Loss of smell following COVID-19 recovery: How long could it last?

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In a recent study posted to the Preprints with The Lancet* server, researchers in China conducted a multi-center, retrospective study to gather data on the prevalence of olfactory dysfunction (OD) after three years of recovering from coronavirus disease 2019 (COVID-19).

Study: Persisting Olfactory Impairments in Recovered COVID-19 Patient: A Three-Year Follow-Up. Image Credit: Microgen / ShutterstockStudy: Persisting Olfactory Impairments in Recovered COVID-19 Patient: A Three-Year Follow-Up. Image Credit: Microgen / Shutterstock

*Important notice: Preprints with The Lancet / SSRN publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

OD, or loss of smell, is among the most common post-acute sequelae of COVID (PASC), which studies have shown also persists one or two years after disease onset. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the human host from the nasal cavity to establish infection by interacting with angiotensin-converting enzyme 2 (ACE2) receptors.

Studies have found that people with more ACE2 expression in their olfactory epithelium are prone to infection and developing OD later.

In most cases, this issue gradually fades away. However, in some cases, its long-term persistence affects the life of patients. For instance, some OD patients experience severe shortness of breath. Previous studies have not determined when an individual with persistent OD recovers from this peculiar condition and their clinical characteristics. Assessment of these variables for patients with OD could help counsel and treat them in time.

About the study

In the present study, researchers performed a detailed survey among 167 people, of which 155 had recovered from COVID-19 before April 1, 2020, and the remaining 170 were age-matched healthy controls in Wuhan, China. These patients met the prespecified recovery criteria.

They had normal body temperature for at least three days, no respiratory symptoms, and two sequential reverse transcription-polymerase chain reaction (RT-PCR) tests confirmed their COVID-19-negative status.

The team collected demographic, epidemiological, and clinical symptoms data face-to-face. However, they resolved the ambiguity in data, if any, over a telephone call. For other evaluations, they relied on the scores of specific tests, e.g., a score of six or more on the Hamilton Depression Scale (HAMD) and Anxiety Scale (HAMA) indicated a patient was depressed and anxious. Likewise, they used Athens Insomnia Scale (AIS) to assess sleep disturbances among the study participants.

The researchers used Toyota‐Takagi (T&T) olfactometry scores system for olfactory testing, which used five odors, pineapple, mint, garlic, rose, and ginger, for olfactory sensitivity measurements. In a week, they tested each study participant twice, and the median of the recognition field indicated whether their olfactory function was normal. Finally, the team made statistical comparisons between the study and control groups.

For continuous variables, they performed the Mann–Whitney U test and Fisher's exact test for categorical variables. A logistic regression model helped them identify all OD-related factors, while, in a multivariable analysis, a p-value cutoff of 0.05 helped them identify significant predictors by forward elimination.

Results

The researchers remarkably followed up COVID-19 recovered patients for 36 months (three years) after infection. They made three significant findings. First, they found that >95% of patients restored normal olfactory function by the third year after COVID-19 recovery, assessed via T&T tests. Second, they found that insomnia increased the risk of persistent hyposmia. Third, patients with anxiety are more likely to experience loss of smell in the long term.

In addition, among patients who recovered from COVID-19 three years ago, 10 to 15% had anxiety and depression, and 30% to 50% had sleeping disorders.

Another remarkable observation was that although only 4.5% of the study participants had persistent OD, none had anosmia or complete loss of smell. Another long-term follow-up study by Boscolo Rizzo et al. reported persistent OD in 11.8% of the study participants during a two-year follow-up.

The observed lower rate of OD in this study confirms that this condition gradually fades away in most cases, though additional factors might also be at play. For instance, the SARS-CoV-2 variant that caused the initial infection might be behind varying OD incidence across different populations.

Of 155 COVID-19-recovered patients constituting the study population, 80.6% were in the 50 to 70 years age group, and it is well-recognized that aging degenerates olfactory sensitivity. However, the results showed no statistically significant association between persistent OD and age, general COVID-19 symptoms, or therapies, except for female dependence.

Thus, the authors noted that while headache and anosmia were correlated, the headache and OD were not. Consistent with previous findings, they also noted that insomnia might be a risk factor for OD in COVID-19 patients, especially those with AIS scores ≥6.

Conclusion

Overall, the study results suggested that though it might take time, up to three years in most cases, COVID-19 patients recover from olfactory dysfunction. Based on observed high OD recovery rates, the researchers reassured patients with SARS-COV-2 infection of a good prognosis.

*Important notice: Preprints with The Lancet / SSRN publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Neha Mathur

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.

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