Rashid 2021.

Study characteristics
Methods	Two‐arm, double‐blind, 2‐centre, parallel‐group RCT with 1 month duration of treatment and follow‐up
Participants	Location: Iraq, 2‐centre study Setting of recruitment and treatment: recruited from 2 ENT outpatients clinics in Iraq (Al Ramadi Teaching Hospital and Tikrit Hospital) Sample size: 276 Number randomised: 138 to intervention, 138 to comparator Number completed: 124 in intervention, 125 in comparator Participants: Adult participants with mild to moderate COVID‐19 and recent onset of anosmia Baseline characteristics: Age: intervention group: median 29 years (IQR 23 to 35), placebo group: median 30 years (IQR 24 to 38) Gender: intervention group: 42 (30.4%) male, 96 (69.6%) female; placebo arm: 36 (26.1%) male, 102 (73.9%) female Olfactory function at baseline: not reported  Diagnosis of olfactory dysfunction at baseline: self‐reported Duration of symptoms: all participants had olfactory disturbance for ≤ 15 days Inclusion criteria: Adults, aged 18 years or over Proven case of COVID‐19 by real‐time PCR of nasopharyngeal/oropharyngeal swabs Recent onset of anosmia, with or without ageusia and other symptoms of COVID‐19 Exclusion criteria: Pregnant women Psychological disturbances Anosmia > 15 days Severe sinonasal disease Previous sinonasal surgery Refusal to participate Lost to follow‐up
Interventions	Intervention group:  Intranasal betamethasone sodium phosphate drops (0.1 mg/mL); 3 drops to each nasal cavity, 3 times daily until recovery, for a maximum of 1 month Comparator group:  Saline placebo 0.9% sodium chloride solution, 3 drops to each nostril 3 times daily until recovery, or for a maximum of 1 month Use of additional interventions in both groups: none reported
Outcomes	Outcomes of interest in the review: Primary outcomes: Presence of normal olfactory function Proportion of participants who had recovered during the follow‐up period (30 days). Self‐reported "recovery" reported during follow‐up phone call. No details on how this was assessed by patients. Also reports median time to recovery of anosmia. Serious adverse effects  Assessed by phone, not reported Change in sense of smell Not reported Secondary outcomes: Prevalence of parosmia Not reported Change in sense of taste Not reported Disease‐related quality of life Not reported Other adverse effects (including nosebleeds/bloody discharge) Assessed by phone, not reported Other outcomes reported by the study: Time to recovery of anosmia was assessed by phone call every 5 days and was self reported by patients
Funding sources	Quote: "This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors."
Declarations of interest	None declared
Notes	Articles states that all participants were analysed, but no information on how this was, given loss to follow‐up (i.e. no description of imputation etc.). Outcome data calculated on the presumption that results are calculated only from those who continued with follow‐up.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomly allocated in 1:1 ratio". Comment: no further details provided.
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided. Note equal numbers randomised to each group, but no report of blocked randomisation. This may suggest that alternate allocation was used (in which case, high risk of bias).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Betamethasone drops were prepared by transferring a pharmaceutically available formulation (Ophatamesone® sterile drops for eye, ear, and nose; Dar Al Dawa, Na’ur, Jordan) into a plain container at aseptic conditions. At similar conditions, 0.9% NaCl intravenous solution was used to prepare placebo drops. Drops were prepared by a pharmacist who was not involved in the study. Treatment arms were concealed to patients and investigators."  Comment: identical packaging appears to have been used. Preparation of intervention/comparator conducted by a separate individual.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Betamethasone drops were prepared by transferring a pharmaceutically available formulation (Ophatamesone® sterile drops for eye, ear, and nose; Dar Al Dawa, Na’ur, Jordan) into a plain container at aseptic conditions. At similar conditions, 0.9% NaCl intravenous solution was used to prepare placebo drops. Drops were prepared by a pharmacist who was not involved in the study. Treatment arms were concealed to patients and investigators."  Comment: subjective outcomes, reported by (blinded) participants.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: loss to follow‐up approximately 10%, and balanced between the groups.
Selective reporting (reporting bias)	Unclear risk	Comment: trial registered retrospectively, after patient recruitment was completed (30 September 2020). Primary outcome reported according to registry data.
Other bias	Unclear risk	Comment: insufficient detail is provided on the conduct of the study to determine whether there may be additional issues resulting in bias. Authors state that outcomes were analysed on an intention‐to‐treat basis for all randomly assigned participants, but no information provided regarding how missing data were accounted for in analyses.