Interventions for the prevention of persistent smell disorders (olfactory dysfunction) after COVID-19 infection

Why this is important

COVID-19 has been found to cause problems with the sense of smell. Sometimes this is a reduction in the ability to smell things, and sometimes it is a complete loss of the sense of smell. For many people this recovers in a short time, but for others it may last for weeks or months. This review considers whether there are treatments that people might take as soon as they have lost their sense of smell (within four weeks of the symptoms starting), to try and stop this becoming a long-standing problem.

How we identified and assessed the evidence

We searched for all relevant studies in the medical literature to summarise the results. We also looked at how certain the evidence was, considering things like the size of the studies and how they were carried out. Based on this, we classed the evidence as being of very low, low, moderate or high certainty.

What we found

We only found one study that had been completed. This included 100 people, all of whom had problems with their sense of smell for a short time (less than four weeks) at the start of the study. The study compared people who were treated with a steroid spray that goes into the nose, with people who were given no treatment. All of the people in the study were also recommended to carry out 'olfactory training' – to spend a short time each day practising smelling particular scents, to try and stimulate their sense of smell to return. The researchers followed them for three weeks to see what happened. The findings from this one comparison are presented here:

Intranasal corticosteroids compared to no treatment (all using olfactory training)

We do not know whether a nasal steroid spray is better or worse than no treatment at:

- making people feel that their sense of smell is back to normal after three weeks; 
- resulting in a change in the sense of smell after three weeks.

This is because the evidence was of very low certainty.

We did find a number of other studies that are being carried out, but no results from these studies were available yet to be included in this review.

What this means

We do not know whether using a nasal steroid spray has any benefit in preventing longer-term loss of the sense of smell that is related to COVID-19, or whether it causes any harm. We do not have any evidence about other treatments. This review is a 'living systematic review' - meaning that we will keep checking for new studies that might be relevant, and the review will be continually updated when any extra results are available.

How up-to-date is this review?

The evidence in this Cochrane Review is current to December 2020.

Authors' conclusions: 

There is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following COVID-19 infection. However, we have identified a small number of additional ongoing studies in this area. 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. 

Read the full abstract...
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 strategy: 

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).