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 of patients was performed through an interactive response technology system using time from the onset of COVID-19 to randomization (<72 hours/≥72 hours) and the first COVID-19 vaccination (Yes/No) as stratification factors.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Investigators, patients, and other study staff remained blinded until the completion of the 28-day follow-up period.”
Comment: Blinded study (participants and personnel/carers) Our analysis for the outcomes 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: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 428 participants randomized; 421 participants analyzed for safety outcomes; 332 participants analyzed for viral negative conversion;
HOSPITALIZATION OR DEATH. MORTALITY. ADVERSE EVENTS. SERIOUS ADVERSE EVENTS. Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. (TIME TO) VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: negative tests at baseline Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). Time to viral negative conversion. |
| 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 outcomes: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The prospective registry was available (dated September 28th, 2021).
VIRAL NEGATIVE CONVERSION Outcome 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 outcomes: Hospitalization or death. Incidence of viral negative conversion (D7). Time to viral negative conversion. 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 AND SERIOUS ADVERSE EVENTS Safety outcomes not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified for safety outcomes. Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events. TIME TO VIRAL NEGATIVE CONVERSION. WHO SCORE 7 AND ABOVE. Outcome data acquired from direct contact with authors. Analysis performed by the COVID-NMA. Risk assessed to be low for the outcome: Time to viral negative conversion. WHO score 7 and above (D28). |
| Overall risk of bias |
Some concerns |