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 found five studies that had been completed.
Intranasal corticosteroids compared to no treatment
Three studies looked at this treatment.
Nasal corticosteroid spray might make little or no difference to the sense of smell when measured with specific tests (rather than when asking people about their sense of smell).
The rest of the evidence was of very low certainty, so we do not know whether a nasal corticosteroid spray is better or worse than no treatment at:
- helping the sense of smell get back to normal (either people feeling that their sense of smell is back to normal, or having a normal sense of smell according to specific tests);
- making people feel that their sense of smell has improved;
- causing any unwanted side effects.
Intranasal corticosteroid drops compared to placebo (dummy treatment)
One study looked at this treatment.
Intranasal corticosteroid drops might not make any difference to the number of people who think their sense of smell has recovered at 30 days.
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 corticosteroid spray or nasal drops has any benefit in preventing longer-term loss of the sense of smell that is related to COVID-19, or whether they may cause any harm. 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 preventing 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.
Loss of olfactory function is well recognised as a symptom of COVID-19 infection, and the pandemic has resulted in a large number of 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. This is an update of the 2021 review with four studies added.
1) To evaluate the benefits and harms of any intervention versus no treatment for people with acute 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, which had been present for less than four weeks. We included any intervention compared to no treatment or placebo.
We used standard Cochrane methods. 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.
We included five studies with 691 participants. The studies evaluated the following interventions: intranasal corticosteroid sprays, intranasal corticosteroid drops, intranasal hypertonic saline and zinc sulphate.
Intranasal corticosteroid spray compared to no intervention/placebo
We included three studies with 288 participants who had olfactory dysfunction for less than four weeks following COVID-19.
Presence of normal olfactory function
The evidence is very uncertain about the effect of intranasal corticosteroid spray on both self-rated recovery of olfactory function and recovery of olfactory function using psychophysical tests at up to four weeks follow-up (self-rated: risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; psychophysical testing: RR 2.3, 95% CI 1.16 to 4.63; 1 study; 77 participants; very low-certainty evidence).
Change in sense of smell
The evidence is also very uncertain about the effect of intranasal corticosteroid spray on self-rated change in the sense of smell (at less than 4 weeks: mean difference (MD) 0.5 points lower, 95% CI 1.38 lower to 0.38 higher; 1 study; 77 participants; at > 4 weeks to 3 months: MD 2.4 points higher, 95% CI 1.32 higher to 3.48 higher; 1 study; 100 participants; very low-certainty evidence, rated on a scale of 1 to 10, higher scores mean better olfactory function). Intranasal corticosteroids may make little or no difference to the change in sense of smell when assessed with psychophysical testing (MD 0.2 points, 95% CI 2.06 points lower to 2.06 points higher; 1 study; 77 participants; low-certainty evidence, 0- to 24-point scale, higher scores mean better olfactory function).
Serious adverse effects
The authors of one study reported no adverse effects, but their intention to collect these data was not pre-specified so we are uncertain if these were systematically sought and identified. The remaining two studies did not report on adverse effects.
Intranasal corticosteroid drops compared to no intervention/placebo
We included one study with 248 participants who had olfactory dysfunction for ≤ 15 days following COVID-19.
Presence of normal olfactory function
Intranasal corticosteroid drops may make little or no difference to self-rated recovery at > 4 weeks to 3 months (RR 1.00, 95% CI 0.89 to 1.11; 1 study; 248 participants; low-certainty evidence). No other outcomes were assessed by this study.
Data on the use of hypertonic saline nasal irrigation and the use of zinc sulphate to prevent persistent olfactory dysfunction are included in the full text of the review.