Study measures recovery rate of SARS-CoV-2-induced olfactory loss

In a recent study posted to the medRxiv* preprint server, an interdisciplinary team of researchers from the Washington University, United States (US), estimated the trajectory of coronavirus disease 2019 (COVID-19)-induced olfactory loss over six months duration and assessed predictive features related to the recovery of olfactory function.

Study: Natural Trajectory of Recovery of COVID-19 Associated Olfactory Loss. Image Credit: E.Va/ShutterstockStudy: Natural Trajectory of Recovery of COVID-19 Associated Olfactory Loss. Image Credit: E.Va/Shutterstock

Studies have shown an increased prevalence of olfactory dysfunction (approximately 34% to 86%) in COVID-19 patients resulting in olfactory function loss. An estimated 44% to 64% of COVID-19 patients experienced recovery of olfactory function post two weeks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, limited data is available for the percentage of patients who experience persistent olfactory loss even after six months following SARS-CoV-2 infection.

Study design

In the current study, patients in the first two weeks of a SARS-CoV-2 infection and an indicated olfactory loss during COVID-19 questionnaire screening were identified by the electronic health record (EHR) and enrolled. Participants were requested to do self-assessments of complete olfactory function every 30 days for a period of six months or until complete recovery. The participants were assessed using Clinical Global Impression (CGI) and the University Of Pennsylvania Smell Identification Test (UPSIT).

The CGI is a Likert subjective rating scale that measured severity [(CGI-S); rated from 0 to 7] and improvement [(CGI-I); rated from 1-7]. While the UPSIT is a “scratch and sniff” objective test with high internal variability and contained four booklets impregnated with different odors, each having 10 questions of forced choice. Scores achieved were classified into five different categories: normosmia, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia.

No specific treatment interventions were provided during the assessment and participants were instructed to wait and watch for spontaneous recovery and submit answers during monthly surveys. Study data was collated and managed by a secure web-based application- Research Electronic Data Capture (REDCap) hosted at the University of Washington.

The relationship between demographic and clinical parameters with recovery time for olfactory loss was estimated using Cox-Proportional Hazards regression. Log-log survival plots were used to check assumptions of proportional hazards. The team used conjunctive consolidation to develop a staging system for clinical severity. This staging system so developed predicted the likelihood of persistent olfactory dysfunction.

Findings

The researchers observed that at the baseline using UPSIT olfactory assessment, 36%, 31%, 18%, and 14% of study participants had severe, moderate, mild, and normal hyposmia, respectively. Only 2% of study participants reported initiation of anosmia treatment.

Among the study participants in the acute period, the researchers observed a self-reported recovery rate of 57%, 71%, and 81% in the olfactory loss by one month, second month, and six months, respectively, following SARS-CoV-2-positive test results.

The findings suggested that among participants who had an olfactory loss at enrolment time, the probability of complete subjective recovery as per the criteria of CGI-S was 43% and 58% at two and six months, respectively, while according to the CGI-I criteria it was 57% and 84%, respectively.

Similarly, the probability of objective complete recovery among participants as per UPSIT criteria at two and six months was 28% and 44%, respectively, while the probability of partial recovery as per these criteria was 20% and 56%, respectively.

The researchers demonstrated a confirmed association between olfactory loss recovery and age [adjusted hazard ratio (aHR) age <50years = 8.1 (95% confidence interval (CI) 1.1 to 64.1)], and the severeness of olfactory loss at baseline [aHRMild Loss 6.2 (95% CI 1.2 to 33.0)] by cox-proportional hazards.

For the assessment of persistent olfactory disorder, researchers developed a new staging system for clinical severity having three categories: good (33%), fair (54%), and poor (91%). On performing regression analysis, the researchers observed that in the good and fair category the likelihood of olfactory function recovery was nearly 10 times [(HR=10.9 (95% CI 1.9 to 62.6)] and five times [HR=5.5 (95% CI 1.1 to 27.4)] greater, respectively, as compared to the poor category.

Conclusion

The findings of this study demonstrated that a large number of participants experienced rapid recovery of olfactory loss within two to three weeks of SARS-CoV-2 infection. After six months of infection, 81% of participants had recovered from olfactory loss based on self-report. The likelihood of olfactory function recovery was reduced with increasing age and anosmia severity at baseline. 

The results of this study can be utilized for common decision-making with the patients associated with olfactory function recovery post-COVID-19 infection. Further, the authors suggested future interventions for the modification of current therapies like olfactory training and new therapy development for anosmia treatment. They warrant the need to estimate the recovery rate of olfactory loss beyond six months. However, the study has limitations which include the chances of ascertainment bias, lack of parosmia and phantosmia measurement, and the exclusion of hospitalized patients.

*Important notice

medRxiv 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:
Sangeeta Paul

Written by

Sangeeta Paul

Sangeeta Paul is a researcher and medical writer based in Gurugram, India. Her academic background is in Pharmacy; she has a Bachelor’s in Pharmacy, a Master’s in Pharmacy (Pharmacology), and Ph.D. in Pharmacology from Banasthali Vidyapith, Rajasthan, India. She also holds a post-graduate diploma in Drug regulatory affairs from Jamia Hamdard, New Delhi, and a post-graduate diploma in Intellectual Property Rights, IGNOU, India.

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