2020. 20 (9): p. 1015-1016. 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A prospective study using psychophysical testing . in International Forum of Allergy & Rhinology . 2021. Soter, A., et al., Accuracy of self‐report in detecting taste dysfunction. The Laryngoscope, 2008. 118 (4): p. 611-617. Von Elm, E., et al., The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. The lancet, 2007. 370 (9596): p. 1453-1457. Doty, R.L., C. Wylie, and M. Potter, Validation of the waterless empirical taste test (WETT®). Behavior research methods, 2021. 53 : p. 864-873. On, A., et al., The 8-item NHANES pocket smell test®: Normative data. Applied Neuropsychology: Adult, 2023: p. 1-6. Moein, S.T., et al., Development of parallel forms of a brief smell identification test useful for longitudinal testing. Behavior Research Methods, 2024. 56 (3): p. 1449-1458. Aziz, M., et al., Taste changes (dysgeusia) in COVID-19: a systematic review and meta-analysis. Gastroenterology, 2020. 159 (3): p. 1132-1133. Sharetts, R., et al., Long-term taste and smell outcomes after COVID-19. JAMA Network Open, 2024. 7 (4): p. e247818-e247818. Chiang, Y.-F. and R.-S. Jiang, Effect of oral zinc and steroids on long COVID hyposmia and hypogeusia. SAGE Open Medicine, 2024. 12 : p. 20503121241301894. Doty, R.L., R. Sharetts, and S.T. Moein. Self‐Administered Taste Testing Without Water: Normative Data for the 53‐Item Waterless Empirical Taste Test (WETT) . in International Forum of Allergy & Rhinology . 2025. Wiley Online Library. Vaira, L.A., et al., Objective evaluation of anosmia and ageusia in COVID‐19 patients: single‐center experience on 72 cases. Head & neck, 2020. 42 (6): p. 1252-1258. Minichetti, D.G., et al., Determinants of persistence and recovery of chronic coronavirus disease 2019 chemosensory dysfunction. Journal of Allergy and Clinical Immunology, 2025. 155 (1): p. 120-134. Asadi, M.M., et al., Quantitative analysis of taste disorder in COVID-19 patients, the hypersensitivity to salty quality. New microbes and new infections, 2021. 43 : p. 100919. Cao, A.C., et al., Objective screening for olfactory and gustatory dysfunction during the COVID-19 pandemic: a prospective study in healthcare workers using self-administered testing. World Journal of Otorhinolaryngology-Head and Neck Surgery, 2022. 8 (03): p. 249-256. Srinivasan, M., Taste dysfunction and long COVID-19. Frontiers in cellular and infection microbiology, 2021. 11 : p. 716563. von Bartheld, C.S. and L. Wang, Prevalence of olfactory dysfunction with the omicron variant of SARS-CoV-2: a systematic review and meta-analysis. Cells, 2023. 12 (3): p. 430. Meunier, N., et al., COVID 19-induced smell and taste impairments: putative impact on physiology. Frontiers in physiology, 2021. 11 : p. 625110. Xie, Y., et al., Aging and chronic inflammation: impacts on olfactory dysfunction-a comprehensive review. Cellular and Molecular Life Sciences, 2025. 82 (1): p. 199. Leon, M., E.T. Troscianko, and C.C. Woo, Inflammation and olfactory loss are associated with at least 139 medical conditions. Frontiers in Molecular Neuroscience, 2024. 17 : p. 1455418. Ojha, P. and A. Dixit, Olfactory training for olfactory dysfunction in COVID‐19: A promising mitigation amidst looming neurocognitive sequelae of the pandemic. Clinical and Experimental Pharmacology and Physiology, 2022. 49 (4): p. 462-473. Yan, C.H., et al. Use of platelet‐rich plasma for COVID‐19–related olfactory loss: a randomized controlled trial . in International Forum of Allergy & Rhinology . 2023. Wiley Online Library. Steffens, Y., et al., Effectiveness and safety of PRP on persistent olfactory dysfunction related to COVID-19. European Archives of Oto-Rhino-Laryngology, 2022. 279 (12): p. 5951-5953. Additional Declarations Competing interest reported. Richard L. Doty received consulting fees from Johnson & Johnson and Merck, and royalty payments from Cambridge University Press, Elsevier, Johns Hopkins University Press, McGraw-Hill, and John Wiley & Sons outside the submitted work. He is president and major shareholder of Sensonics International, the manufacturer of the taste test used in this study. The remaining authors declare no conflicts of interest. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7917937","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":542174566,"identity":"835b9389-0c93-40d1-bf27-397dc5bd02fc","order_by":0,"name":"Elaheh Khodadoust","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Elaheh","middleName":"","lastName":"Khodadoust","suffix":""},{"id":542174568,"identity":"ec3f17b6-4af7-4176-ac5d-b20f43bd8037","order_by":1,"name":"Shima T. Moein","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYDACCRBRwJDAwN4AZBhYEKWFsYHBAKiF5wBIiwQpWiQS4JbiB/KzG9gf/DCwyTO4+fzqhh8FEgz87d0JeLUY3DnA2NhjkFZscDun7GYP0GESZ85uwK9FIoGxgcfgcOKG2zlpN3iAWgwkcvFrkZ+RwNj4x+B/4oabZ9Ju/iFGC8ONBMZmHoMDiRtusB+7TZQtBjcSG2fLGCQnzjyTw3ZbxkCCh6Bf5GckH/j4psIuse/48Wc33/yxkeNv7yXgMFC0gIDCAR4DEM1DQDmydQ3sD4hXPQpGwSgYBSMKAAB6dUz1QFDZCAAAAABJRU5ErkJggg==","orcid":"","institution":"Sensonics International","correspondingAuthor":true,"prefix":"","firstName":"Shima","middleName":"T.","lastName":"Moein","suffix":""},{"id":542174570,"identity":"a565dee4-7639-44f0-adf8-fd953fe369b0","order_by":2,"name":"Amir H. Dehqan","email":"","orcid":"","institution":"Institute for Research in Fundamental Sciences (IPM)","correspondingAuthor":false,"prefix":"","firstName":"Amir","middleName":"H.","lastName":"Dehqan","suffix":""},{"id":542174573,"identity":"cb5ab0fe-43cd-4b0d-84bb-d458040e534f","order_by":3,"name":"Hamid Reza Baradaran","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Hamid","middleName":"Reza","lastName":"Baradaran","suffix":""},{"id":542174575,"identity":"490737a2-aa46-40f2-87e8-de8f8c8e3152","order_by":4,"name":"Richard L. 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16:38:19","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":97966,"visible":true,"origin":"","legend":"","description":"","filename":"108294cb4f1e4b659a8752782ff1a69d1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7917937/v1/b638a4d2241219f3992690b4.xml"},{"id":95797936,"identity":"da84fa83-8e48-471b-b434-cd24925d7fa4","added_by":"auto","created_at":"2025-11-13 08:12:52","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":109925,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7917937/v1/734f614b9b0edab36dae9008.html"},{"id":95662796,"identity":"76a08d42-b264-48c2-829b-f26c8c710076","added_by":"auto","created_at":"2025-11-11 16:38:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1995885,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of chemosensory dysfunction between COVID-19 patients and healthy controls. A. \u003c/strong\u003eViolin plot of the WETT scores indicating gustatory function in patients and controls. \u003cstrong\u003eB.\u003c/strong\u003e Violin plot of the PST scores indicating olfactory function in the same groups. Each violin plot shows the kernel density distribution, with horizontal lines representing the median and the 25\u003csup\u003eth\u003c/sup\u003e-75\u003csup\u003eth\u003c/sup\u003e interquartile range.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7917937/v1/0e80cc7f0db34c056ffec64d.jpg"},{"id":95662803,"identity":"24f76a81-e5a8-4cb2-990c-70f28c2d3ff1","added_by":"auto","created_at":"2025-11-11 16:38:10","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":816885,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of specific taste qualities between COVID-19 patients and healthy controls.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe distribution of scores for specific taste modalities assessed by the Waterless Empirical Taste Test (WETT): (A) sweet, (B) sour, (C) salty, (D) bitter, (E) umami, and (F) no-taste (blanks). Triangles represent patient scores, and circles represent control scores; bars indicate Median ± IQR. *:\u003cem\u003eP\u003c/em\u003e_value \u0026lt;0.05, **: \u003cem\u003eP\u003c/em\u003e_value\u0026lt;0.01, ns: non-significant\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7917937/v1/e049a2b2a1625181414cc750.jpg"},{"id":95662894,"identity":"fa53dbd3-76e5-46f2-b421-76a30662bfd3","added_by":"auto","created_at":"2025-11-11 16:38:17","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":230674,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCorrelation between objective taste and smell scores in COVID-19 patients and healthy controls.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7917937/v1/c3ccb4ce3263d6789de76b51.jpg"},{"id":95663155,"identity":"be63553c-c578-4e81-9251-e5c813b0749e","added_by":"auto","created_at":"2025-11-11 16:38:26","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2102215,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of gustatory and olfactory function according to symptom duration in COVID-19 patients.\u003c/strong\u003e (A) mean WETT scores with standard deviation (SD) error bars, (B) median smell scores with interquartile range (IQR) error bars across four symptom duration groups (1–4 days, 5–8 days, 8–14 days, and \u0026gt;14 days).\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7917937/v1/23f6ad20d9f9081a57185d94.jpg"},{"id":96248411,"identity":"4b20f507-6e4e-4148-aeb7-dd80c9a3ebb5","added_by":"auto","created_at":"2025-11-19 07:28:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5462571,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7917937/v1/bbb88e3e-b128-4c98-9eb4-8d054d8b6858.pdf"}],"financialInterests":"Competing interest reported. Richard L. Doty received consulting fees from Johnson \u0026 Johnson and Merck, and royalty payments from Cambridge University Press, Elsevier, Johns Hopkins University Press, McGraw-Hill, and John Wiley \u0026 Sons outside the submitted work. He is president and major shareholder of Sensonics International, the manufacturer of the taste test used in this study. The remaining authors declare no conflicts of interest.","formattedTitle":"A Comparative Evaluation of Taste and Smell Dysfunction in COVID-19: A Cross-sectional Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTaste and smell are essential chemical senses that play a crucial role in nutrition, safety, and overall well-being and they are tied to memory, emotion, and social behaviours [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Dysfunction in these systems can lead to nutritional imbalances, increased risk from environmental hazards, and significant impacts on mental health and quality of life [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The Coronavirus Disease (COVID-19) pandemic brought unprecedented global attention to chemosensory changes as one of the early symptoms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection often occurs even in mild or asymptomatic cases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This chemosensory loss presents as anosmia/hyposmia or agusia/hypogusia, distinguishes COVID-19 from many other respiratory viruses, and can sometimes present as the sole clinical manifestation [\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Chemosensory loss contributes to the burden of COVID-19 by affecting individuals\u0026rsquo; quality of life, interpersonal interaction, mental health, and safety [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Additionally, chemosensory symptoms, while often considered minor, may carry broader neurological implications due to their anatomical pathway, projecting directly to limbic and memory-related brain regions such as the hippocampus, amygdala, and orbitofrontal cortex [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWhile the exact mechanisms are still under investigation, current evidence points to multiple pathways. The mechanisms behind gustatory dysfunction in COVID-19 are likely multifactorial. Experimental studies have confirmed that SARS-CoV-2 can directly infect and replicate in taste bud cells, further supporting a biological basis for the observed taste loss in COVID-19. On a cellular level, Type II taste receptor cells, which detect sweet, bitter, and umami, express ACE2, making them direct targets for viral entry [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These cells are also responsive to inflammation via Toll-like receptors and downstream NF-κB signaling, which can impair their lifespan and renewal.\u003c/p\u003e\u003cp\u003eThe underlying pathophysiology of COVID-19-related smell loss appears to involve both direct and indirect mechanisms within the olfactory epithelium (OE). SARS-CoV-2 primarily targets sustentacular (SUS) cells, which express ACE2 and TMPRSS2, rather than the olfactory sensory neurons (OSNs) themselves [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Infection of these support cells leads to epithelial disorganization, inflammatory infiltration, and disrupted neuronal function [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Neuro-inflammation, invasion of the virus to the Central Nervous System (CNS) and damage to the olfactory and trigeminal nerve, which leads to olfactory and gustatory dysfunction. Nasal symptoms such as nasal congestion, can be a reason for olfactory dysfunction[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, the viral infection and inflammation reduce the progenitor cell renewal, while they increase taste cell death [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe reported prevalence of COVID-19-associated chemosensory dysfunction varies widely across studies from 5% to over 98% for smell and 6% to 93% for taste dysfunction, influenced by factors such as the viral variant, population demographics, disease severity, and importantly, the method of assessment. Self-reported symptoms, while easy to collect, are known to be unreliable. A Systematic reviews and meta-analysis study has demonstrated that objective direct testing methods reveal significantly higher prevalence rates of olfactory loss compared to subjective self-reports, highlighting the critical need for standardized, validated measures in research and clinical assessment [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Taste loss has often been misinterpreted as smell loss, and it was indicated that self-reported taste scores are better correlated with olfactory scores, rather than gustatory function [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].. The sensitivity and specificity of the self-report measures in assessing taste dysfunction in patients with COVID-19 are reported to be low [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eImportantly, while some studies have applied objective tools to assess long-term outcomes of chemosensory dysfunction, very few have focused on the acute or subacute phases of COVID-19, particularly in non-Western populations. A meta-analysis on taste loss following COVID-19 reported that among 138,897 individuals diagnosed with COVID-19, only 257 were evaluated using standardized objective taste tests[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Studies examining different taste qualities, such as sweet, salty, sour, bitter, and umami, are especially limited.\u003c/p\u003e\u003cp\u003eTo address these gaps, the present study aimed to objectively evaluate gustatory and olfactory functions using validated tools in recently diagnosed COVID-19 patients compared with a well-matched healthy control group within an Iranian population.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and setting:\u003c/h2\u003e\u003cp\u003eThis prospective, analytical, cross-sectional study was conducted between February and March 2022 in tertiary hospitals affiliated with Iran University of Medical Sciences, Tehran, Iran, in collaboration with the Institute for Research in Fundamental Sciences, Tehran, Iran. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The Ethics Committee of Iran University of Medical Sciences approved this study with the reference number IR.IUMS.FMD.REC.1400.598, and it was conducted in accordance with the latest version of the Helsinki Declaration.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eParticipants:\u003c/h3\u003e\n\u003cp\u003ePatients with confirmed COVID-19 and healthy controls were enrolled using a combination of consecutive sampling for cases and matched sampling for controls. Eligible participants who provided written informed consent were included in the study.\u003c/p\u003e\u003cp\u003eThe inclusion criteria for the patient group involve adults aged 17 to 70 years with a positive Real-Time reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 from nasopharyngeal swab samples. The exclusion criteria involve pregnancy, chronic sinusitis, and a history of traumatic head injury.\u003c/p\u003e\u003cp\u003ePatients with COVID-19 confirmed with RT-PCR who fulfilled eligibility criteria were enrolled consecutively from Firoozgar Hospital and Rasool Akram Hospital between February and March 2022. Inclusion criteria required patients aged between 18 and 70 years. Individuals were excluded if they were pregnant or had a history of chronic sinusitis, traumatic head injury, or any other physiological or structural condition affecting taste or smell. COVID-19 patients meeting the eligibility criteria were recruited consecutively from the infectious disease wards of Firoozgar and Rasool Akram Hospitals during the study period.\u003c/p\u003e\u003cp\u003eHealthy controls were selected from the general population and matched to patients based on age and gender. They had no history of respiratory tract infections in the past three months, as confirmed by the absence of related symptoms. Written informed consent was obtained from all participants before enrollment.\u003c/p\u003e\n\u003ch3\u003eVariable:\u003c/h3\u003e\n\u003cp\u003eDemographic and clinical data were collected, including age, gender, education level, COVID-19 symptoms (e.g., cough, fever, dyspnea), duration since symptom onset, medical history, and smoking status.\u003c/p\u003e\u003cp\u003eTaste function was qualitatively evaluated using the Waterless Empirical Taste Test (WETT\u003csup\u003e\u0026reg;\u003c/sup\u003e; Sensonics International, NJ, USA). This test consists of 27 strips with six different taste modalities: Sweet (sucrose), Sour (citric acid), Salty (NaCl), Bitter (Caffeine), and Umami (monosodium glutamate), with four different concentrations and \u0026lsquo;no taste\u0026rsquo; as a negative control. Each strip was numbered, and participants were given a questionnaire to record their responses. After placing the monomer cellulose pad of the strip in their mouth for five to ten seconds, they were instructed to select the perceived taste from the options provided on the questionnaire[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The total WETT score was calculated as the sum of correct responses, ranging from 0 to 27. This test has demonstrated high validity and reliability with a test-retest reliability of 0.92 and a split-half reliability coefficient of 0.88.\u003c/p\u003e\u003cp\u003eSmell function was assessed using the Pocket Smell Test (PST\u0026reg;; Sensonics International, NJ, USA), which includes eight microencapsulated odors embedded on brown pads. Participants were instructed to scratch and sniff each pad, then identify the perceived odor by choosing from multiple-choice options, even if they could not detect any smell. A correct response earned a score of 1, while incorrect answers were scored as 0. This test is widely utilized in clinical and epidemiological research and it classifies olfactory function into three levels: normosmia (total score of 7 or 8), microsmia (scores between 3 and 6), and anosmia (total score of 2 or less). It has demonstrated 89% sensitivity for distinguishing normosmia from olfactory dysfunction and 99% specificity for detecting anosmia[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eBias Control:\u003c/h3\u003e\n\u003cp\u003eTo minimize selection bias, matched sampling was employed for healthy controls, ensuring age and gender comparability. Additionally, standardized testing protocols were followed to maintain consistency in taste and smell assessments.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis:\u003c/h2\u003e\u003cp\u003eThe required sample size was determined using the following formula:\u003c/p\u003e\u003cp\u003e\u003cem\u003en\u003c/em\u003e = [(Z\u003csub\u003eα\u003c/sub\u003e * \u0026radic;(2p(1-p))\u0026thinsp;+\u0026thinsp;Z\u003csub\u003eβ\u003c/sub\u003e * \u0026radic;(P\u003csub\u003e0\u003c/sub\u003e(1-P\u003csub\u003e0\u003c/sub\u003e)\u0026thinsp;+\u0026thinsp;P\u003csub\u003e1\u003c/sub\u003e(1-P\u003csub\u003e1\u003c/sub\u003e)))]\u0026sup2; / (P\u003csub\u003e1\u003c/sub\u003e - P\u003csub\u003e0\u003c/sub\u003e)\u0026sup2;\u003c/p\u003e\u003cp\u003eThe parameters were set as follows: baseline prevalence in controls (P₀)\u0026thinsp;=\u0026thinsp;0.05, expected prevalence in COVID-19 patients (P₁)\u0026thinsp;=\u0026thinsp;0.30, pooled prevalence (p)\u0026thinsp;=\u0026thinsp;0.17, significance level (α)\u0026thinsp;=\u0026thinsp;0.05, power (1\u0026thinsp;\u0026minus;\u0026thinsp;β)\u0026thinsp;=\u0026thinsp;80%, critical value for Zα at α\u0026thinsp;=\u0026thinsp;0.05: 1.96, and critical value for Zβ at β\u0026thinsp;=\u0026thinsp;0.20: 0.85. Based on these assumptions, the minimum required sample size was 21 participants per group. To enhance the study's robustness and account for potential data loss, we included 30 participants in each group.\u003c/p\u003e\u003cp\u003eBased on these assumptions, the minimum required sample size was 21 participants per group. However, to strengthen the study\u0026rsquo;s reliability and compensate for any potential data loss, the sample size was increased to 30 participants in each group.\u003c/p\u003e\u003cp\u003eThe normality of continuous variables was assessed using the Shapiro\u0026ndash;Wilk test and Q-Q plots. A p-value greater than 0.05 indicated a normal distribution. Normally distributed numerical variables, including age, total WETT, and subdomain scores (sour, salty, sweet, bitter, and umami), were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and compared between groups using an independent samples \u003cem\u003et\u003c/em\u003e-test. Non-normally distributed variables, such as smell scores, were summarized as median and interquartile range (IQR) and compared using the Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test. Categorical variables (e.g., gender) were presented as frequencies and percentages. Correlations between WETT scores, smell scores, age, and smoking status were evaluated using Spearman\u0026rsquo;s rank correlation coefficient.\u003c/p\u003e\u003cp\u003eAll statistical analyses were performed using Stata (Version 14, StataCorp LLC, College Station, TX, USA), and graphs and figures were generated using GraphPad Prism (Version 9.0, GraphPad Software, San Diego, CA, USA). A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 30 patients with COVID-19 were included in this study, with a mean age of 39.20 years (SD\u0026thinsp;=\u0026thinsp;14.74, range\u0026thinsp;=\u0026thinsp;17\u0026ndash;67), of whom 19 (63.3%) were male. The majority (83.3%) were non-smokers. One participant (3.3%) subjectively reported a history of smell dysfunction, and one (3.3%) had experienced both smell and taste dysfunction prior to COVID-19 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.). The most common symptoms among COVID-19 patients were cough (66.7%), headache (60%), and fever (56.7%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic characteristics of participant.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCOVID Patients\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHealthy Controls\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e, \u003cb\u003emean (SD)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39.20 (14.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.50 (13.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.87\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, range\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 to 67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 to 68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e \u003cb\u003en\u003c/b\u003e \u003cb\u003e(%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale: 11 (36.7%)\u003c/p\u003e\u003cp\u003eMale: 19 (63.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale: 11 (36.7%)\u003c/p\u003e\u003cp\u003eMale: 19 (63.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSmoking history\u003c/b\u003e, \u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCurrent smoker: 5 (16.67%)\u003c/p\u003e\u003cp\u003eNon-smoker: 25 (83.33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCurrent smoker: 5 (16.67%)\u003c/p\u003e\u003cp\u003eNon-smoker: 25 (83.33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChemosensory complaint\u003c/b\u003e, \u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNone\u0026thinsp;=\u0026thinsp;28\u003c/p\u003e\u003cp\u003eSmell dysfunction: 1 (3.33%)\u003c/p\u003e\u003cp\u003eTaste dysfunction: 0\u003c/p\u003e\u003cp\u003eTaste and smell dysfunction: 1 (3.33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNone\u0026thinsp;=\u0026thinsp;28\u003c/p\u003e\u003cp\u003eSmell dysfunction: 1 (3.33%)\u003c/p\u003e\u003cp\u003eTaste dysfunction: 0\u003c/p\u003e\u003cp\u003eTaste and smell dysfunction: 2 (6.367%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.83\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eAbbreviations: COVID-19: Coronavirus Disease 2019, SD: Standard Deviation\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe healthy control group consisted of 30 sex- and age-matched individuals with a mean age of 38.50 (SD\u0026thinsp;=\u0026thinsp;13.14, range\u0026thinsp;=\u0026thinsp;18\u0026ndash;68). Among them, 19 (63.3%) were male. About 83% were non-smokers. One participant (3.3%) experienced a history of smell dysfunction, and two (6.7%) reported both prior smell and taste dysfunction prior to the study (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe mean WETT score was 16.14 (SD\u0026thinsp;=\u0026thinsp;4.06) in the COVID-19 group and 18.73 (SD\u0026thinsp;=\u0026thinsp;5.06) in the control group, demonstrating a statistically significant difference between the two groups (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003cb\u003eA\u003c/b\u003e). Among taste subdomains, sour, bitter, and umami scores were significantly lower in COVID-19 patients compared to healthy controls (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, no significant differences were observed in the sweet, salty, and no taste subdomains.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of Smell and Taste Function Between COVID-19 Patients and Healthy Controls\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCOVID Patients\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHealthy Controls\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWETT score\u003c/b\u003e, \u003cb\u003emean (SD)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16.14 (4.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.73 (5.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSweet\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.47 (0.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.63 (0.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSour\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.40 (0.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.27 (0.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.003*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSalty\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.60 (0.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.20 (0.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBitter\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.83 (0.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.70 (0.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.016*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUmami\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.63 (0.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.53 (0.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.012*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNo taste\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.23 (0.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.40 (0.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean smell score\u003c/b\u003e, \u003cb\u003emedian, IQR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (6\u0026ndash;8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.002*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe median smell scores were significantly lower in COVID patients (median\u0026thinsp;=\u0026thinsp;6, IQR\u0026thinsp;=\u0026thinsp;5\u0026ndash;7) compared to healthy controls (median\u0026thinsp;=\u0026thinsp;7, IQR\u0026thinsp;=\u0026thinsp;6\u0026ndash;8) (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003cb\u003eB\u003c/b\u003e). Among COVID-19 patients, 10% presented anosmia, 56.7% exhibited microsomia, and 33.3% presented normosmia. In the control group, 70 percent had normosmia, with only one participant presenting anosmia (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDistribution of different levels of smell dysfunction in both patient and control groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLevel of smell dysfunction\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCOVID-19 Patients\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHealthy controls\u003c/p\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNormosmia (score\u0026thinsp;\u0026gt;\u0026thinsp;6)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (70%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMicrosmia (score\u0026thinsp;=\u0026thinsp;3\u0026ndash;6)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (56.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAnosmia (score\u0026thinsp;\u0026lt;\u0026thinsp;3)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAlthough the trend was lower in WETT score among smokers, the difference between current and non-smokers was not statistically significant within either patient or control groups (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). However, considering all participants, the WETT score is significantly lower in current smokers compared to non-smokers (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of Smell and Taste Function by Smoking Status in COVID-19 Patients and Healthy Controls\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eCurrent smoker\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eNon-smoker\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChemosensory function\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCOVID-19 patients\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHealthy controls\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCOVID-19 patients\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHealthy controls\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWETT score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (12 to15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (9 to 24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.5 (9 to 16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16 (15 to 18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e20 (16 to 22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18 (15 to 21)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSmell score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (5 to 6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (6 to 8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (5 to 7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6 (4 to 7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7 (7 to 8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7 (6 to 8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eNo significant correlation was observed between smell and taste scores in COVID-19 patients (Spearman\u0026rsquo;s r\u0026thinsp;=\u0026thinsp;0.22, p-value\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, in the control group, a moderate positive correlation was found between smell and taste scores (Spearman\u0026rsquo;s r\u0026thinsp;=\u0026thinsp;0.36, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The odds of having smell dysfunction were 4.67 times higher in COVID-19 patients compared to healthy controls (OR\u0026thinsp;=\u0026thinsp;4.67, 95% CI: 1.57\u0026ndash;13.87, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, considering the small sample size and the wide confidence interval, this finding should be interpreted cautiously.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAmong COVID-19 patients, both smell and taste scores tended to improve with increasing time since symptom onset (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). However, the taste scores were not significantly correlated with symptom duration (Spearman\u0026rsquo;s r = -0.18, p-value\u0026thinsp;\u0026gt;\u0026thinsp;0.05), while a weak correlation existed between smell scores and symptom duration (Spearman\u0026rsquo;s r\u0026thinsp;=\u0026thinsp;0.15, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAge showed a significant negative correlation with WETT scores in both groups (COVID-19: Spearman\u0026rsquo;s r = -0.39, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Controls: Spearman\u0026rsquo;s r = -0.62, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Similarly, in the COVID-19 group, higher age was associated with lower smell scores (Spearman\u0026rsquo;s ρ =-0.24, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), whereas no significant correlation was found between age and smell score among healthy controls (Spearman\u0026rsquo;s ρ = -0.24, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). There was no significant association between taste and smell function and gender in either of the groups.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective, cross-sectional study employed validated, objective measures to assess taste (WETT) and smell function in patients recently diagnosed with COVID-19 and matched healthy controls. Our primary findings reveal statistically significant impairments in both gustatory and olfactory function among individuals in the COVID-19 group compared to their healthy counterparts during the study period from February to March 2022.\u003c/p\u003e\n\u003ch3\u003eGustatory Dysfunction:\u003c/h3\u003e\n\u003cp\u003eA key finding of this study is the objective demonstration of impaired taste function in the COVID-19 cohort, as shown by significantly lower mean total WETT scores compared to controls. A pooled analysis on 817 patients with COVID-19 demonstrated that almost fifty percent of patients experienced altered taste sensation [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The studies incorporating objective taste tests are limited. Sharetts et al. used the same WETT tool among one-year post-COVID patients and healthy controls, and they found no significant difference in taste scores between the two groups [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Similarly, Chiang and Jiang reported a relatively low rate of hypogeusia, reported as 17% in their long-COVID sample, but their mean WETT score (mean\u0026thinsp;=\u0026thinsp;24) was higher than the score in our control group (mean\u0026thinsp;=\u0026thinsp;18.73), suggesting differences in baseline function or assessment timing [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. These discrepancies suggest that gustatory dysfunction may be more noticeable or prevalent during the acute/subacute stages of COVID-19, as captured in our study, and that it likely improves over time for many individuals. There are still limited studies using objective taste tests during the acute phase, making our findings especially relevant.\u003c/p\u003e\u003cp\u003eInterestingly, our data showed no correlation between symptom onset and taste function within the acute phase. This aligns with previous reports that while many patients recover taste relatively quickly, others experience persistent dysfunction. Moreover, some studies suggest gustatory is variable between different genders. Our study demonstrated no correlation between gender and WETT scores, which is consistent with the result of a meta-analysis assessing the risk factors for olfactory and gustatory dysfunction in patients with COVID-19 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. On the other hand, we demonstrated that the taste score was negatively correlated with participants\u0026rsquo; age in either the patient or the control group, which is relevant to other studies[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Our findings support the idea that taste loss is not just a subjective complaint but a real, measurable symptom in early COVID-19, which can occur independently of smell loss. This is suggestive of a distinct pathophysiological mechanism. This divergence has also been observed in other studies using quantitative tools[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRegarding individual taste qualities, we found that sour, bitter, and umami scores were significantly lower in the COVID-19 group. This is in line with Minichetti et al., who indicated that patients mostly self-reported deficits in sour, bitter, and umami. They also demonstrated in a three-year follow-up, patients with persistent chemosensory dysfunction had lower scores in sweet, sour, bitter, and umami tastes using the Brief Waterless taste test (BWETT) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Asadi reported hypersensitivity to salt in COVID-19 patients, while the sensitivity to sweet, sour, and umami was reduced [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. On the other hand, Cao et al. found no taste differences among recently infected healthcare workers using the Brief Self-Administered Waterless Empirical Taste Test [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], while Sharetts et al. also reported normal taste scores post-COVID. In contrast, Vaira et al. reported hypogeusia in over 60% of patients using the Taste Strips Test, especially for bitter and sour [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. These varying findings may reflect differences in study timing, populations, or methods of taste assessment. Pro-inflammatory cytokines may selectively affect the perception of certain taste qualities. Supporting this, Patel et al. reported lower salivary levels of taste-related proteins like Sonic Hedgehog and Gustin in long-COVID patients, correlating with bitter taste impairment even when total WETT scores were normal [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e Beyond cellular mechanisms, the oral and tongue microbiome may also play a role in the etiology of gustatory dysfunction. COVID-19 has been associated with reduced microbial diversity and an increased abundance of pro-inflammatory bacteria such as Prevotella and Fusobacterium. These changes can disrupt immune balance around the taste buds and trigger local inflammation. Recent studies suggest that shifts in the lingual microbiome can influence taste perception through both immune and metabolic pathways [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The microbiome may act as both a mediator of dysfunction and a possible therapeutic target, and its therapeutic potential can be investigated in future studies.\u003c/p\u003e\u003cp\u003eTaken together, the literature highlights a multifactorial basis for gustatory deficits in COVID-19, involving direct viral damage, immune-mediated suppression of taste cell renewal, altered salivary protein composition, and microbiome dysbiosis [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eOlfactory Dysfunction:\u003c/h2\u003e\u003cp\u003eConsistent with a large body of literature, our study confirmed significant olfactory impairment in the COVID-19 group. Patients exhibited significantly lower median smell scores (6 vs. 7, p\u0026thinsp;=\u0026thinsp;0.002) and a markedly different distribution of function, with substantially higher rates of objectively identified microsmia (56.7% vs. 26.7%) and anosmia (10% vs. 3.3%) compared to controls. Overall, 66.7% of COVID-19 patients had measurable olfactory impairment, and the odds of smell dysfunction were over four times higher in this group (OR\u0026thinsp;=\u0026thinsp;4.67). It aligns with the findings of Hannum et al., who reported a pooled prevalence of 77% for objectively measured olfactory loss, significantly higher than estimates based on patient self-reporting[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This discrepancy between subjective and objective data underscores the importance of using standardized smell tests to capture the true burden of dysfunction, which may otherwise go unrecognized.\u003c/p\u003e\u003cp\u003eNotably, olfactory impairment was associated with age in COVID-19 patients and it was not related to the smoking status of patients. These findings align with a meta-analysis study on risk factors of olfactory dysfunction [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, according to previous reports, female gender and smoking are predictive of persistent olfactory loss among demographic characteristics[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The SARS-CoV-2 variants are another factor affecting the incidence of chemosensory dysfunction, as the Omicron variant is associated with a lower rate of olfactory dysfunction compared to the alpha or delta variants [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur results regarding olfactory impairment are consistent with the long-term findings of both Sharetts et al. and Chiang \u0026amp; Jiang, who also reported significantly lower UPSIT scores and persistent olfactory dysfunction in individuals with a history of COVID-19, even months to a year post-infection [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Similarly, Moein et al. found that one-third of patients continued to experience smell impairment up to 10 weeks post-onset[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This collective evidence suggests that while taste function may recover more readily for many, olfactory dysfunction is often a more persistent sequela of the infection.\u003c/p\u003e\u003cp\u003eWhile we observed a weak positive correlation between olfactory scores and symptom duration, suggesting some potential for recovery within our study timeframe, longer follow-up would be necessary to confirm sustained improvement. Some studies have indicated that chemosensory dysfunction might be associated with low severity of COVID-19[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], although our study was not designed to assess this correlation.\u003c/p\u003e\u003cp\u003eHistopathologic changes, such as squamous metaplasia and replacement of the OE with respiratory-type epithelium, mirror those seen in chronic rhinosinusitis and may compromise the OE\u0026rsquo;s ability to regenerate. At the same time, local immune activation, particularly involving macrophages and dendritic cells, can create a chronic inflammatory microenvironment that suppresses neurogenic signaling pathways, including Wnt, Notch, and NF-κB, further restricting recovery [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Neuroimaging studies have revealed that COVID-19-related anosmia is associated with structural changes and volume loss in limbic and memory-related brain regions such as the hippocampus, amygdala, and orbitofrontal cortex. Such findings are concerning, as they are similar to the patterns seen in neurodegenerative diseases like Alzheimer\u0026rsquo;s and may reflect accelerated brain aging [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. These findings highlight the importance of following patients over time to better understand whether the brain changes seen in those with COVID-19-related smell loss might increase their risk for developing memory problems or neurodegenerative diseases later in life.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eTherapeutic implication:\u003c/h2\u003e\u003cp\u003eAbout 5% of people with chemosensory loss following COVID-19 had sustained olfactory or taste dysfunction six months later [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Given the prevalence and impact of chemosensory dysfunction, various interventions have been proposed. Olfactory training, involving repeated exposure to a set of odors over time, remains the most evidence-based approach for post-viral olfactory loss and may also benefit COVID-19-related anosmia [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. A narrative review indicated that COVID-19 leads to a chronic inflammatory state, and the level of inflammatory cytokines such as IL-4 and IL-6 is still upregulated. Therefore, many immunomodulatory interventions have been applied in this condition, including local corticosteroids and Platelet-Rich Plasma (PRP) [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFor taste disorders, few specific treatments exist. Zinc supplementation has shown modest benefit in select viral etiologies, though evidence in COVID-19 remains limited [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Ongoing research into neuroprotective and anti-inflammatory agents can be considered as therapeutic agents for managing persistent sensory loss.\u003c/p\u003e\u003cp\u003eThis study possesses several limitations. Firstly, the cross-sectional nature of this study limits the ability to assess the progression or recovery of olfactory and gustatory dysfunction over time. Longitudinal studies are needed to evaluate the persistence or resolution of sensory deficits. Secondly, Participants were recruited from a specific geographic and clinical setting in Iran, which may limit the generalizability of findings. Third, the sample size may limit the power to detect smaller but clinically meaningful differences or to perform subgroup analyses. Another limitation is the lack of assessment of inflammatory biomarkers, which could help clarify the biological mechanisms underlying the observed dysfunctions.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this study provides objective evidence for significant impairment of both taste and smell function in patients assessed over the early phase of COVID-19 diagnosis compared to matched controls. The acute phase gustatory dysfunction suggests that taste dysfunction should be recognized as an important and measurable symptom of COVID-19, with implications for both clinical screening and understanding long-term recovery trajectories. The PST olfactory findings align with extensive literature demonstrating frequent smell loss following COVID-19 infection. These results highlight the distinct impacts of SARS-CoV-2 on both chemosensory systems and reinforce the critical importance of employing objective testing methodologies in evaluating these symptoms.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003eRichard L. Doty received consulting fees from Johnson \u0026amp; Johnson and Merck, and royalty payments from Cambridge University Press, Elsevier, Johns Hopkins University Press, McGraw-Hill, and John Wiley \u0026amp; Sons outside the submitted work. He is president and major shareholder of Sensonics International, the manufacturer of the taste test used in this study. The remaining authors declare no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u003c/strong\u003e EK contributed to the study design, data collection, data analysis, and drafting the manuscript. STM was involved in conceptualization and study design, provided administrative support, contributed to data collection and interpretation, participated in drafting and revising the manuscript, and supervised the project. AHD contributed to drafting the manuscript. HRB participated in conceptualization, study design, data interpretation, and manuscript revision. RLD contributed to conceptualization and study design, supervised the project, and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNo funding is received from any funding parties.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical declarations\u003c/strong\u003e: This study was reviewed and approved by the Research Ethics Committee of Iran University of Medical Sciences with the reference number of IR.IUMS.FMD.REC.1400.598. This project was conducted in accordance with the latest version of the Helsinki Declaration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u0026nbsp;\u003c/strong\u003eThe datasets are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u003c/strong\u003e The Authors would like to express their gratitude to their fellow colleagues in Iran University of Medical Sciences, the Institute for Research in Fundamental Sciences, and Sensonics International for their support and contribution.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlves, L.S.M., et al., \u003cem\u003eChanges in taste perception in elderly population and its potential impact on oral health: a systematic review with meta-analysis.\u003c/em\u003e Frontiers in Oral Health, 2024. \u003cstrong\u003e5\u003c/strong\u003e: p. 1517913.\u003c/li\u003e\n\u003cli\u003eManiaci, A., et al., \u003cem\u003eTaste and smell disorders: a critical look at olfactory and gustatory dysfunction\u003c/em\u003e. 2024, MDPI. p. 301.\u003c/li\u003e\n\u003cli\u003eXydakis, M.S., et al., \u003cem\u003eSmell and taste dysfunction in patients with COVID-19.\u003c/em\u003e The Lancet Infectious Diseases, 2020. \u003cstrong\u003e20\u003c/strong\u003e(9): p. 1015-1016.\u003c/li\u003e\n\u003cli\u003eHannum, M.E., et al., \u003cem\u003eTaste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.\u003c/em\u003e Chemical senses, 2023. \u003cstrong\u003e48\u003c/strong\u003e: p. bjad043.\u003c/li\u003e\n\u003cli\u003eMoein, S.T., et al. \u003cem\u003ePrevalence and reversibility of smell dysfunction measured psychophysically in a cohort of COVID‐19 patients\u003c/em\u003e. in \u003cem\u003eInternational forum of allergy \u0026amp; rhinology\u003c/em\u003e. 2020. 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A prospective study using psychophysical testing\u003c/em\u003e. in \u003cem\u003eInternational Forum of Allergy \u0026amp; Rhinology\u003c/em\u003e. 2021.\u003c/li\u003e\n\u003cli\u003eSoter, A., et al., \u003cem\u003eAccuracy of self‐report in detecting taste dysfunction.\u003c/em\u003e The Laryngoscope, 2008. \u003cstrong\u003e118\u003c/strong\u003e(4): p. 611-617.\u003c/li\u003e\n\u003cli\u003eVon Elm, E., et al., \u003cem\u003eThe Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.\u003c/em\u003e The lancet, 2007. \u003cstrong\u003e370\u003c/strong\u003e(9596): p. 1453-1457.\u003c/li\u003e\n\u003cli\u003eDoty, R.L., C. Wylie, and M. 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Jiang, \u003cem\u003eEffect of oral zinc and steroids on long COVID hyposmia and hypogeusia.\u003c/em\u003e SAGE Open Medicine, 2024. \u003cstrong\u003e12\u003c/strong\u003e: p. 20503121241301894.\u003c/li\u003e\n\u003cli\u003eDoty, R.L., R. Sharetts, and S.T. Moein. \u003cem\u003eSelf‐Administered Taste Testing Without Water: Normative Data for the 53‐Item Waterless Empirical Taste Test (WETT)\u003c/em\u003e. in \u003cem\u003eInternational Forum of Allergy \u0026amp; Rhinology\u003c/em\u003e. 2025. Wiley Online Library.\u003c/li\u003e\n\u003cli\u003eVaira, L.A., et al., \u003cem\u003eObjective evaluation of anosmia and ageusia in COVID‐19 patients: single‐center experience on 72 cases.\u003c/em\u003e Head \u0026amp; neck, 2020. \u003cstrong\u003e42\u003c/strong\u003e(6): p. 1252-1258.\u003c/li\u003e\n\u003cli\u003eMinichetti, D.G., et al., \u003cem\u003eDeterminants of persistence and recovery of chronic coronavirus disease 2019 chemosensory dysfunction.\u003c/em\u003e Journal of Allergy and Clinical Immunology, 2025. \u003cstrong\u003e155\u003c/strong\u003e(1): p. 120-134.\u003c/li\u003e\n\u003cli\u003eAsadi, M.M., et al., \u003cem\u003eQuantitative analysis of taste disorder in COVID-19 patients, the hypersensitivity to salty quality.\u003c/em\u003e New microbes and new infections, 2021. \u003cstrong\u003e43\u003c/strong\u003e: p. 100919.\u003c/li\u003e\n\u003cli\u003eCao, A.C., et al., \u003cem\u003eObjective screening for olfactory and gustatory dysfunction during the COVID-19 pandemic: a prospective study in healthcare workers using self-administered testing.\u003c/em\u003e World Journal of Otorhinolaryngology-Head and Neck Surgery, 2022. \u003cstrong\u003e8\u003c/strong\u003e(03): p. 249-256.\u003c/li\u003e\n\u003cli\u003eSrinivasan, M., \u003cem\u003eTaste dysfunction and long COVID-19.\u003c/em\u003e Frontiers in cellular and infection microbiology, 2021. \u003cstrong\u003e11\u003c/strong\u003e: p. 716563.\u003c/li\u003e\n\u003cli\u003evon Bartheld, C.S. and L. Wang, \u003cem\u003ePrevalence of olfactory dysfunction with the omicron variant of SARS-CoV-2: a systematic review and meta-analysis.\u003c/em\u003e Cells, 2023. \u003cstrong\u003e12\u003c/strong\u003e(3): p. 430.\u003c/li\u003e\n\u003cli\u003eMeunier, N., et al., \u003cem\u003eCOVID 19-induced smell and taste impairments: putative impact on physiology.\u003c/em\u003e Frontiers in physiology, 2021. \u003cstrong\u003e11\u003c/strong\u003e: p. 625110.\u003c/li\u003e\n\u003cli\u003eXie, Y., et al., \u003cem\u003eAging and chronic inflammation: impacts on olfactory dysfunction-a comprehensive review.\u003c/em\u003e Cellular and Molecular Life Sciences, 2025. \u003cstrong\u003e82\u003c/strong\u003e(1): p. 199.\u003c/li\u003e\n\u003cli\u003eLeon, M., E.T. Troscianko, and C.C. Woo, \u003cem\u003eInflammation and olfactory loss are associated with at least 139 medical conditions.\u003c/em\u003e Frontiers in Molecular Neuroscience, 2024. \u003cstrong\u003e17\u003c/strong\u003e: p. 1455418.\u003c/li\u003e\n\u003cli\u003eOjha, P. and A. Dixit, \u003cem\u003eOlfactory training for olfactory dysfunction in COVID‐19: A promising mitigation amidst looming neurocognitive sequelae of the pandemic.\u003c/em\u003e Clinical and Experimental Pharmacology and Physiology, 2022. \u003cstrong\u003e49\u003c/strong\u003e(4): p. 462-473.\u003c/li\u003e\n\u003cli\u003eYan, C.H., et al. \u003cem\u003eUse of platelet‐rich plasma for COVID‐19\u0026ndash;related olfactory loss: a randomized controlled trial\u003c/em\u003e. in \u003cem\u003eInternational Forum of Allergy \u0026amp; Rhinology\u003c/em\u003e. 2023. Wiley Online Library.\u003c/li\u003e\n\u003cli\u003eSteffens, Y., et al., \u003cem\u003eEffectiveness and safety of PRP on persistent olfactory dysfunction related to COVID-19.\u003c/em\u003e European Archives of Oto-Rhino-Laryngology, 2022. \u003cstrong\u003e279\u003c/strong\u003e(12): p. 5951-5953.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Olfaction function, Smell dysfunction, Gustatory function, Taste dysfunction, COVID-19","lastPublishedDoi":"10.21203/rs.3.rs-7917937/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7917937/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e Taste and smell dysfunction are hallmark symptoms ofCoronavirus Disease (COVID-19). While objective assessment of chemosensory function is critical for accurate evaluation, most prior studies have relied on self-report measures, and data from non-Western populations remain limited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To objectively assess gustatory and olfactory function in recently diagnosed COVID-19 patients compared to age- and sex-matched healthy controls using validated tools in an Iranian population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In this prospective cross-sectional study, 30 COVID-19 patients and 30 matched healthy controls were enrolled between February and March 2022 in Tehran, Iran. Gustatory function was assessed using the Waterless Empirical Taste Test (WETT), and olfactory function was evaluated using the Pocket Smell Test (PST).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eCOVID-19 patients demonstrated significantly lower mean WETT scores compared to controls [16.14 (SD= 4.06) vs. 18.73 (SD=5.06), \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05], with sour, bitter, and umami tastes significantly affected. Smell scores were also significantly lower among patients [6 (Interquartile Range (IQR)=5–7) vs. 7 (IQR=6–8), \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05]. Among COVID-19 patients, 10% were anosmic and 56.7% microsmic. The odds of smell dysfunction were significantly higher in the COVID-19 group (OR = 4.67, 95% CI: 1.57–13.87).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eCOVID-19 is associated with measurable impairments in both gustatory and olfactory function, particularly in sour, bitter, and umami modalities. There wasn’t any correlation between olfactory and gustatory test scores.\u003c/p\u003e","manuscriptTitle":"A Comparative Evaluation of Taste and Smell Dysfunction in COVID-19: A Cross-sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-11 16:27:51","doi":"10.21203/rs.3.rs-7917937/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6fca2c21-57e5-4b8f-81cb-10de7367e42e","owner":[],"postedDate":"November 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":57677069,"name":"Health sciences/Diseases"},{"id":57677070,"name":"Health sciences/Health care"},{"id":57677071,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-11-17T13:23:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-11 16:27:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7917937","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7917937","identity":"rs-7917937","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}