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: “Patients were randomized within 72 hours of hospitalization” [article] “Perform subject randomization (via EDC)” [Electronic data capture - Protocol]
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Some concerns |
Quote:"Open-label"
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: Biologics and corticosteroids. Antivirals were the intervention. Hence, no information on whether deviations arose because of the trial context. 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 some concerns for the outcomes: Mortality (D28). Mortality (D60 or more). Viral negative conversion. Time to viral negative conversion. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 50 participants randomized; 50 participants analyzed for efficacy outcomes, 49 participants analyzed for safety outcomes.
Of note, 6 vs 8 participants were loss to follow-up. Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome as the numbers were balanced. Risk assessed to be some concerns for the outcomes: Mortality (D28). Mortality (D60 or more). Time to viral negative conversion. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY. (TIME TO) VIRAL NEGATIVE CONVERSION Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Viral negative conversion. Time to viral negative conversion. WHO SCORE 7 AND ABOVE For this outcome, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: WHO score 7 and above (D28). WHO score 7 and above (D60 or more). CLINICAL IMPROVEMENT Clinical improvement (defined as discharge) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). Clinical improvement (D60 or more). ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan (dated July 15, 2020) and registry consulted up to version dated April 24, 2020 were available.
MORTALITY. WHO SCORE 7 AND ABOVE. CLINICAL IMPROVEMENT. 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 outcomes: Mortality (D28). Mortality (D60). Clinical improvement (D28). Clinical improvement (D60 or more). WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. TIME TO VIRAL NEGATIVE CONVERSION. TIME TO CLINICAL IMPROVEMENT. 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. Time to clinical improvement. |
| Overall risk of bias |
Some concerns |