Antimicrobial mouthwashes (gargling) and nasal sprays administered to patients with suspected or confirmed COVID‐19 infection to improve patient outcomes and to protect healthcare workers treating them (Review)

M.J. Burton, Janet E. Clarkson, Beatriz Goulao, Anne-Marie Glenny, Andrew J. McBain, Anne G.M. Schilder, Katie E. Webster, Helen V Worthington

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Abstract

Background
COVID‐19 infection poses a serious risk to patients and – due to its contagious nature – to those healthcare workers (HCWs) treating them. If the mouth and nose of patients with infection are irrigated with antimicrobial solutions, this may help the patients by killing any coronavirus present at those sites. It may also reduce the risk of the active infection being passed to HCWs through droplet transmission or direct contact. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves or alterations in the natural microbial flora of the mouth or nose.

Objectives
To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays administered to patients with suspected or confirmed COVID‐19 infection to both the patients and the HCWs caring for them.

Search methods
Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020.

Selection criteria
This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed RCTs. We therefore planned to include the following types of studies: randomised controlled trials (RCTs); quasi‐RCTs; non‐randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross‐sectional studies; controlled before‐and‐after studies. We set no minimum duration for the studies.

We sought studies comparing antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered with any frequency or dosage to suspected/confirmed COVID‐19 patients.

Data collection and analysis
We used standard Cochrane methodological procedures. Our primary outcomes were: 1) RECOVERY* (www.recoverytrial.net) outcomes in patients (mortality; hospitalisation status; use of ventilation; use of renal dialysis or haemofiltration); 2) incidence of symptomatic or test‐positive COVID‐19 infection in HCWs; 3) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 4) change in COVID‐19 viral load in patients; 5) COVID‐19 viral content of aerosol (when present); 6) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro‐ or nasopharynx; 7) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long‐term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome.

Main results
We found no completed studies to include in this review. We identified 16 ongoing studies (including 14 RCTs), which aim to enrol nearly 1250 participants. The interventions included in these trials are ArtemiC (artemisinin, curcumin, frankincense and vitamin C), Citrox (a bioflavonoid), cetylpyridinium chloride, chlorhexidine, chlorine dioxide, essential oils, hydrogen peroxide, hypertonic saline, Kerecis spray (omega 3 viruxide – containing neem oil and St John's wort), neem extract, nitric oxide releasing solution, povidone iodine and saline with baby shampoo.

Authors' conclusions
We identified no studies for inclusion in this review. This is not surprising given the relatively recent emergence of COVID‐19 infection. It is promising that the question posed in this review is being addressed by a number of RCTs and other studies. We are concerned that few of the ongoing studies specifically state that they will evaluate adverse events such as changes in the sense of smell or to the oral and nasal microbiota, and any consequences thereof.

Very few interventions have large and dramatic effect sizes. If a positive treatment effect is demonstrated when studies are available for inclusion in this review, it may not be large. In these circumstances in particular it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.
Original languageEnglish
Article numberCD013627
Number of pages42
JournalCochrane Database of Systematic Reviews
Volume2020
Issue number9
DOIs
Publication statusPublished - 16 Sept 2020

Bibliographical note

A C K N O W L E D G E M E N T S:
We would like to thank the peer reviewers, Professor Jeremy Bagg, Dr Karolin Hijazi, Professor Carl Philpott and Professor Claire Hopkins, fortheirinsightful comments, which helped us to improve these reviews. Thanks also to Professor Peter Tugwell, Senior Editor Cochrane MOSS Network, for acting as sign-oF editor for these projects. We are also grateful to Doug Salzwedel from the Cochrane Hypertension Group for providing search peer review comments for
the draK search strategy. Professor Schilder's time for this project was supported by the National Institute for Health Research, University College London
Hospitals Biomedical Research Centre, London, UK. This project was supported by the National Institute for Health Research, via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to Cochrane ENT and Cochrane Oral Health. The views and opinions expressed therein are those of
the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Keywords

  • CORONAVIRUS

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