Ask the Experts: An International Consensus on Managing Post-Infectious Olfactory Dysfunction Including COVID-19.

Purpose of Review: To summarise the current understanding of post-infectious olfactory dysfunction (PIOD) and provide a consensus on management of the condition through an evidence-based approach, critically reviewing the available management options. Recent Findings: New studies investigating the pathophysiology of PIOD in COVID-19 patients have found that in those with persistent symptoms there is an association with lower tissue perfusion in the orbital and medial regions of the frontal lobe. Recent meta-analyses have listed olfactory training as the first line management for PIOD. Summary: Olfactory training remains the most recommended management option for PIOD. The use of systemic corticosteroids to treat PIOD is not encouraged due to poor evidence.

Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.

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Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials.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.

Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is a common consequence of COVID-19 infection and persistent symptoms can have a profound impact on quality of life. At present there is little guidance on how best to treat this condition. A variety of interventions have been suggested to promote recovery, including medication and olfactory training. However, it is uncertain whether any intervention is of benefit. This is an update of the 2021 review with one additional study added.  OBJECTIVES: 1) To evaluate the benefits and harms of any intervention versus no treatment for people with persisting 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 that had persisted for at least 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 recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia 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 two studies with 30 participants. The studies evaluated the following interventions: systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant and palmitoylethanolamide plus luteolin.  Systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant compared to no intervention We included a single RCT with 18 participants who had anosmia for at least 30 days following COVID-19 infection. Participants received a 15-day course of oral corticosteroids combined with nasal irrigation (consisting of an intranasal corticosteroid/mucolytic/decongestant solution) or no intervention. Psychophysical testing was used to assess olfactory function at 40 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results. Palmitoylethanolamide plus luteolin compared to no intervention We included a single RCT with 12 participants who had anosmia or hyposmia for at least 90 days following COVID-19 infection. Participants received a 30-day course of palmitoylethanolamide and luteolin or no intervention. Psychophysical testing was used to assess olfactory function at 30 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results. AUTHORS' CONCLUSIONS: There is very limited evidence available on the efficacy and harms of treatments for 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.

Interventions for the prevention of persistent post‐COVID‐19 olfactory dysfunction

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID‐19 infection. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach.

Effects of fluid and drinking on pneumonia mortality in older adults: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Advice to drink plenty of fluid is common in respiratory infections. We assessed whether low fluid intake (dehydration) altered outcomes in adults with pneumonia. METHODS: We systematically reviewed trials increasing fluid intake and well-adjusted, well-powered observational studies assessing associations between markers of low-intake dehydration (fluid intake, serum osmolality, urea or blood urea nitrogen, urinary output, signs of dehydration) and mortality in adult pneumonia patients (with any type of pneumonia, including community acquired, health-care acquired, aspiration, COVID-19 and mixed types). Medline, Embase, CENTRAL, references of reviews and included studies were searched to 30/10/2020. Studies were assessed for inclusion, risk of bias and data extracted independently in duplicate. We employed random-effects meta-analysis, sensitivity analyses, subgrouping and GRADE assessment. Prospero registration: CRD42020182599. RESULTS: We identified one trial, 20 well-adjusted cohort studies and one case-control study. None suggested that more fluid (hydration) was associated with harm. Ten of 13 well-powered observational studies found statistically significant positive associations in adjusted analyses between dehydration and medium-term mortality. The other three studies found no significant effect. Meta-analysis suggested doubled odds of medium-term mortality in dehydrated (compared to hydrated) pneumonia patients (GRADE moderate-quality evidence, OR 2.3, 95% CI 1.8 to 2.8, 8619 deaths in 128,319 participants). Heterogeneity was explained by a dose effect (greater dehydration increased risk of mortality further), and the effect was consistent across types of pneumonia (including community-acquired, hospital-acquired, aspiration, nursing and health-care associated, and mixed pneumonia), age and setting (community or hospital). The single trial found that educating pneumonia patients to drink ≥1.5 L fluid/d alongside lifestyle advice increased fluid intake and reduced subsequent healthcare use. No studies in COVID-19 pneumonia met the inclusion criteria, but 70% of those hospitalised with COVID-19 have pneumonia. Smaller COVID-19 studies suggested that hydration is as important in COVID-19 pneumonia mortality as in other pneumonias. CONCLUSIONS: We found consistent moderate-quality evidence mainly from observational studies that improving hydration reduces the risk of medium-term mortality in all types of pneumonia. It is remarkable that while many studies included dehydration as a potential confounder, and major pneumonia risk scores include measures of hydration, optimal fluid volume and the effect of supporting hydration have not been assessed in randomised controlled trials of people with pneumonia. Such trials, are needed as potential benefits may be large, rapid and implemented at low cost. Supporting hydration and reversing dehydration has the potential to have rapid positive impacts on pneumonia outcomes, and perhaps also COVID-19 pneumonia outcomes, in older adults.

Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.

BACKGROUND: Loss of olfactory function is well recognised as a cardinal symptom of COVID-19 infection, and the ongoing pandemic has resulted in a large number of affected 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.  OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Individuals who had symptoms for less than four weeks were included in this review. Studies compared any intervention with no treatment or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. 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 one study of 100 participants, which compared an intranasal steroid spray to no intervention. Participants in both groups were also advised to undertake olfactory training for the duration of the trial. Data were identified for only two of the prespecified outcomes for this review, and no data were available for the primary outcome of serious adverse effects. Intranasal corticosteroids compared to no intervention (all using olfactory training) Presence of normal olfactory function after three weeks of treatment was self-assessed by the participants, using a visual analogue scale (range 0 to 10, higher scores = better). A score of 10 represented "completely normal smell sensation". The evidence is very uncertain about the effect of intranasal corticosteroids on self-rated recovery of sense of smell (estimated absolute effect 619 per 1000 compared to 520 per 1000, risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; very low-certainty evidence).  Change in sense of smell was not reported, but the self-rated score for sense of smell was reported at the endpoint of the study with the same visual analogue scale (after three weeks of treatment). The median scores at endpoint were 10 (interquartile range (IQR) 9 to 10) for the group receiving intranasal corticosteroids, and 10 (IQR 5 to 10) for the group receiving no intervention (1 study; 100 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following COVID-19 infection. However, we have identified a small number of additional ongoing studies in this area. As this is a living systematic review, the evidence will be updated regularly to incorporate new data from these, and other relevant studies, as they become available.  For this (first) version of the living review, we identified a single study of intranasal corticosteroids to include in this review, which provided data for only two of our prespecified outcomes. The evidence was of very low certainty, therefore we were unable to determine whether intranasal corticosteroids may have a beneficial or harmful effect.

Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can have a profound effect on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction, however several strategies have been proposed from the evidence relating to the treatment of post-viral anosmia (such as medication or olfactory training). OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to treat persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Only individuals who had symptoms for at least four weeks were included in this review. Studies compared any intervention with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia 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 one study with 18 participants, which compared the use of a 15-day course of oral steroids combined with nasal irrigation (consisting of an intranasal steroid/mucolytic/decongestant solution) with no intervention. Psychophysical testing was used to assess olfactory function at baseline, 20 and 40 days. Systemic corticosteroids plus intranasal steroid/mucolytic/decongestant compared to no intervention Recovery of sense of smell was assessed after 40 days (25 days after cessation of treatment) using the Connecticut Chemosensory Clinical Research Center (CCCRC) score. This tool has a range of 0 to 100, and a score of ≥ 90 represents normal olfactory function. The evidence is very uncertain about the effect of this intervention on recovery of the sense of smell at one to three months (5/9 participants in the intervention group scored ≥ 90 compared to 0/9 in the control group; risk ratio (RR) 11.00, 95% confidence interval (CI) 0.70 to 173.66; 1 study; 18 participants; very low-certainty evidence). Change in sense of smell was assessed using the CCCRC score at 40 days. This study reported an improvement in sense of smell in the intervention group from baseline (median improvement in CCCRC score 60, interquartile range (IQR) 40) compared to the control group (median improvement in CCCRC score 30, IQR 25) (1 study; 18 participants; very low-certainty evidence). Serious adverse events andother adverse events were not identified in any participants of this study; however, it is unclear how these outcomes were assessed and recorded (1 study; 18 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified other ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available. For this (first) version of the living review we identified only one study with a small sample size, which assessed systemic steroids and nasal irrigation (intranasal steroid/mucolytic/decongestant). However, the evidence regarding the benefits and harms from this intervention to treat persistent post-COVID-19 olfactory dysfunction is very uncertain.

Systemic corticosteroids in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view.

The frequent association between coronavirus disease 2019 (COVID-19) and olfactory dysfunction is creating an unprecedented demand for a treatment of the olfactory loss. Systemic corticosteroids have been considered as a therapeutic option. However, based on current literature, we call for caution using these treatments in early COVID-19-related olfactory dysfunction because: (1) evidence supporting their usefulness is weak; (2) the rate of spontaneous recovery of COVID-19-related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. We encourage randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize to initially consider smell training, which is supported by a robust evidence base and has no known side effects.

Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction.

BACKGROUND: Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD). OBJECTIVE: Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists. METHODS: A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD. RESULTS: The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction. CONCLUSIONS: The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options.

Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms.

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

Management of new onset loss of sense of smell during the COVID-19 pandemic - BRS Consensus Guidelines.

OBJECTIVES: The primary aim of the study is to provide recommendations for the investigation and management of patients with new onset loss of sense of smell during the COVID-19 pandemic. DESIGN: After undertaking a literature review, we used the RAND/UCLA methodology with a multi-step process to reach consensus about treatment options, onward referral, and imaging. SETTING AND PARTICIPANTS: An expert panel consisting of 15 members was assembled. A literature review was undertaken prior to the study and evidence was summarised for the panellists. MAIN OUTCOME MEASURES: The panel undertook a process of ranking and classifying appropriateness of different investigations and treatment options for new onset loss of sense of smell during the COVID-19 pandemic. Using a 9-point Likert scale, panellists scored whether a treatment was: Not recommended, optional, or recommended. Consensus was achieved when more than 70% of responses fell into the category defined by the mean. RESULTS: Consensus was reached on the majority of statements after 2 rounds of ranking. Disagreement meant no recommendation was made regarding one treatment, using Vitamin A drops. Alpha-lipoic acid was not recommended, olfactory training was recommended for all patients with persistent loss of sense of smell of more than 2 weeks duration, and oral steroids, steroid rinses, and omega 3 supplements may be considered on an individual basis. Recommendations regarding the need for referral and investigation have been made. CONCLUSION: This study identified the appropriateness of olfactory training, different medical treatment options, referral guidelines and imaging for patients with COVID-19-related loss of sense of smell. The guideline may evolve as our experience of COVID-19 develops.

Is loss of sense of smell a diagnostic marker in COVID-19: A systematic review and meta-analysis.

AIMS: To systematically review the currently available evidence investigating the association between olfactory dysfunction (OD) and the novel coronavirus (COVID-19). To analyse the prevalence of OD in patients who have tested positive on polymerase chain reaction (PCR) for COVID-19. To perform a meta-analysis of patients presenting with olfactory dysfunction, during the pandemic, and to investigate the positive predictive value for a COVID-19-positive result in this population. To assess whether olfactory dysfunction could be used as a diagnostic marker for COVID-19 positivity and aid public health approaches in tackling the current outbreak. METHODS: We systematically searched MedLine (PubMed), Embase, Health Management Information Consortium (HMIC), Medrxiv, the Cochrane Library, the Cochrane COVID-19 Study Register, NIHR Dissemination centre, Clinical Evidence, National Health Service Evidence and the National Institute of Clinical Excellence to identify the current published evidence which associates coronaviridae or similar RNA viruses with anosmia. The initial search identified 157 articles. A total of 145 papers were excluded following application of our exclusion criteria. The 12 remaining articles that presented evidence on the association between COVID-19 and olfactory dysfunction were critically analysed. RESULTS: Olfactory dysfunction has been shown to be the strongest predictor of COVID-19 positivity when compared to other symptoms in logistic regression analysis. In patients who had tested positive for COVID-19, there was a prevalence of 62% of OD. In populations of patients who are currently reporting OD, there is a positive predictive value of 61% for a positive COVID-19 result. CONCLUSION: Our review has shown that there is already significant evidence which demonstrates an association between OD and the novel coronavirus-COVID-19. It is unclear if this finding is unique to this coronavirus as individual viral phenotypes rarely present in such concentrated large numbers. We have demonstrated that OD is comparatively more predictive for COVID-19 positivity compared to other associated symptoms. We recommend that people who develop OD during the pandemic should be self-isolate and this guidance should be adopted internationally to prevent transmission.