| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: "Randomization was performed in blocks
of six and was stratified according to the use or
nonuse of supplemental oxygen at the time of
randomization. Randomization was performed
centrally by means of an electronic case-report
form system (RedCap)". Quote from Supplementary Appendix: "The trial statistician, not involved with patient enrolment or care, generated the rndomization table in R software (R Core Team, 2019) and implemented in the RedCap. The study treatment was revealed to investigators only after patients were registered in the RedCap, ensuring proper concealment of the allocation sequence." Comment: Baseline characteristics between intervention groups were comparable; any differences appear to be compatible with chance. |
| Deviations from intervention |
High |
Comment: Unblinded study. A proportion of patients in all three groups received trial drugs in the 24 hours prior to randomization. Co-intervention administration for corticosteroids, antivirals and antibiotics are reported in Table S2 and in balanced per arm proportions. No information on review co-intervention of interest: biologics. Outcome data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
Low |
Comment: 2 patients were also excluded from analysis due to consent withdrawal after randomization (n=1) and duplicated randomization (n=1). Therefore, 667 randomized, 665 analyzed. All missing data occurred due to documented reasons unrelated to the outcome. Risk assessed to be low for outcomes: Mortality. Time to death. Incidence of WHO score 6 and above. Incidence of WHO score 7 and above. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Mortality is an observer-reported outcome not involving judgement. Incidence of 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. Time to death. Incidence of WHO score 7 and above. For Score 6 and above, although the assessment could possibly be influenced by knowledge of the intervention assignment, we did not consider this likely to have happened in the context of a pandemic. 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: Incidence of WHO score 6 and above. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan were available. Risk assessed to be low for the outcomes: Mortality. Time to death. Incidence of WHO score 6 and above. Incidence of WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
High |