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Effective early strategy to prevent olfactory and gustatory dysfunction in COVID-19: a randomized controlled trial

Jing et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcad262, ChiCTR2200059651
Nov 2023  
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Olfactory or gustatory dy.. 71% OGD Improvement Relative Risk VAS olfactory severe 97% VAS gustatory severe 95% TSS severe 93% NaCl  Jing et al.  EARLY TREATMENT  DB RCT Is early treatment with NaCl beneficial for COVID-19? Double-blind RCT 260 patients in China (May - June 2022) Lower progression (p<0.0001) and severe cases (p<0.0001) c19early.org Jing et al., QJM: An Int. J. Medicine, Nov 2023 FavorsNaCl Favorscontrol 0 0.5 1 1.5 2+
RCT 379 mild COVID-19 cases showing significantly lower prevalence and severity of olfactory and gustatory dysfunction with budesonide nasal spray, chlorhexidine mouthwash, and saline nasal irrigation. The control group received no intervention, the saline group received saline nasal irrigation plus saline nasal spray and mouthwash, and the drug group received saline nasal irrigation plus budesonide nasal spray and chlorhexidine mouthwash. Saline nasal irrigation plus nasal spray and mouthwash were administered once and four times daily, respectively. Both treatment groups had significantly lower prevalence and severity olfactory and gustatory dysfunction. Prevalence was lower for the drug vs. saline group, without statistical significance.
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects.
Standard of Care (SOC): SOC for COVID-19 in the study country, China, is average with moderate average efficacy for approved treatments1.
Study covers budesonide and chlorhexidine.
olfactory or gustatory dysfunction, 70.8% lower, RR 0.29, p < 0.001, treatment 14 of 120 (11.7%), control 56 of 140 (40.0%), NNT 3.5, OGD.
VAS olfactory severe, 96.5% lower, RR 0.03, p < 0.001, treatment 0 of 120 (0.0%), control 15 of 140 (10.7%), NNT 9.3, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
VAS gustatory severe, 95.3% lower, RR 0.05, p = 0.001, treatment 0 of 120 (0.0%), control 11 of 140 (7.9%), NNT 13, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
TSS severe, 92.9% lower, RR 0.07, p = 0.02, treatment 0 of 120 (0.0%), control 7 of 140 (5.0%), NNT 20, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Jing et al., 21 Nov 2023, Double Blind Randomized Controlled Trial, China, peer-reviewed, 7 authors, study period 5 May, 2022 - 16 June, 2022, trial ChiCTR2200059651. Contact: chengli_2017@tongji.edu.cn.
This PaperNaClAll
DOI record: { "DOI": "10.1093/qjmed/hcad262", "ISSN": [ "1460-2725", "1460-2393" ], "URL": "http://dx.doi.org/10.1093/qjmed/hcad262", "abstract": "<jats:title>Summary</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Olfactory and gustatory dysfunctions (OGDs) are key symptoms of coronavirus disease 2019 (COVID-19), which may lead to neurological complications, and lack of effective treatment. This may be because post-disease treatments may be too late to protect the olfactory and gustatory functions.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Aim</jats:title>\n <jats:p>To evaluate the effectiveness of early use of saline nasal irrigation (SNI), corticosteroid nasal spray, and saline or chlorhexidine gluconate mouthwash for preventing OGDs in COVID-19.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Design</jats:title>\n <jats:p>This study was a double-blind randomized controlled trial.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>The study was conducted from 5 May to 16 June 2022. We recruited patients from three hospitals who were admitted with COVID-19 but without OGDs on the day of admission. Olfactory and gustatory functions were evaluated using the Taste and Smell Survey and the numerical visual analog scale. Participants were randomized to the saline, drug or control groups. The control group received no intervention, saline group received SNI plus saline nasal spray and mouthwash, and the trial group received SNI plus budesonide nasal spray and chlorhexidine gluconate mouthwash. Participants were assessed again on the day of discharge.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>A total of 379 patients completed the trial. The prevalence of OGDs was significantly lower in the saline (11.8%, 95% CI, 6.6–19.0%; P &amp;lt; 0.001) and drug (8.3%, 95% CI, 4.1–14.8%; P &amp;lt; 0.001) groups than in the control group (40.0%, 95% CI, 31.8–48.6%). Additionally, both interventions reduced the severity of OGDs.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>We demonstrated effective strategies for preventing COVID-19-related OGDs, and the findings may guide early management of severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection to reduce the incidence of COVID-19-related complications.</jats:p>\n </jats:sec>", "author": [ { "ORCID": "http://orcid.org/0000-0003-0714-2661", "affiliation": [ { "name": "Department of Anesthesiology and Perioperative Medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University , Shanghai 200434, China" } ], "authenticated-orcid": false, "family": "Jing", "given": "Q", "sequence": "first" }, { "affiliation": [ { "name": "Department of Anesthesiology and Perioperative Medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University , Shanghai 200434, China" } ], "family": "Song", "given": "J", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Anesthesiology and Perioperative Medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University , Shanghai 200434, China" } ], "family": "An", "given": "G", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medical Statistics, Tongji University School of Medicine , Shanghai 200092, China" } ], "family": "Zhu", "given": "E", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Medical Statistics, Tongji University School of Medicine , Shanghai 200092, China" } ], "family": "Ai", "given": "Z", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Anesthesiology and Perioperative Medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University , Shanghai 200434, China" } ], "family": "Xiong", "given": "L", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Anesthesiology and Perioperative Medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative 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