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|
|Quote: "Eligible participants were randomly assigned in 4:1 ratio (40 tests: 10 controls) by sequentially numbered opaque sealed envelope simple randomization method, either to receive C-IVIG plus SOC (intervention group), or only SOC (control group). A randomization list was generated by a hospital personnel unrelated to this study while the study personnel were unaware of the sequence of assignment. At the time of randomization, the study personnel received a sealed opaque envelope with assignment to intervention or control group."
Comment: Allocation sequence random. Allocation sequence concealed.
|Deviations from intervention||
|Quote: "single-blinded trial" "All participants were blinded"
Comment: Unclear blinding (participants described as blinded but no placebo used).
Deviations from intended intervention arising because of the study context:
No participant cross-over.
Administration of co-interventions of interest: antivirals and corticosteroids were reported and were balanced between groups. Biologics administered to 2/10 in the control group but to only 1/40 in the intervention group.
This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect.
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). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events.
|Missing outcome data||
|Comment: 50 participants randomized; 49 participants analyzed.
Data available for nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events.
|Measurement of the outcome||
|Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Unblinded study (outcome assessor).
Mortality is an observer-reported outcome not involving judgement.
Risk assessed to be low for the outcome: Mortality (D28).
WHO SCORE 7 AND ABOVE
For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment.
Risk assessed to be low for the outcome: WHO score 7 and above (D28).
Clinical improvement (defined as hospital 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 outcome: Clinical improvement (D28).
The authors reported on 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 outcome: Adverse events.
|Selection of the reported results||
|Comment: The protocol and registry (August 20 2020) were available. The registration was made 2 months after start of recruitment, but nearly 6 months before study end, with no subsequent changes in outcomes.
Mortality and adverse events outcomes were pre-specified.
These results were not selected from multiple outcome measurements or analyses of the data.
These outcomes were analyzed as pre-specified.
Risk assessed to be low for the outcome: Mortality (D28). Adverse events.
The ordinal scale on which clinical improvement (hospital discharge) and WHO score 7 or above outcome data are based was not included in the registry or protocol.
Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). WHO score 7 and above (D28).
|Overall risk of bias||