| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: "Participants were randomized (1:1) using a computer-generated random-number list".
Quote: "Random allocation was done remotely by a member of the study team not involved in participants' enrollment." Comment: Baseline characteristics between intervention groups were comparable; any differences appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Comment: Unblinded study.
No participant cross-over. No information on review co-interventions of interest: antivirals, corticosteroids and biologics. Outcome data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
Low |
Quote: "Additionally, 60 (8.0%) participants were finally excluded from ITT analysis because of negative RT-PCR at baseline, missing RT-PCR at all follow-up visits, or consent withdrawal, yielding an ITT population of 293 Covid-19 patients" Comment: 353 randomized, 293 analyzed. Data was unavailable for more than 5% of those randomized. However, all missing data occurred due to documented reasons unrelated to the outcome. Risk assessed to be low for outcomes: Mortality. WHO score 7 and above. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Unblinded study.
Mortality is an observer-reported outcome not involving judgement. WHO score 7 and above is an outcome that reflects decisions made by the intervention provider. However, we consider that the assessment of these outcomes cannot possibly be influenced by knowledge of the intervention assignment. Risk assessed to be low for outcomes: Mortality. WHO score 7 and above. Adverse events and serious adverse events may contain both clinically- and laboratory-detected outcomes, therefore it can be influenced by knowledge of the intervention assignment, but is not likely to. Risk assessed to be some concerns for outcomes: Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were not available. The registry was available and utilized.
Mortality was not pre-specified in the registry but we consider this acceptable for this outcome as mortality should be reported even if not planned. Result was not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for outcome: Mortality. None of the other outcomes were pre-specified in the registry. No information on whether the results were selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |