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

Why this is important

The sense of smell is critical to one's enjoyment of odours and tastes, and is important for safety. During the COVID-19 pandemic there has been an increasing focus on change in sense of smell as one of the early symptoms associated with infection. This can be a reduction, change or complete loss of the sense of smell. For most people this is temporary, however for some this lasts weeks or even months. If a person has lost their sense of smell for a long time (over four weeks after having COVID-19), we do not know if there are any treatments that might help it to recover. 

How we identified and assessed the evidence

We searched the medical literature, identifying relevant studies and summarising the results. We assessed the quality of the studies as well as the certainty of the evidence. Factors influencing this included the size of the studies, the methods used to perform them and how results were reported by researchers. Based on this, we classed the evidence as being of very low, low, moderate or high certainty.

What we found

The only complete study we found included 18 people. All patients had problems with their sense of smell that had lasted for at least four weeks, and started after a COVID-19 infection. Problems with the sense of smell were identified using special smell identification tests carried out by the research team. The patients were randomly divided into two groups: those who would receive treatment and those who would not. The treatment in this case was a course of steroid tablets, given with a nasal spray (consisting of a mix of steroids, decongestant and an agent that breaks down mucus). The researchers followed them for 40 days and the results are presented below:

Systemic corticosteroids and nasal irrigation (intranasal corticosteroids/decongestant/mucolytic) compared to no treatment

We do not know whether steroid tablets with nasal irrigation is better or worse than no treatment at:

 - restoring the sense of smell back to normal after 40 days;
 - changing the sense of smell after 40 days;
 - causing any unwanted side effects.

This is because the evidence that we found was of very low certainty, mainly due to the fact that only study was identified and included a small number of patients.

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

What this means

It is unclear whether using steroids with nasal irrigation treats problems with the sense of smell after COVID-19, or whether it can potentially cause any harm.

Other treatments are under investigation. 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 available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified other ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.

For this (first) version of the living review we identified only one study with a small sample size, which assessed systemic steroids and nasal irrigation (intranasal steroid/mucolytic/decongestant). However, the evidence regarding the benefits and harms from this intervention to treat persistent post-COVID-19 olfactory dysfunction is very uncertain.

Read the full abstract...
Background: 

Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can have a profound effect on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction, however several strategies have been proposed from the evidence relating to the treatment of post-viral anosmia (such as medication or olfactory training).

Objectives: 

To assess the effects (benefits and harms) of interventions that have been used, or proposed, to treat 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. Only individuals who had symptoms for at least 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. Primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia 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 with 18 participants, which compared the use of a 15-day course of oral steroids combined with nasal irrigation (consisting of an intranasal steroid/mucolytic/decongestant solution) with no intervention. Psychophysical testing was used to assess olfactory function at baseline, 20 and 40 days.

Systemic corticosteroids plus intranasal steroid/mucolytic/decongestant compared to no intervention

Recovery of sense of smell was assessed after 40 days (25 days after cessation of treatment) using the Connecticut Chemosensory Clinical Research Center (CCCRC) score. This tool has a range of 0 to 100, and a score of ≥ 90 represents normal olfactory function. The evidence is very uncertain about the effect of this intervention on recovery of the sense of smell at one to three months (5/9 participants in the intervention group scored ≥ 90 compared to 0/9 in the control group; risk ratio (RR) 11.00, 95% confidence interval (CI) 0.70 to 173.66; 1 study; 18 participants; very low-certainty evidence).

Change in sense of smell was assessed using the CCCRC score at 40 days. This study reported an improvement in sense of smell in the intervention group from baseline (median improvement in CCCRC score 60, interquartile range (IQR) 40) compared to the control group (median improvement in CCCRC score 30, IQR 25) (1 study; 18 participants; very low-certainty evidence).

Serious adverse events and other adverse events were not identified in any participants of this study; however, it is unclear how these outcomes were assessed and recorded (1 study; 18 participants; very low-certainty evidence).