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: “Randomisation was performed using computer-generated randomisation with random block sizes of 2 or 4 and stratified according to the unit of hospitalisation on enrolment”
Comment: Allocation sequence random. No information on allocation concealment.
|Deviations from intervention||
|Quote: “Open-label. Patients and investigators were unmasked, except interviewers performing follow-up telephone calls, who was unaware of the assigned trial group.”
Comment: Unblinded study (participants and personnel/carers)
Deviations from intended intervention arising because of the study context:
1 participant in the standard care arm was excluded from analysis because they received convalescent plasma.
5 participants in the convalescent plasma arm were excluded from analysis: 2 because they received none (1 none available, 1 died before administration) and 3 because the did not receive 2 doses per protocol (2 received on dose, 1 received 4 extra doses).
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.
Crossovers: For safety, 1 participant in the standard of care arm who receive plasma was analyzed in the plasma arm, and 2 in the plasma arm who received none were analyzed in the standard of care arm.
No information on administration of co-interventions of interest: antivirals and biologics. Corticosteroids were reported and balanced between groups.
Hence, no 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). Time to death. Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.
|Missing outcome data||
|Comment: 160 participants randomized; 154 participants analyzed for most outcomes; 117 analyzed for negative conversion.
Data available for nearly all participants randomized for most outcomes.
Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.
Data not available for all or nearly all participants for negative conversion, 27% missing data.
No evidence that the result is not biased.
Reasons: Unclear why data missing for some patients, but balanced between groups.
Not likely that missingness depended on the true value of the outcome.
Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7).
|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, TIME TO DEATH, VIRAL NEGATIVE CONVERSION
Mortality and viral negative conversion are observer-reported outcomes not involving judgement.
Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Incidence of viral negative conversion (D7).
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 outcomes: WHO score 7 and above (D28).
Clinical improvement (defined as hospital discharge or an improvement of 2 points on a 6-point ordinal scale) 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).
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||
|Comment: The prospective protocol, statistical analysis plan and retrospective registry were available.
Outcomes pre-specified in protocol.
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). Time to death. Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events.
|Overall risk of bias||