Factors associated with loss and recovery of smell and taste after COVID-19 infection

1 INTRODUCTION

The coronavirus disease (COVID-19), caused by the novel coronavirus SARS-CoV-2, is known to negatively impact the respiratory, olfactory, and gustatory organ systems.^{1, 2} Based on recently published systematic reviews and meta-analyses, the prevalence of olfactory dysfunction and gustatory dysfunction is estimated to be between 41−52.7% and 38.2–43.9% among patients who test positive for COVID-19, respectively.^3-6 When combined, the prevalence of loss of smell and taste has an estimated prevalence of 35.1%.³

Individuals who experience loss of taste or smell due to COVID-19 face significant quality of life (QOL) declines, personal safety risks, and job performance challenges. Olfactory dysfunction particularly can lead to less hygiene awareness, loss of appetite, and inability to detect hazards, such as gas, fire, or smoke.^{7, 8} Those with gustatory dysfunction have reported decreased enjoyment in eating, loss of appetite, and difficulty identifying spoiled foods.^{7, 8} Additionally, many individuals have reported depression and reduced enjoyment of life associated with loss of smell and taste, and certain occupational groups have experienced limitations in job performance, leading to job insecurity, financial instability, and eventual search for alternative employment.^7-10

Recovery times from olfactory and gustatory dysfunction can vary among individuals. While most recover some sense of taste and smell within 3 months, an observational cohort study by McWilliams et al. found that after 2 years, 54.3% of individuals only partially recovered these senses, while 7.5% reported no recovery at all.¹¹ In a large single-institution study, Johnson et al. analyzed a wide array of potential predictors associated with smell and taste loss.¹² However, to the best of our knowledge, there appear to be no existing studies investigating comorbidities and social factors that influence recovery of smell and taste following loss due to COVID-19. In our study, we analyzed the 2021 National Health Interview Survey to identify predictors associated with loss and recovery of smell and taste after COVID-19 infection.

2 METHODS

3 RESULTS

There were 3844 respondents who reported testing positive for coronavirus/COVID-19. Of those who tested positive, 1963 (51.1%) and 1881 (48.9%) answered “Yes” to losing smell or taste, respectively, while 1692 (44.0%) individuals reported losing both smell and taste.

Of individuals who reported loss of smell, 1374 (70.0%) responded that they fully recovered their sense of smell, 505 (25.7%) reported partial recovery, while 83 (4.2%) reported no recovery at all. Among respondents who reported a loss of taste, 1403 (74.6%) responded that they fully recovered, 422 (22.4%) indicated partial recovery, while 54 (2.9%) reported no recovery (Table 1).

The mean age of respondents who reported a loss of smell or taste due to COVID-19 was 45 years in both groups. Females comprised 58.5% and 58.9% of respondents who lost their smell and taste, respectively. Younger age and female sex were both found to be significantly associated with loss of smell (p < .001) and loss of taste on univariate analysis (p < .001) (Table 1). Of respondents who reported a recovery of smell and taste, the mean age for “Fully recovered,” “Partially recovered,” and “Not recovered at all” was 44.1, 47.1, and 45.6, respectively (Table 2). The complete list of significant factors from the univariate analysis for COVID-19-related loss and recovery of smell and taste can be found in Tables 1 and 2. Factors found to be non-significant on univariate analysis are reported in Appendix S1.

For loss of smell due to COVID-19, older age (odds ratio [OR] 0.98; 95% confidence interval [CI] 0.98–0.99) and history of cancer (OR 0.75; 95% CI 0.56–1.00) were identified as protective factors (Table 3). Female sex (OR 1.38; 95% CI 1.17–1.64), Mexican ethnicity (OR 1.61; 95% CI 1.22–2.11), married with a spouse present (OR 1.21; 95% CI 1.02–1.43), history of e-cigarette use (OR 1.57; 95% CI 1.23–1.99), and severe COVID symptoms at worst (OR 15.29; 95% CI 10.08–23.21) were associated with higher odds of reporting a loss of smell (Table 3).

For loss of taste due to COVID-19, older age (OR 0.98; 95% CI 0.98–0.99) and a history of arthritis/RA/gout/lupus/fibromyalgia (OR 0.76; 95% CI 0.59–0.97) were identified as protective factors (Table 3). Female sex (OR 1.34; 95% CI 1.12–1.61), higher body mass index (BMI) (OR 1.02; 95% CI 1.01–1.04), severe COVID-19 symptoms at worst (OR 9.36; 95% CI 5.80–15.11), inability to smell (OR 11.24; 95% CI 7.48–16.89), and smell of unpleasant odor (OR 2.32; 95% CI 1.62–3.33) were associated with higher odds of reporting a loss of taste (Table 3).

For recovery of smell, younger age (OR 0.99; 95% CI 0.99–1.00) Black/African American race (OR 1.43; 95% CI 1.02–2.01), and non-Mexican Hispanic ethnicity (OR 1.53; 95% CI 1.01–2.33) were found to be associated with recovery. Female sex (OR 0.74; 95% CI 0.60–0.92), other self-reported race (excluding White, Black/African American, and Asian race) (OR 0.51; 95% CI 0.31–0.86), history of chronic liver condition (OR 0.31; 95% CI 0.12–0.79), history of anxiety disorder (OR 0.67; 95% CI 0.52–0.85), and severe COVID-19 symptom severity at worst (OR 0.64; 95% CI 0.48–0.85) were associated with a decreased likelihood of reporting a recovery of smell (Table 3).

For recovery of taste, older age (OR 0.98; 95% CI 0.97–0.99), female sex (OR 0.55; 95% CI 0.43–0.70), other self-reported race (excluding White, Black/African American, and Asian race) (OR 0.47; 95% CI 0.26–0.85), inability to smell (OR 0.22; 95% CI 0.15–0.33), and smell of unpleasant odor (OR 0.57; 95% CI 0.44–0.70) were associated with a decreased likelihood of reporting a recovery of smell (Table 3).

4 DISCUSSION

This is the first study to analyze a large national survey in order to determine factors associated with loss and recovery of smell and taste after COVID-19 infection in the United States. We identified various factors which may influence the loss and recovery of smell and taste after COVID-19 infection. Clinicians may use this information to counsel patients on healing expectations after experiencing sensory losses after COVID-19 infection.

Like previously published papers, our findings suggest female sex is associated with an increased likelihood of losing smell and taste due to COVID-19 and decreased odds of reporting recovery of smell and taste.^{5, 15-18} Although males may have higher exposure rates to certain infections, females may potentially have a heightened immune response compared with males due to differences in sex-chromosome-linked genes that regular immune function.^{19, 20} A more robust immune response can lead to increased disease symptom severity and injury to the olfactory nerves.

We found that older patients have a decreased likelihood of losing smell and taste, but also lower likelihood of recovering smell and taste once these senses are lost.^{12, 17, 18} Younger patients have better immunological function compared with older adults, which could be responsible for the improved recovery rates demonstrated in our analysis.^21-23 Despite the high prevalence of olfaction decay in the elderly population, no hypothesis has been established regarding the increased propensity for COVID-19 to alter olfaction at younger ages.²⁴ It is possible that younger populations are at an increased risk for exposure.

Additionally, our study identified that individuals of Mexican ethnicity may have an increased likelihood of olfactory dysfunction secondary to COVID-19. This might be attributed to the fact that Hispanic groups in the United States have a lower likelihood of seeking or receiving healthcare compared to the general population which might be due to lower health insurance coverage and language barriers.^25-27

History of e-cigarette use was also found to be associated with increased likelihood of losing smell due to COVID-19. This might be due to evidence suggesting that e-cigarette flavors and aerosol compounds reduce main olfactory epithelium (MOE) sensitivity through adaptation and cytotoxic damage to the barrier.^{28, 29} Disruption of MOE from e-cigarette use could exacerbate the loss of smell when in conjunction with a COVID-19 infection. Of note, a large number of survey respondents (18.3%) who reported testing positive for COVID-19 also reported current or previous use of an e-cigarette, highlighting the increased popularity of these devices in the United States.

A history of anxiety disorder may contribute to reduced rates of recovery after olfactory loss. Anxiety disorders have been previously recognized to exacerbate the immune system's response to COVID-19.³⁰ In addition, Speth et al. have hypothesized that emotional well-being disturbances might be secondary to central nervous system involvement of COVID-19.³¹ Further studies are needed to determine if anxiety stems directly from the coronavirus infection, QOL distress from loss of smell, or if the prior history of anxiety is responsible for worsened recovery rate.

Increasing BMI was found to be correlated with loss of taste in our study. There have been reports of pre-existing lower sensitivity for taste and decreased smell perception in obese patients compared to controls that could potentially confound virus-associated loss of either of these senses.^32-35 Nonetheless, it has been hypothesized that COVID-19 induced dysregulations in ghrelin and leptin, and inflammation involving IL-6 and TNF-α, are responsible for the dysregulated immune response which may result in decreased loss of taste perception.^36-38

By contrast, higher income and history of inflammatory musculoskeletal (MSK) disorders may be associated with decreased odds of losing taste. As might be expected, higher income could allow for more flexibility to get tested and treated sooner due to job stability and the likelihood of having medical insurance, resulting in reduced disease severity and sensory dysfunction. The association between MSK disorders and reduced rates of smell loss may be due to the prevalence of anti-inflammatory medications, such as corticosteroids, used to treat inflammatory MSK disorders. As an indirect effect, the user may experience benefits from the neuroprotective and anti-inflammatory actions, thus potentially reducing the likelihood of report loss of taste.³⁹

This cross-sectional national database study is subject to several limitations. The absence of patient-level data means that there are many clinical data points we could not capture, including differences in medical history and medication use, which could explain variations in sensory dysfunction between individuals. Due to the cross-sectional nature of this study, we are also unable to establish causality to determine direct relationships between COVID-19 and the loss or recovery of smell and taste. Additionally, as with any survey, there is potential for selection bias that occurs if the sample population is not an accurate representation of the broader population. As a result, data might be skewed or unrepresentative. Another limitation is our inability to provide temporal data that would allow us to identify the recovery rate between COVID-19 diagnosis, initial presentation of gustatory and olfactory dysfunction, and the onset of recovery. Although we are unable to provide information on the recovery timeline and its variability with individual predictors, other research groups have found general individual recovery rate timelines for smell and taste dysfunction.^{15, 40} Lastly, the self-reported data from the national database survey is inherently limited to recall bias and social desirability bias. The data may have potential inaccuracies, which can lead to underreporting or overreporting of certain survey responses.

5 CONCLUSION

This is the first study to analyze a large national survey in order to identify patient characteristics associated with loss and recovery of smell and taste after COVID-19 infection. Factors including sex, age, ethnicity, BMI, income, as well as history of anxiety and e-cigarette use may influence sensory dysfunction after infection with SARS-CoV-2, and clinicians may use this information to counsel patients on healing expectations after experiencing sensory losses. This improved guidance can be crucial for patient care, as the impact of losing smell and taste can significantly affect QOL and patient well-being.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.