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Webster, Katie E., O'Byrne, Lisa, MacKeith, Samuel, Philpott, Carl 
ORCID: https://orcid.org/0000-0002-1125-3236, Hopkins, Claire and Burton, Martin J.
(2022)
Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.
Cochrane Database of Systematic Reviews, 2022 (9).
ISSN 1465-1858
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Abstract
Background: 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. Objectives: 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. Search methods: 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Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials.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. Selection criteria: 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. Data collection and analysis: 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. Main results: 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. Authors' conclusions: 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.
| Item Type: | Article |
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| Additional Information: | Funding Information: No financial support was reported for the study Funding Information: This project was also supported by the National Institute for Health Research, via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to Cochrane ENT. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Evidence Synthesis Programme, NIHR, NHS or the Department of Health. Funding Information: This review forms part of NIHR132103 - The prevention and treatment of persisting olfactory dysfunction following COVID-19 infection; a suite of Cochrane living systematic reviews. This study is one of a number of COVID-19 studies that have been funded by the National Institute for Health Research (NIHR) as part of its Recovery and Learning call, totalling £5.5m in funding, to help better manage current and future waves of the COVID-19 pandemic and investigate its long-term impact on the health and care system beyond the acute phase. This project was also supported by the National Institute for Health Research, via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to Cochrane ENT. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Evidence Synthesis Programme, NIHR, NHS or the Department of Health. Lisa O' Byrne, Evidence Synthesis Ireland Fellow, was part-supported by the Health Research Board (Ireland) and the HSC Public Health Agency (Grant number CBES-2018-001) through Evidence Synthesis Ireland/Cochrane Ireland. The authors would like to extend their sincere thanks to the board members of AbScent and Fifth Sense for their insights and significant contributions to the development of this protocol. We would also like to thank the many individuals affected by smell loss who took the time to complete our surveys, which were invaluable when prioritising outcomes for this review. The authors would like to acknowledge Lee Yee Chong for her work on generic methods content, some of which has been adapted for use in this review (with permission). The authors are grateful to Joanne Abbott, Information Specialist with Cochrane Pain, Palliative and Supportive Care, for providing peer review comments on the draft search methods, and Iris Gordon, Information Specialist with Cochrane Eyes & Vision, for providing peer review comments on the update search methods introduced in July 2021. Lastly, we would like to thank Professor Peter Tugwell, Senior Editor Cochrane MOSS Network, for acting as sign-off editor for the initial version of this review and Professor Richard Harvey, Cochrane ENT Editor, for acting as sign-off editor for the August 2022 update. Cochrane ENT supported the authors in the development of this review. The following people conducted the editorial process for this article: Sign-off Editor (final editorial decision): Professor Peter Tugwell, Senior Editor Cochrane MOSS Network (initial version) and Professor Richard Harvey, Cochrane ENT Editor (2022 update). Managing Editor (selected peer reviewers, collated peer reviewer comments, provided editorial guidance to authors, edited the article): Jenny Bellorini, Cochrane ENT Copy Editor (copy editing and production): Jenny Bellorini, Cochrane ENT Peer reviewers (provided comments and recommended an editorial decision): Richard Rosenfeld and Richard Harvey, Cochrane ENT Editors (clinical/content review); Emma Jackson, Cochrane Airways (consumer review); Iris Gordon, Information Specialist, Cochrane Eyes & Vision (search review). One additional peer reviewer provided clinical peer review, but chose not to be publicly acknowledged. Sign-off Editor (final editorial decision): Professor Peter Tugwell, Senior Editor Cochrane MOSS Network (initial version) and Professor Richard Harvey, Cochrane ENT Editor (2022 update). Managing Editor (selected peer reviewers, collated peer reviewer comments, provided editorial guidance to authors, edited the article): Jenny Bellorini, Cochrane ENT Copy Editor (copy editing and production): Jenny Bellorini, Cochrane ENT Peer reviewers (provided comments and recommended an editorial decision): Richard Rosenfeld and Richard Harvey, Cochrane ENT Editors (clinical/content review); Emma Jackson, Cochrane Airways (consumer review); Iris Gordon, Information Specialist, Cochrane Eyes & Vision (search review). One additional peer reviewer provided clinical peer review, but chose not to be publicly acknowledged. Funding Information: Lisa O' Byrne, Evidence Synthesis Ireland Fellow, was part-supported by the Health Research Board (Ireland) and the HSC Public Health Agency (Grant number CBES-2018-001) through Evidence Synthesis Ireland/Cochrane Ireland. Publisher Copyright: Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. |
| Uncontrolled Keywords: | pharmacology (medical) ,/dk/atira/pure/subjectarea/asjc/2700/2736 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Respiratory and Airways Group Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 13 Oct 2022 09:33 |
| Last Modified: | 16 Dec 2024 01:38 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/89026 |
| DOI: | 10.1002/14651858.CD013877.pub3 |
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