Martin J Burton1, Janet E Clarkson2, Beatriz Goulao3, Anne-Marie Glenny4, Andrew J McBain5, Anne Gm Schilder6,7, Katie E Webster8, Helen V Worthington9. 1. Cochrane UK, Oxford, UK. 2. Division of Oral Health Sciences, Dundee Dental School, University of Dundee, Dundee, UK. 3. Heath Services Research Unit, University of Aberdeen, Aberdeen, UK. 4. Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. 5. Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. 6. evidENT, Ear Institute, University College London, London, UK. 7. National Institute of Health Research, University College London Hospitals Biomedical Research Centre, London, UK. 8. Cochrane ENT, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. 9. Cochrane Oral Health, Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
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 HCWs are irrigated with antimicrobial solutions, this may help reduce the risk of active infection being passed from infected patients 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. Understanding these possible side effects is particularly important when the HCWs are otherwise fit and well. OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays used by healthcare workers (HCWs) to protect themselves when treating patients with suspected or confirmed COVID-19 infection. 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of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials.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 randomised controlled trials (RCTs). We therefore planned to include the following types of studies: 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 any antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered to HCWs, with or without the same intervention being given to the patients with COVID-19. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 2) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 3) viral content of aerosol, when present (if intervention administered to patients); 4) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 5) 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 three ongoing studies (including two RCTs), which aim to enrol nearly 700 participants. The interventions included in these trials are povidone iodine, nitric oxide and GLS-1200 oral spray (the constituent of this spray is unclear and may not be antimicrobial in nature). 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 two RCTs and a non-randomised study. We are concerned that only one of the ongoing studies specifically states that it will evaluate adverse events and it is not clear if this will include 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, where those receiving the intervention are otherwise fit and well, it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.
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 HCWs are irrigated with antimicrobial solutions, this may help reduce the risk of active infection being passed from infected patients 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. Understanding these possible side effects is particularly important when the HCWs are otherwise fit and well. OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays used by healthcare workers (HCWs) to protect themselves when treating patients with suspected or confirmed COVID-19 infection. 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 randomised controlled trials (RCTs). We therefore planned to include the following types of studies: 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 any antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered to HCWs, with or without the same intervention being given to the patients with COVID-19. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 2) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 3) viral content of aerosol, when present (if intervention administered to patients); 4) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 5) 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 three ongoing studies (including two RCTs), which aim to enrol nearly 700 participants. The interventions included in these trials are povidone iodine, nitric oxide and GLS-1200 oral spray (the constituent of this spray is unclear and may not be antimicrobial in nature). 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 two RCTs and a non-randomised study. We are concerned that only one of the ongoing studies specifically states that it will evaluate adverse events and it is not clear if this will include 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, where those receiving the intervention are otherwise fit and well, it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.
Authors: M Kilian; I L C Chapple; M Hannig; P D Marsh; V Meuric; A M L Pedersen; M S Tonetti; W G Wade; E Zaura Journal: Br Dent J Date: 2016-11-18 Impact factor: 1.626
Authors: Miranda Cumpston; Tianjing Li; Matthew J Page; Jacqueline Chandler; Vivian A Welch; Julian Pt Higgins; James Thomas Journal: Cochrane Database Syst Rev Date: 2019-10-03
Authors: Martin J Burton; Janet E Clarkson; Beatriz Goulao; Anne-Marie Glenny; Andrew J McBain; Anne Gm Schilder; Katie E Webster; Helen V Worthington Journal: Cochrane Database Syst Rev Date: 2020-09-16
Authors: Emma C Goodall; Andrea C Granados; Kathy Luinstra; Eleanor Pullenayegum; Brenda L Coleman; Mark Loeb; Marek Smieja Journal: BMC Infect Dis Date: 2014-05-19 Impact factor: 3.090
Authors: Harman S Parhar; Kendall Tasche; Robert M Brody; Gregory S Weinstein; Bert W O'Malley; Rabie M Shanti; Jason G Newman Journal: Head Neck Date: 2020-04-25 Impact factor: 3.147
Authors: Peter Horby; Wei Shen Lim; Jonathan R Emberson; Marion Mafham; Jennifer L Bell; Louise Linsell; Natalie Staplin; Christopher Brightling; Andrew Ustianowski; Einas Elmahi; Benjamin Prudon; Christopher Green; Timothy Felton; David Chadwick; Kanchan Rege; Christopher Fegan; Lucy C Chappell; Saul N Faust; Thomas Jaki; Katie Jeffery; Alan Montgomery; Kathryn Rowan; Edmund Juszczak; J Kenneth Baillie; Richard Haynes; Martin J Landray Journal: N Engl J Med Date: 2020-07-17 Impact factor: 91.245
Authors: Lyn R Frumkin; Michaela Lucas; Curtis L Scribner; Nastassja Ortega-Heinly; Jayden Rogers; Gang Yin; Trevor J Hallam; Alice Yam; Kristin Bedard; Rebecca Begley; Courtney A Cohen; Catherine V Badger; Shawn A Abbasi; John M Dye; Brian McMillan; Michael Wallach; Traci L Bricker; Astha Joshi; Adrianus C M Boon; Suman Pokhrel; Benjamin R Kraemer; Lucia Lee; Stephen Kargotich; Mahima Agochiya; Tom St John; Daria Mochly-Rosen Journal: Front Immunol Date: 2022-06-01 Impact factor: 8.786
Authors: Ana Beatriz Pizarro; Emma Persad; Solange Durao; Barbara Nussbaumer-Streit; Jean S Engela-Volker; Damien McElvenny; Sarah Rhodes; Katie Stocking; Tony Fletcher; Craig Martin; Kukuh Noertjojo; Olivia Sampson; Jos H Verbeek; Karsten Juhl Jørgensen; Matteo Bruschettini Journal: Cochrane Database Syst Rev Date: 2022-05-06
Authors: Mason Bahador; Rayyan A Alfirdous; Theeb A Alquria; Ina L Griffin; Patricia A Tordik; Frederico C Martinho Journal: J Endod Date: 2021-02-03 Impact factor: 4.171
Authors: Martin J Burton; Janet E Clarkson; Beatriz Goulao; Anne-Marie Glenny; Andrew J McBain; Anne Gm Schilder; Katie E Webster; Helen V Worthington Journal: Cochrane Database Syst Rev Date: 2020-09-16
Authors: Martin J Burton; Janet E Clarkson; Beatriz Goulao; Anne-Marie Glenny; Andrew J McBain; Anne Gm Schilder; Katie E Webster; Helen V Worthington Journal: Cochrane Database Syst Rev Date: 2020-09-16