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 [publication]: “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”
Quote [contact from authors]: "Allocation of participants was concealed to all investigators enrolling new candidate patients through a central randomisation generated list, which was accessed remotely by phone." Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
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: Crossovers: Two patients allocated to CP did not receive any intervention and other 2 patients did not receive the second plasma infusion. One participant in the control group received a single transfusion of CP. No information on administration of co-interventions of interest: antivirals and biologics. Corticosteroids were reported and balanced between groups. 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. MORTALITY, TIME TO DEATH, (TIME TO) CLINICAL IMPROVEMENT, (TIME TO) WHO SCORE 7 AND ABOVE, AE, SAE Our analysis for the binary outcome is an 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). Time to WHO score 7 and above. Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 21 vs 22 participants were excluded from the analysis post-randomization because for unclear reasons likely due to missing data which is accounted for in domain 3. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| Missing outcome data |
Some concerns |
Comment: 160 participants randomized; 160 participants analyzed for most outcomes; 117 analyzed for negative conversion.
MORTALITY, TIME TO DEATH, (TIME TO) CLINICAL IMPROVEMENT, (TIME TO) WHO SCORE 7 AND ABOVE, AE, SAE Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Time to WHO score 7 and above. WHO score 7 and above (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: Unclear Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (missingness balanced between arms). Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| 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, 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). Time to WHO score 7 and above. CLINICAL IMPROVEMENT 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 |
Low |
Comment: The prospective protocol, statistical analysis plan and retrospective registry were available.
MORTALITY, VIRAL NEGATIVE CONVERSION, WHO SCORE 7 AND ABOVE, AE, SAE 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). WHO score 7 and above (D28). Adverse events. Serious adverse events. CLINICAL IMPROVEMENT, TIME TO WHO SCORE 7 AND ABOVE Outcome data acquired from contact with authors. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Clinical improvement (D28). Time to WHO score 7 and above. |
| Overall risk of bias |
Some concerns |