Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.BACKGROUND
 Loss of olfactory function is well recognised as a cardinal symptom of COVID-19 infection, and the ongoing pandemic has resulted in a large number of affected individuals with abnormalities in their sense of smell.  For many, the condition is temporary and resolves within two to four weeks.  However, in a significant minority the symptoms persist.  At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recovery and prevent persisting olfactory disturbance.   OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID-19 infection.  A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.   SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies.  The date of the search was 16 December 2020.


 SELECTION CRITERIA
 Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection.  Individuals who had symptoms for less than four weeks were included in this review.  Studies compared any intervention with no treatment or placebo.   DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures.  Our primary outcomes were the presence of normal olfactory function, serious adverse effects and change in sense of smell.  Secondary outcomes were the prevalence of parosmia, change in sense of taste, disease-related quality of life and other adverse effects (including nosebleeds/bloody discharge).  We used GRADE to assess the certainty of the evidence for each outcome.   MAIN RESULTS: We included one study of 100 participants, which compared an intranasal steroid spray to no intervention.  Participants in both groups were also advised to undertake olfactory training for the duration of the trial.  Data were identified for only two of the prespecified outcomes for this review, and no data were available for the primary outcome of serious adverse effects.  Intranasal corticosteroids compared to no intervention (all using olfactory training) Presence of normal olfactory function after three weeks of treatment was self-assessed by the participants, using a visual analogue scale (range 0 to 10, higher scores = better).  A score of 10 represented "completely normal smell sensation".  The evidence is very uncertain about the effect of intranasal corticosteroids on self-rated recovery of sense of smell (estimated absolute effect 619 per 1000 compared to 520 per 1000, risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; very low-certainty evidence).   Change in sense of smell was not reported, but the self-rated score for sense of smell was reported at the endpoint of the study with the same visual analogue scale (after three weeks of treatment).  The median scores at endpoint were 10 (interquartile range (IQR) 9 to 10) for the group receiving intranasal corticosteroids, and 10 (IQR 5 to 10) for the group receiving no intervention (1 study; 100 participants; very low-certainty evidence).


 AUTHORS' CONCLUSIONS
 There is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following COVID-19 infection.  As this is a living systematic review, the evidence will be updated regularly to incorporate new data from these, and other relevant studies, as they become available.   For this (first) version of the living review, we identified a single study of intranasal corticosteroids to include in this review, which provided data for only two of our prespecified outcomes.  The evidence was of very low certainty, therefore we were unable to determine whether intranasal corticosteroids may have a beneficial or harmful effect.
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