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
We found two small studies to include in the review, including a total of 30 people. All participants 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 one study was a course of corticosteroid tablets ('systemic') and nasal irrigation (with a wash consisting of a mix of corticosteroids, decongestant and an agent that breaks down mucus). The second study used a course of a supplement known as palmitoylethanolamide and luteolin.
Systemic corticosteroids and nasal irrigation (intranasal corticosteroids/decongestant/mucolytic) compared to no treatment
We do not know whether corticosteroid 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 one study was identified and it included a small number of patients.
Palmitoylethanolamide and luteolin compared to no treatment
We do not know whether palmitoylethanolamide and luteolin is better or worse than no treatment at:
- restoring the sense of smell back to normal after 30 days;
- changing the sense of smell after 30 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 one study was identified and it 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 corticosteroids with nasal irrigation, or using a palmitoylethanolamide and luteolin supplement, might treat problems with the sense of smell after COVID-19, or whether these treatments can potentially cause 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 October 2021.
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 a number of ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.
Olfactory dysfunction is a common consequence of COVID-19 infection and persistent symptoms can have a profound impact on quality of life. At present there is little guidance on how best to treat this condition. A variety of interventions have been suggested to promote recovery, including medication and olfactory training. However, it is uncertain whether any intervention is of benefit. This is an update of the 2021 review with one additional study added.
1) To evaluate the benefits and harms of any intervention versus no treatment for people with persisting olfactory dysfunction due to COVID-19 infection.
2) To keep the evidence up-to-date, using a living systematic review approach.
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the latest search was 20 October 2021.
We included randomised controlled trials (RCTs) in people with COVID-19 related olfactory disturbance that had persisted for at least four weeks. We included any intervention compared to no treatment or placebo.
We used standard Cochrane methods. Our 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.
We included two studies with 30 participants. The studies evaluated the following interventions: systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant and palmitoylethanolamide plus luteolin.
Systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant compared to no intervention
We included a single RCT with 18 participants who had anosmia for at least 30 days following COVID-19 infection. Participants received a 15-day course of oral corticosteroids combined with nasal irrigation (consisting of an intranasal corticosteroid/mucolytic/decongestant solution) or no intervention. Psychophysical testing was used to assess olfactory function at 40 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results.
Palmitoylethanolamide plus luteolin compared to no intervention
We included a single RCT with 12 participants who had anosmia or hyposmia for at least 90 days following COVID-19 infection. Participants received a 30-day course of palmitoylethanolamide and luteolin or no intervention. Psychophysical testing was used to assess olfactory function at 30 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results.