TLDR: Objective olfactory dysfunction 1-3 months after COVID-19 predicts post-COVID condition (PCC) and reduced quality of life after one year, while subjective symptoms do not.
Highlights:
- Individuals with objectively measured olfactory dysfunction shortly after COVID-19 are more likely to develop long-term health issues and reduced quality of life a year later.
- Those with post-COVID condition (PCC) often score lower on cognitive tests and report higher levels of fatigue.
- Early olfactory testing can help identify those at risk for prolonged symptoms and diminished quality of life post-COVID.
- Subjective reports of smell loss are not reliable predictors of long-term outcomes compared to objective measures.
Source: Brain & Behavior (2024)
Olfactory Dysfunction & COVID-19: Mechanisms of Connection
Olfactory dysfunction, including hyposmia (reduced sense of smell), anosmia (loss of smell), and parosmia (distorted sense of smell), has emerged as a common symptom among COVID-19 patients.
This sensory impairment can occur during the acute phase of infection and persist for months, impacting the quality of life.
Direct Viral Damage
SARS-CoV-2, the virus causing COVID-19, can infect the olfactory epithelium, the tissue responsible for smell detection.
The virus enters cells via the ACE2 receptor, which is abundant in the nasal mucosa, potentially leading to cell damage and olfactory dysfunction.
Inflammation & Immune Response
The infection triggers an inflammatory response in the nasal cavity.
Cytokines and other inflammatory mediators can cause swelling and blockage, impairing the function of olfactory receptor neurons.
Prolonged inflammation may damage these neurons and the surrounding support cells, leading to persistent smell loss.
Olfactory Bulb Involvement
The olfactory bulb, a brain structure processing smell information, can be affected by the viral infection.
Studies have shown changes in the olfactory bulb’s structure and function in COVID-19 patients, which may contribute to olfactory dysfunction.
Neuroinvasion & Central Nervous System Impact
There is evidence that SARS-CoV-2 might reach the brain via the olfactory pathway, potentially causing broader neurological impacts.
This neuroinvasion could contribute to smell disorders and other neurological symptoms observed in COVID-19 patients.
Regeneration & Recovery
The olfactory epithelium has regenerative capabilities.
However, severe or prolonged damage due to COVID-19 may hinder the regeneration process.
The extent and speed of recovery can vary, with some patients experiencing partial or complete return of smell, while others suffer long-term deficits.
Main Findings: Olfactory Dysfunction & Post-COVID Condition (2024)
1. Objective Olfactory Dysfunction as a Predictor
Objective Testing
The study found that objectively measured olfactory dysfunction (using a standardized test) 1-3 months after COVID-19 infection was a strong predictor of post-COVID condition (PCC) and reduced health-related quality of life (HRQoL) one year later.
This means that people who had measurable smell loss were more likely to experience ongoing health issues.
Subjective Symptoms Unreliable
In contrast, individuals’ self-reported smell loss did not reliably predict these long-term outcomes.
This highlights the importance of objective testing over self-assessment.
2. Cognitive and Fatigue Differences
Cognitive Impairment
The study observed that those with PCC scored worse on cognitive tests.
Specifically, 61.5% of the PCC group had scores indicating mild cognitive impairment, compared to 21.7% in the non-PCC group.
This suggests that cognitive issues are more prevalent among those with PCC.
Fatigue Levels
Participants with PCC reported higher levels of fatigue across various dimensions (general, physical, mental) compared to those without PCC.
They showed significantly higher scores on the Multidimensional Fatigue Inventory, indicating more severe and widespread fatigue.
3. Health-Related Quality of Life (HRQoL)
Persistent Symptoms
At the one-year follow-up, a significant number of participants (68.2%) reported at least one lingering symptom.
Common issues included concentration difficulties, physical fatigue, and neurological symptoms like impaired memory and mental fatigue.
Quality of Life
Those with PCC were more likely to report reduced HRQoL, with issues such as pain, discomfort, and difficulty performing usual activities.
A significant proportion also rated their overall health poorly.
4. Olfactory Dysfunction Details
Degree of Dysfunction
Among those tested, 6.1% had anosmia (complete loss of smell), 31.8% had hyposmia (reduced smell), and the rest had a normal sense of smell.
The PCC group had a significantly higher rate of olfactory dysfunction (69.2%) compared to the non-PCC group (32.6%).
Predictive Value
The intensity of the smell test results (using n-butanol) correlated negatively with PCC and symptoms like neurological issues and lower HRQoL.
This suggests that poorer smell test performance was associated with worse outcomes.
Study Details: Olfactory Symptoms & Long Covid Syndrome (2024)
Sample
- Participants: The study included a total of 66 individuals, both hospitalized (N = 10) and non-hospitalized (N = 56).
- Follow-up: Participants were evaluated 1–3 months after infection, with follow-up data collected one year post-infection.
Methods
Olfactory Testing
- Objective Measurement: Participants underwent an olfactory threshold test using n-butanol to objectively measure their sense of smell.
- Assessment: Both a threshold and a supra-threshold assessment were conducted to evaluate olfactory function.
Neuropsychological Testing
- Montreal Cognitive Assessment (MoCA): Used to screen for global cognitive function and detect mild cognitive impairment.
- Additional Tests: Included assessments of verbal learning, episodic memory, working memory, speed, and attention using standardized tests from the Repeatable Battery for the Assessment of Neuropsychological Status and the Wechsler Adult Intelligence Scale IV.
Health-Related Quality of Life
- Questionnaires: Participants completed a custom questionnaire for persistent symptoms and the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire to assess HRQoL.
Data Analysis
- Principal Component Analysis (PCA): Used to identify predictors for PCC at one year.
- Statistical Tests: Included Mann-Whitney U-test, Fisher’s exact test, and multivariable logistic regression to analyze the data.
Limitations
- Sample Size: The study had a relatively small cohort size, which may limit the generalizability of the findings.
- Pre-COVID Cognitive Data: The lack of pre-COVID cognitive test results made it challenging to determine the baseline cognitive function of participants.
- Follow-up Assessments: The study did not include repeated follow-up olfactory and cognitive assessments, which could have provided a better understanding of the dynamics of symptoms and impairments over time.
- Demographic Homogeneity: The cohort had a high level of education, which might have influenced the neurocognitive test results. Additionally, the study was conducted in a specific geographic region, potentially limiting the applicability of the findings to broader populations.
Conclusion: Olfactory Dysfunction & Post-Acute COVID
This study demonstrated that objectively measured olfactory dysfunction in the early post-acute phase of COVID-19 is a significant predictor of long-term health issues, including post-COVID condition (PCC) and reduced health-related quality of life (HRQoL).
Unlike subjective reports of smell loss, objective olfactory testing provided a reliable indicator of those at higher risk for persistent symptoms and cognitive impairment.
Participants with PCC also exhibited more pronounced fatigue and cognitive deficits, underscoring the multifaceted impact of COVID-19 on long-term health.
Despite the study’s limitations, such as a small sample size and lack of pre-COVID cognitive data, the findings emphasize the importance of early olfactory screening as part of post-acute care for COVID-19 patients.
By identifying individuals at risk for long-term complications, healthcare providers can better target interventions and support to improve patient outcomes.
Further research with larger cohorts and repeated assessments is necessary to validate these findings and refine prognostic tools for post-COVID syndrome.
References
- Study: Olfactory dysfunction as an early predictor for post-COVID condition at 1-year follow-up (2024)
- Authors: Christoffer Granvik et al.
