Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.
Bias | Author's judgement | Support for judgement |
Randomization |
Low |
Quote: “Randomization was managed centrally by a contracted third-party using electronic interactive randomization technology.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
Deviations from intervention |
Low |
Quote: “Randomization was managed centrally by a contracted third-party using electronic interactive randomization technology. The randomization list was masked to study participants, the sponsor, investigators, study monitors, and laboratory personnel until the database was locked.”
Comment: Blinded study (participants and personnel/carers). Our analysis for the binary outcome is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Mortality (D28). Hospitalization or death. Adverse events. Serious adverse events. |
Missing outcome data |
Some concerns |
Comment: 1092 participants randomized; 935 participants analyzed for all outcomes except hospitalization or death (379 analyzed).
MORTALITY, ADVERSE EVENTS, SERIOUS ADVERSE EVENTS Data not available for all or nearly all of population. Reasons for missing data: 1 participant withdrew consent before treatment. 156 subjects positive for rhinovirus/enterovirus and negative for SARS-CoV-2 at baseline were not included in any analysis as they are to be analyzed later as part of a separate study targeting enterovirus/ rhinovirus infection. Missingness could depend on the true value of the outcome. Unlikely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Mortality (D28). Adverse events. Serious adverse events. HOSPITALIZATION OR DEATH Data not available for all or nearly all of population. Reasons for missing data: 1 participant withdrew consent before treatment. 156 subjects positive for rhinovirus/enterovirus and negative for SARS-CoV-2 at baseline were not included in any analysis as they are to be analyzed later as part of a separate study targeting enterovirus/ rhinovirus infection. 288 vs 268 negative for SARS-COV-2 Missingness could depend on the true value of the outcome. Unlikely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Hospitalization or death. |
Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Hospitalization or death. Adverse events. Serious adverse events. |
Selection of the reported results |
Some concerns |
Comment: The prospective trial registry was available.
MORTALITY Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Risk assessed to be low for the outcome: Mortality (D28). HOSPITALIZATION OR DEATH. ADVERSE and SERIOUS ADVERSE EVENTS Outcomes not prespecified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for outcomes: Hospitalization or death. Adverse events. Serious adverse events. |
Overall risk of bias |
Some concerns |