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: “Participants were stratified by age and SARS-CoV-2 local diagnostic results, when available. Participants were randomized according to a central randomization scheme provided by an interactive web response system. A permuted block randomization
scheme with a fixed block length of 2 was used.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: “double-blind”
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 outcome: Hospitalization or death. Mortality (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 314 participants randomized; 311 participants analyzed for mortality, adverse events and serious adverse events; 204 participants analyzed for hospitalization or death.
MORTALITY, ADVERSE and SERIOUS ADVERSE EVENTS Data available for nearly all participants randomized. Risk assessed to be low for the outcome: Mortality (D28). Adverse events. Serious adverse events. HOSPITALIZATION OR DEATH Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: results available for seronegative proportion only Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (similar reasons and proportion of missingness between arms). Risk assessed to be some concerns for the outcome: Hospitalization or death. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcome: Hospitalization or death. Mortality (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The registry was available (prospective, dated June 30 2020). The protocol was also available (dated June 16 2020).
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. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Mortality (D28). HOSPITALIZATION OR DEATH, ADVERSE EVENTS, SERIOUS ADVERSE EVENTS Outcomes pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Hospitalization or death. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |