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 stratified by the center and oxygen therapy (nasal cannula or mask, or high-flow oxygen, noninvasive ventilation). A statistician who was masked to trial allocation generated the permuted block (4 patients per block) randomization sequence by using SAS software (version 9.4; SAS Institute). Randomization was conducted by using the Interactive Voice Response service provided by Guangzhou University. The allocation team was masked to the block size and random allocation table."
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Comment: Unblinded study (participants and personnel/carers).
Deviations from intended intervention arising because of the study context: Two participants who were allocated to the intervention group did not receive the intervention. Co-intervention administration of corticosteroids and antivirals are reported. No information on biologics. Hence, not enough information on whether deviations arose because of the trial context. Data for the outcome were analyzed using 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). Time to death. Time to clinical improvement. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 200 participants randomized; 200 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Time to clinical improvement. 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 DEATH Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. TIME TO CLINICAL IMPROVEMENT Clinical improvement (defined as at least one point improvement on a seven point scale or 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: Time to clinical improvement. 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 |
Some concerns |
Comment: The protocol (dated February 1st, 2020) and statistical analysis plan were available.
TIME TO DEATH, TIME TO CLINICAL IMPROVEMENT, AE, SAE Outcomes reported as 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: Time to death. Time to clinical improvement. Adverse events. Serious adverse events. MORTALITY Timepoints reported were 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. Risk assessed to be some concerns for the outcome: Mortality (D28). Mortality (D60 or more). |
| Overall risk of bias |
Some concerns |