Vaira 2020.

Study characteristics
Methods	Multicentre randomised controlled trial with 40 days of follow‐up
Participants	Location: multicentre, Italy, Belgium, UK Setting of recruitment and treatment: University Hospital of Sassari and the Bellaria‐Maggiore Hospital in Bologna (Italy) Sample size: 18 Number randomised: 9 to intervention, 9 to comparison Number completed: 9 to intervention, 9 to comparison Participants: Participants with COVID‐19 related anosmia for more than 30 days defined as a Connecticut Chemosensory Clinical Research Center (CCCRC) test score ≤ 40 Baseline characteristics: Age: intervention group: median 44.5 years (IQR: 36 to 50.5); control group: median 42 years (IQR: 34 to 48) Gender: intervention group: 4 (44.44%) male and 5 (55.56%) female; control group: 3 (33.33%) male and 6 (66.67%) female Olfactory function at baseline Measured using CCCRC scores Normal (score 90 to 100) Mild hyposmia (70 to 80) Moderate (50 to 60) Severe (20 to 40) Anosmia (0 to 10) Intervention group: median 10 (IQR 15); control group: median 20 (IQR 30) Inclusion criteria for the study: > 18 years of age SARS‐CoV‐2 infection confirmed Recovery from SARS‐CoV‐2 infection confirmed by at least 2 negative swabs CCCRC test score ≤ 40 (i.e. anosmia or severe hyposmia) at 30 days after clinical onset Exclusion criteria for the study: Previous olfactory dysfunction Trauma Nasal surgery Radiation therapy in the oral or nasal cavities Self‐reported allergic rhinitis or rhinosinusitis Psychiatric or neurological disease Contraindication to corticosteroid
Interventions	Intervention group: systemic cortisone therapy with prednisone starting with 1 mg/kg and tapering the dose for 15 days accompanied by nasal irrigation with betamethasone, ambroxol and rinazine for 15 days Comparator group: the control group did not receive any therapy Use of additional interventions: none noted
Outcomes	Outcomes of interest in the review: Primary outcomes: Presence of normal olfactory function Using psychophysical testing (CCCRC) The CCCRC includes a butanol threshold assessment and odour identification test. These scores are converted into CCCRC composite scores, which allows classification of patients Normosmia (recovery) defined as a CCCRC score of 90 to 100 Assessed at baseline, 20 and 40 days Serious adverse effects None noted Change in sense of smell Using psychophysical testing (CCCRC) The CCCRC includes a butanol threshold assessment and odour identification test. These scores are converted into CCCRC composite scores, which allows classification of patients Assessed at baseline, 20 and 40 days Secondary outcomes: Prevalence of parosmia Not assessed Change in sense of taste Not assessed Disease‐related quality of life Not assessed Other adverse effects (including nosebleeds/bloody discharge) None noted Other outcomes reported by the study: None reported
Funding sources	None reported
Declarations of interest	No conflicts of interest declared
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The patients included in the study were randomly divided into two groups using a computer generated random number table" Comment: author contacted and confirmed randomisation
Allocation concealment (selection bias)	Unclear risk	No information provided Comment: author contacted; remains unclear
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Study was not blinded to participants. No placebo was used for the comparator group." Comment: the control group did not undergo any placebo treatment
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Both the researcher who performed the pre‐ and post‐treatment psychophysical assessment of smell and the statistician who analyzed the data were blinded to the patient allocation group" Comment: appropriate blinding performed
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: all 18 patients enrolled were followed up and outcomes reported
Selective reporting (reporting bias)	Unclear risk	Comment: no trial protocol or registration could be identified to assess this
Other bias	Low risk	Comment: no additional sources of bias detected

CCCRC: Connecticut Chemosensory Clinical Research Center
IQR: interquartile range