Psychological Impact and Clinical Correlates of Olfactory Dysfunction in Post- COVID-19 and Non-COVID-19 Patients: A Comparative Study

doi:10.21203/rs.3.rs-4617956/v1

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Psychological Impact and Clinical Correlates of Olfactory Dysfunction in Post- COVID-19 and Non-COVID-19 Patients: A Comparative Study

https://doi.org/10.21203/rs.3.rs-4617956/v1

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Olfactory dysfunction (OD) has been reported in individuals who have recovered from COVID-19. Those with OD after COVID-19 (COVID-19 group) exhibited more severe psychiatric symptoms than those with OD from other etiologies (non-COVID-19 group). This study aimed to investigate the differences in psychological symptoms and related clinical factors between the two groups.

Fifty-two participants (26 COVID-19 group; 26 non-COVID-19 group) were recruited. Both objective and subjective olfactory function were assessed. Symptoms of depression, anxiety, and perceived stress were measured using self-report scales.

There were no significant differences in objective and subjective olfactory function or psychological symptoms between the groups, except for age and the short version of the Questionnaire of Olfactory Disorders-negative statements (sQOD-NS). The sQOD-NS score was negatively correlated with the duration of OD only in the COVID-19 group. Both groups showed significant correlations between the sQOD-NS and the Patient Health Questionnaire-9 (PHQ-9) scores. Mediation analysis showed that the duration of OD indirectly affected PHQ-9 scores via sQOD-NS in the entire sample and particularly in the COVID-19 group.

The findings suggest that subjective distress from OD may mediate the relationship between duration of OD and depressive symptoms in COVID-19 patients, highlighting the need for targeted psychiatric interventions after COVID-19.

Biological sciences/Neuroscience

Health sciences/Medical research

Health sciences/Signs and symptoms

Olfaction Disorders

COVID-19

Depressive Disorder

Anxiety Disorders

Psychological distress

Olfactory dysfunction (OD) refers to a range of conditions involving impaired sense of smell, including anosmia (complete loss of smell) and hyposmia (reduced ability to smell).¹ OD can occur due to a variety of causes, including rhinosinusitis with or without nasal polyps, post viral infections, head trauma, toxic material exposure, and congenital disorders.^2,3 In recent years, the prevalent of OD has been increased due to the COVID-19 pandemic, with many patients experiencing a decrease in their sense of smell following infection.^4,5 The prevalence of OD following COVID-19 pandemic has been reported to range from approximately 10–55%, depending on race.⁶ COVID-19 related OD often appears on the third day following infection and goes away entirely in 4–6 weeks. But these changes can last longer than four months in 27% of cases⁷ and up to a year in 21.3% of cases.⁸

According to Yom-Tov et al., COVID-19 patients with OD had a 30% higher incidence of depression and suicidal ideation than those without OD.⁹ A online survey conducted by Coelho et al. on 322 OD subjects following COVID-19 infection also found that symptoms depression were present in 43% of participants.¹⁰ Additionally, COVID-19 patients with OD reported higher anxiety levels.¹¹ These results suggested a correlation between neuropsychiatric symptoms and OD, and the pivotal role of COVID-19 infection in long term mental health outcome.

Previous studies have proposed several hypothesized mechanisms for the development of neuropsychiatric symptoms in COVID-19 related OD. It has been demonstrated that SARS-CoV-2 can cause damage to the central nervous system.^12,13 Postmortem examination of brain tissues from patients with COVID-19 revealed the presence of neuroinflammation, microglia activation, and neuronal death.^14,15 Neuroinflammation can persist long after the acute phase of the disease, sometimes referred to as long COVID.¹⁶ According to Stefanou et al., over one-third of patients experienced brain fog, cognitive dysfunction, changes in gustation and smell, and psychiatric manifestations like mood disorders as long COVID symptoms.¹³ This phenomenon is thought to be likely caused by persistent systemic inflammation and the existence of viral RNA in the brains of COVID-19 patients after an extended length of time.¹⁷

In the psychosocial perspectives, OD can cause problems in various emotional aspects of human life. The inability to smell can lead to a loss of pleasure from activities that were once enjoyed, such as eating and socializing, and this can cause significant psychological distress to the affected person.^18,19 Several lines of evidence demonstrate a significant association between OD and depression, anxiety, and feelings of isolation, which can further exacerbate one's quality of life (QoL).^19–21 In a study long COVID, distortion of smell was more prevalent in young people, and negative QoL were more common in people with a post-COVID-19 infection than in other post-infection cases.²² Therefore, OD following COVID-19 also can elicit profound negative impact on psychological well-being and require clinical attention.

However, it is not yet clear why the prevalence of psychological symptoms is higher in patients with COVID-19-related OD compared to OD due to other etiologies, such as chronic entorhinal inflammation or trauma. To date, no studies have been conducted to compare the stress level, symptoms of depression and anxiety followed by OD related with COVID-19 infection and that resulted from other etiologies. Furthermore, clinical factors that influence mood symptoms in the long COVID population remain poorly understood.

In this study, we aimed to compare the olfactory function and emotional state of two groups: those who experienced OD due to COVID-19 infection and those who experienced long-term olfactory loss due to chronic entorhinal disease. Additionally, we investigated the potential associations among the duration of OD, subjective distress, and mood symptoms such as depression and anxiety using mediation analyses.

The demographics of the patients are presented in Table 1. The mean age of the participants was approximately 44 years old, with the COVID-19 group being significantly younger than the non-COVID-19 group. Among the 52 participants with subjective olfactory loss approximately 71% were confirmed to have OD according to psychophysical test results. The subjective and objective olfactory parameters did not differ significantly between the COVID-19 and non-COVID-19 groups except QOD-NS total score (11.08 ± 5.05 vs 7.81 ± 5.47, p = .030). Based on the cut-off of each psychological measure, 38.5% of the participants were considered to have depressive symptoms (20/52), and 21.2% of participants were considered to have moderate to severe anxiety (11/52). Furthermore, 78.8% of participants were considered to have moderate to severe perceived stress (41/52).

Table 1

Demographics of the participants. QOD, Questionnaire of Olfactory Disorders; VAS, visual analog scale; sQOD-NS, short version of QOD-negative statements; YOF, YSK olfactory function; PHQ-9, Patient Health Questionnaire-9; GAD-7, Generalized Anxiety Disorder 7-item scale; PSS-10, Perceived Stress Scale
	Total (n = 52)	COVID-19 (n = 26)	Non-COVID-19 (n = 26)	P value
Age (year-old)	44.21 ± 18.24	39.23 ± 16.12	49.19 ± 19.16	.048
Sex (male)	27	14	13	.781
sQOD-NS total score	9.44 ± 5.47	11.08 ± 5.05	7.81 ± 5.47	.030
QOD-VAS total score	32.31 ± 11.33	31.85 ± 9.64	32.77 ± 12.97	.772
YOF total score	15.91 ± 7.47	16.99 ± 7.00	14.84 ± 7.90	.303
Patients with objective OD (n)	37	19	18	.760
PHQ-9 score	8.23 ± 6.77	7.27 ± 6.10	9.19 ± 7.37	.310
GAD-7 score	5.24 ± 5.61	3.79 ± 5.13	6.64 ± 5.80	.076
PSS-10	18.04 ± 6.48	17.58 ± 7.53	18.46 ± 5.44	.637

Among 38 subjects, duration of OD did not differ significantly between the COVID-19 and the non-COVID-19 group (3.83 ± 3.22 vs. 3.34 ± 2.97, p = .625). According to correlation analysis about various olfactory function and psychologic parameters, the sQOD-NS was negatively correlated with duration of OD with marginal significance (Table 2). The correlation analysis between duration of OD and PHQ-9, GAD-7 or PSS-10 did not reach significance. In contrast, sQOD-NS demonstrated a significant correlation with PHQ-9 and GAD-7. The QOD-VAS also exhibited a moderate to high correlation with PHQ-9 and GAD-7, and low correlation with PSS-10. However, the total YOF score showed negligible or no correlation with the psychologic parameters. In the COVID-19 group, a significant negative correlation was observed between the duration of OD and sQOD-NS (Fig. 1A). In contrast, no such correlation was found in the non-COVID-19 group. The sQOD-NS and PHQ-9 exhibited a significant correlation in both groups (Fig. 1B), whereas the correlation between sQOD-NS and GAD-7 did not reached the level of significance (Fig. 1C).

Table 2

Spearman’s correlation matrix of olfactory function and psychological variables (n = 38)
	Variables	1	2	3	4	5	6	7	8
1	Age	1
2	Duration of OD	.011	1
3	sQOD-NS	− .107	− .318^†	1
4	QOD-VAS	.064	.123	− .567^**	1
5	YOF, total	− .205	− .242	− .149	.242	1
6	PHQ-9	.032	− .107	− .539^**	.715^**	.179	1
7	GAD-7	.035	− .242	− .471^**	.644^**	.136	.838^**	1
8	PSS-10	.093	− .131	− .160	.461^**	.260	.372^*	.488^**	1
† p = .051; * p < .05; **p < .01 OD, olfactory dysfunction; QOD, Questionnaire of Olfactory Disorders; VAS, visual analog scale; sQOD-NS, short version of QOD-negative statements; YOF, YSK olfactory function; PHQ-9, Patient Health Questionnaire-9; GAD-7, Generalized Anxiety Disorder 7-item scale; PSS-10, Perceived Stress Scale

A mediation model with sQOD-NS as the mediator showed a significant indirect effect (Fig. 2A; effect size, 0.47; 95% Bootstrap CI [0.10, 1.04]) of duration of OD on PHQ-9 in the whole subject. In the COVID-19 group (n = 20), mediation effects were observed between duration of OD and PHQ-9 score through the sQOD-NS (Fig. 2B; effect size, 0.30; 95% Bootstrap CI [0.00, 0.92]). However, there was no significant indirect effect of duration of OD on PHQ-9 mediated by the sQOD-NS (Fig. 2C; effect size, 0.68; 95% Bootstrap CI [-0.24, 1.68]) in the non-COVID-19 group.

In the whole subject, an indirect effect of sQOD-NS was also significant in the mediation model using GAD-7 as a dependent variable (Fig. 3; effect size, 0.38; 95% Bootstrap CI [0.09, 0.88]). However, no significance of sQOD-NS as a mediator was found in the subgroup analyses the COVID-19 (effect size, 0.23; 95% Bootstrap CI [-0.14, 0.83]) and non-COVID-19 groups (effect size, 0.47; 95% Bootstrap CI [-0.15, 1.24]).

The purpose of the current study was to determine any differences in psychological symptoms between people with post-COVID-19-related OD and non-COVID-19 cases. The comparison of both groups did not demonstrate significant differences in clinical characteristics and symptoms of depression, anxiety and perceived stress, except age and sQOD-NS score. In the COVID-19 group, the sQOD-NS score was found to have a significant negative correlation with the duration of OD whereas the non-COVID-19 group was not. Additionally, significant correlation results between sQOD-NS and PHQ-9 were found in both groups. The mediation analysis demonstrated a significant indirect effect of the duration of OD on PHQ-9 scores via the sQOD-NS scores in the whole subjects and in the COVID-19 group, respectively.

The existing literature has identified significant associations between OD and mood symptoms.^9–11,23 The causes of OD were diverse, encompassing a range of conditions, including those related to the SARS-CoV-2 infection, entorhinal diseases, and trauma. However, it is not yet known whether the mechanism of psychological symptoms differs between people who have experienced an OD following COVID-19 and those who have not. To the best of our knowledge, this is the first study to demonstrate that the relevant clinical factors associated with psychological symptoms after the onset of OD may be varied by its etiology.

In this study, approximately 70% of patients who reported subjective OD were diagnosed with actual olfactory impairment through psychophysical tests. These inconsistencies between subjective and objective olfactory test results have been reported in a previous study.²⁴ Compared to the non-COVID-19 group, the COVID-19 group had younger age, and reported less subjective distress (sQOD-NS). In addition, there was no significant difference between groups, in terms of depression, anxiety and stress as well as duration of OD. The present findings differ from those of Stankevice and colleagues,²² who found that people infected with SARS-CoV-2 had a greater complaint rate for distorted sensation but had a lower prevalence of olfactory abnormalities. The sample size and participant characteristics may have an impact on these findings.

On the other hand, the correlation results for sQOD-NS scores demonstrated disparate patterns between groups. In the COVID-19 group, sQOD-NS scores had significant correlation with PHQ-9 scores as well as duration of OD, while non-COVID-19 group did not. These findings demonstrated that despite having less subjective distress, the COVID-19 group displayed a clear pattern of correlation in response to the length of OD and a moderate impact on the severity of depression. However, we could not find signficant correlation between duration of OD and depressive symptoms. Current results are in line with earlier research showing that the depressive symptom was significantly correlated with solely COVID-19 related OD.²⁵ Furthermore, Liu et al. also reported that QOD-NS score was a strong predictor of the depressive symptom in OD patients, while duration of OD was not.²⁵ This is also consistent with our findings.

In the mediation analyses, there was an significant indirect mediation effect of between duration of OD and PHQ-9 in the entire subject, and also in the COVID-19 group. In contrast, the direct effect of duration of OD on PHQ-9 was not sigificant, had opposite effects to indirect pathway. This pattern of coefficients might indicate a suppressor effect of sQOD-NS. This particular mediational path suggest that, the participants with high sQOD-NS would not have long-term reduction of depressive symptoms. Patients with COVID-19 may have expected that once they had recovered from the symptoms of infection, they would also recover from the resulting loss of smell. However, in some patients, recovery can be markedly delayed, with OD persisting for months or longer after its onset.²⁶ This discrepancy may influence subjective distress and result in the emergence of additional psychological symptoms. In contrast, this mediating effect was not evident for the non-COVID-19 group, because OD may be a chronic and predictable course of underlying disease in this group.

In this study, approximately 70% of patients who reported subjective olfactory impairment were diagnosed with actual olfactory impairment through psychophysical tests. However, the results of this study indicated that subjective olfactory impairment, rather than objective finding is significantly correlated with depressive symptoms among COVID-19 patients. This finding aligns with earlier studies suggesting that the subjectivity of sensory perception might be a crucial factor, potentially even surpassing the significance of the perceptual problem in the groups with post-COVID-19 OD.²⁷ This highlighted the importance of assessment of mental health problems in individuals with subjective OD after COVID-19 infection.

This study has several limitations. First, the study employed self-report scales to assess depression, anxiety, and stress in the participants. However, expert interviews for checking current and past mental illness were not conducted. This raises the possibility that some participants may have had pre-existing mental health issues prior to the onset of OD. Second, this study only focused on patients who visited the hospital with subjective symptoms of OD and did not include an analysis of the population without OD. This may result in a sampling bias. Finally, the mediation analysis was based on patients who clearly recalled the duration of the OD. Some participants were unable to recall the exact time point of their OD, then excluded from the analysis. Therefore, it is recommended that future studies should include a larger number of participants and collect comprehensive data, including the duration of OD and various factors that may influence the mental health outcome.

In conclusion, we could find a substantial indirect influence of OD duration on PHQ-9 scores via sQOD-NS scores in the COVID-19 group, even though there were no discernible differences between the levels of anxiety, depression, or perceived stress compared with non-COVID-19 group. The results of this study indicate that high subjective distress from OD, even after recovery from COVID-19 symptoms, might have a negative impact on mental health outcomes. Accordingly, it is imperative that we need to endeavor to proactively identify and address subjective distress from patients with OD after COVID-19, adopting an assertive approach to treatment, with the objective of fostering long-term mental health outcomes.

Study population

This retrospective cohort study included 52 patients who presented with subjective olfactory dysfunction and visited our tertiary hospital between January 2022 and August 2023. Patients who had already been diagnosed with psychiatric diseases or had other underlying neurological diseases were excluded from this study. Diagnosis of COVID-19 was confirmed by SARS-CoV-2 real-time reverse transcription polymerase chain reaction (RT-PCR) using respiratory samples. And the COVID-19 associated olfactory dysfunction was determined based on the patient's statements. If the patient reported that previously not having any smell-related issues and the onset of olfactory dysfunction after and linked it to their COVID-19 diagnosis, it was regarded as COVID-19-associated olfactory dysfunction (COVID-19 group). In patients with OD which not associated with COVID-19 (non-COVID-19 group), the causes of OD included head trauma (n = 5), brain hemorrhage (n = 1), post-SARS-CoV-2 mRNA vaccination (n = 2), post-upper respiratory infection (n = 2), chronic rhinosinusitis (n = 2), iatrogenic causes (n = 1, anterior skull base surgery for olfactory groove meningioma), and unknown etiologies (n = 13). All participants completed subjective and objective evaluations of their olfaction, and a psychological assessment was conducted using various questionnaires. The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of our tertiary Hospital (2023AS0087). Written Informed consent was acquired from all study participants.

Evaluation of olfaction

We evaluated subjective olfactory function using the Korean version of the Questionnaire of Olfactory Disorders (QOD).²⁸ Among the subdomains of the QOD questionnaire, we used the QOD-visual analog scale (QOD-VAS) and the short version of QOD-negative statements (sQOD-NS). The Korean version of QOD-VAS comprises five questions with an 11-point scale (0–10), and a higher score indicates poor subjective olfactory function. On the other hand, the Korean version of sQOD-NS consists of seven questions with a 4-point scale (0–3), and a higher score indicates better subjective olfactory function. Objective olfactory function was evaluated using psychophysiological YSK olfactory function (YOF) test.²⁹ The YOF test consists of three subtests for threshold (T), discrimination (D), and identification (I) using Korean familiar odorants. The YOF subtests had a core range of 1–12 for the threshold test, 0–12 for the discrimination and identification tests, and 1–36 for the total TDI score. The diagnostic cutoff for the YOF test was established as ≤ 14.5 for anosmia and ≤ 21.0 for hyposmia.²⁹

Evaluation of psychological distress.

Various psychological assessments were performed using Korean version of the Patient Health Questionnaire-9 (PHQ-9) for evaluation of depressive mood, Generalized Anxiety Disorder 7-item scale (GAD-7) for evaluation of anxiety and Perceived Stress Scale (PSS-10) for stress level assessment.

The PHQ-9 is a self-report questionnaire that was designed for use in primary care settings to efficiently establish psychiatric diagnoses based on DSM-IV criteria.³⁰ It is composed of 9 items, and respondents are asked to select the degree of their symptoms on a scale of 0 to 3 for each item. The scores are then added up to give a total score out of 27, with a cut-off point of 10 used to indicate the presence of depressive symptoms.

The GAD-7 is a self-rated assessment that was developed by Spitzer et al. to screen for generalized anxiety disorder in primary care populations.³¹ The GAD-7 is composed of 7 items, and respondents are asked to select the degree of their symptoms on a scale of 0 to 3 for each item with a cut-off point of 9 used to screening for anxiety.³¹

The PSS-10 is a self-rated assessment developed by Cohen et al. to assess an individual's overall perception and interpretation of stress experienced during the past month, rather than specific stressful events.³² The PSS-10 is composed of 10 items, and respondents are asked to select the degree of their symptoms using 5-point Likert scale (0–4). The PSS-10 is not intended for diagnostic purposes, and thus, there is no universally accepted cut-off score for interpreting PSS-10 scores for each item. However, Swaminathan et al. have previously proposed criteria for classifying the degree of perceived stress in patients according to the following standards: low perceived stress (0–13), moderate perceived stress (14–26), and high perceived stress (27–40). Therefore, the present researchers classified the level of stress in patients according to these criteria.

Statistics

Statistical analysis was conducted using the Statistical Package for the Social Sciences version 21 (IBM Corporation, Armonk, NY, USA). The χ² test was used to compare categorical variables, and the independent T test was used to compare continuous variables between patient groups based on their experience of olfactory impairment. Furthermore, Spearman’s correlation coefficient was used to assess the relationship between olfactory assessment and psychological parameters. The magnitude of the correlation coefficient (Spearman’s rho) was interpreted using Hinkle’s suggestion (very high: 0.9 to 1.00; high: 0.7 to 0.9; moderate: 0.5 to 0.7; low: 0.3 to 0.5; negligible correlation: 0 to 0.3).

In addition, we examined the relationship between duration of OD, sQOD-NS and mood symptoms (depression, and anxiety), which showed significant correlation findings with each other. Individuals who were unable to recall the duration of OD were excluded from further analysis, resulting in a total of 38 participants (20 in the COVID-19 group and 18 in the non-COVID-19 group) being included in the mediation analysis.

We postulated that longer duration of OD may increase the severity of mood symptoms (direct effect), and sQOD-NS may serve as a mediating factor between duration of OD and mood symptoms (indirect effect). We performed mediation analyses using the SPSS PROCESS macro³³ with model 4 (single mediator model). The validity of mediation model was examined in three groups: the whole participant, the COVID-19 group, and the non-COVID-19 group. Using bootstrapping, 95% bias-corrected bootstrap confidence intervals [CI] for the indirect effects based on 5,000 bootstrap resamples were calculated.

Competing interests

The authors have no potential conflicts of interest to disclose.

Author Contribution

J.H.Y. and M.Y.S. analyzed the data and wrote the paper. T-S.K. and S.H.L. designed the study and wrote the paper. J.H.Y. and M.Y.S. collected the data. J.S.K., T-S.K. and M.Y.S. reviewed and revised the paper.

Acknowledgement

This study was supported by Korean University Ansan Hospital Grant (O2310621). This research was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C0619).

Data Availability

The datasets generated and/or analyzed during the current study are not publicly available due to information that could compromise the privacy of research participants but are available from the corresponding author on reasonable request.

Hummel, T. et al. Olfactory Dysfunction: Etiology, Diagnosis, and Treatment. Dtsch Arztebl Int 120, 146–154, doi:10.3238/arztebl.m2022.0411 (2023).
Nordin, S. & Bramerson, A. Complaints of olfactory disorders: epidemiology, assessment and clinical implications. Curr Opin Allergy Clin Immunol 8, 10–15, doi:10.1097/ACI.0b013e3282f3f473 (2008).
Mori, J. et al. Clinical study of olfactory disturbance. Acta Otolaryngol Suppl 538, 197–201 (1998).
Seo, M. Y. et al. Trend of Olfactory and Gustatory Dysfunction in COVID-19 Patients in a Quarantine Facility. J Korean Med Sci 35, e375, doi:10.3346/jkms.2020.35.e375 (2020).
Cardoso, C. C. et al. Olfactory Dysfunction in Patients With Mild COVID-19 During Gamma, Delta, and Omicron Waves in Rio de Janeiro, Brazil. JAMA 328, 582–583, doi:10.1001/jama.2022.11006 (2022).
Saniasiaya, J., Islam, M. A. & Abdullah, B. Prevalence of Olfactory Dysfunction in Coronavirus Disease 2019 (COVID-19): A Meta-analysis of 27,492 Patients. Laryngoscope 131, 865–878, doi:10.1002/lary.29286 (2021).
Pasquini, J., Maremmani, C., Salvadori, S., Silani, V. & Ticozzi, N. Testing olfactory dysfunction in acute and recovered COVID-19 patients: a single center study in Italy. Neurol Sci 42, 2183–2189, doi:10.1007/s10072-021-05200-7 (2021).
Frosolini, A. et al. Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series. Brain Sci 12, doi:10.3390/brainsci12040430 (2022).
Yom-Tov, E., Lekkas, D. & Jacobson, N. C. Association of COVID19-induced anosmia and ageusia with depression and suicidal ideation. J Affect Disord Rep 5, 100156, doi:10.1016/j.jadr.2021.100156 (2021).
Coelho, D. H. et al. Quality of life and safety impact of COVID-19 associated smell and taste disturbances. Am J Otolaryngol 42, 103001, doi:10.1016/j.amjoto.2021.103001 (2021).
Dudine, L. et al. Investigation on the Loss of Taste and Smell and Consequent Psychological Effects: A Cross-Sectional Study on Healthcare Workers Who Contracted the COVID-19 Infection. Front Public Health 9, 666442, doi:10.3389/fpubh.2021.666442 (2021).
Beckman, D. et al. SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19. Cell Rep 41, 111573, doi:10.1016/j.celrep.2022.111573 (2022).
Stefanou, M. I. et al. Neurological manifestations of long-COVID syndrome: a narrative review. Ther Adv Chronic Dis 13, 20406223221076890, doi:10.1177/20406223221076890 (2022).
Boroujeni, M. E. et al. Inflammatory Response Leads to Neuronal Death in Human Post-Mortem Cerebral Cortex in Patients with COVID-19. ACS Chem Neurosci 12, 2143–2150, doi:10.1021/acschemneuro.1c00111 (2021).
Colombo, D. et al. Neuropathology and Inflammatory Cell Characterization in 10 Autoptic COVID-19 Brains. Cells 10, doi:10.3390/cells10092262 (2021).
Tai, A. P., Leung, M. K., Lau, B. W., Ngai, S. P. & Lau, W. K. Olfactory dysfunction: A plausible source of COVID-19-induced neuropsychiatric symptoms. Front Neurosci 17, 1156914, doi:10.3389/fnins.2023.1156914 (2023).
Stein, S. R. et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature 612, 758–763, doi:10.1038/s41586-022-05542-y (2022).
Winter, A. L., Henecke, S., Lundstrom, J. N. & Thunell, E. Impairment of quality of life due to COVID-19-induced long-term olfactory dysfunction. Front Psychol 14, 1165911, doi:10.3389/fpsyg.2023.1165911 (2023).
Hummel, T. & Nordin, S. Olfactory disorders and their consequences for quality of life. Acta Otolaryngol 125, 116–121, doi:10.1080/00016480410022787 (2005).
Miwa, T. et al. Impact of olfactory impairment on quality of life and disability. Arch Otolaryngol Head Neck Surg 127, 497–503, doi:10.1001/archotol.127.5.497 (2001).
Schafer, L., Schriever, V. A. & Croy, I. Human olfactory dysfunction: causes and consequences. Cell Tissue Res 383, 569–579, doi:10.1007/s00441-020-03381-9 (2021).
Stankevice, D., Fjaeldstad, A. W., Agergaard, J. & Ovesen, T. Long-Term COVID-19 Smell and Taste Disorders Differ Significantly from Other Post-Infectious Cases. Laryngoscope 133, 169–174, doi:10.1002/lary.30453 (2023).
Bochicchio, V., Mezzalira, S., Maldonato, N. M., Cantone, E. & Scandurra, C. Olfactory-related quality of life impacts psychological distress in people with COVID-19: The affective implications of olfactory dysfunctions. J Affect Disord 323, 741–747, doi:10.1016/j.jad.2022.12.049 (2023).
Seo, M. Y., Choi, W. S. & Lee, S. H. Clinical Features of Olfactory Dysfunction in COVID-19 Patients. J Korean Med Sci 36, e161, doi:10.3346/jkms.2021.36.e161 (2021).
Liu, D. T. et al. Depression Symptoms and Olfactory-related Quality of Life. Laryngoscope 132, 1829–1834, doi:10.1002/lary.30122 (2022).
Favero, R. et al. Olfactory Dysfunction in COVID-19 Patients Who Do Not Report Olfactory Symptoms: A Pilot Study with Some Suggestions for Dentists. Int J Environ Res Public Health 19, doi:10.3390/ijerph19031036 (2022).
Dumas, L. E. et al. Impact of post-COVID-19 olfactory disorders on quality of life, hedonic experiences and psychiatric dimensions in general population. BMC Psychiatry 24, 111, doi:10.1186/s12888-024-05538-0 (2024).
Choi, W. R., Jeong, H. Y. & Kim, J. H. Reliability and validity of the Korean version of the Questionnaire of Olfactory Disorders. Int Forum Allergy Rhinol 8, 1481–1485, doi:10.1002/alr.22186 (2018).
Ha, J. G. et al. Development of a Korean Culture-Friendly Olfactory Function Test and Optimization of a Diagnostic Cutoff Value. Clin Exp Otorhinolaryngol 13, 274–284, doi:10.21053/ceo.2020.00864 (2020).
Spitzer, R. L., Kroenke, K. & Williams, J. B. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA 282, 1737–1744, doi:10.1001/jama.282.18.1737 (1999).
Spitzer, R. L., Kroenke, K., Williams, J. B. & Lowe, B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 166, 1092–1097, doi:10.1001/archinte.166.10.1092 (2006).
Cohen, S. Perceived stress in a probability sample of the United States. (1988).
Hayes, A. F. PROCESS: A versatile computational tool for observed variable mediation, moderation, and conditional process modeling. Retrieved from http://www.afhayes.com/public/process2012.pdf PROCESS. https://doi.org/978-1-60918-230-4 (2012).

No competing interests reported.

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Psychological Impact and Clinical Correlates of Olfactory Dysfunction in Post- COVID-19 and Non-COVID-19 Patients: A Comparative Study

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