| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: "The enrolled patients were randomly allocated into two groups (1:1 allocation ratio) by an independent statistician using permuted blocks of 4 for all sites. The whole process of randomization was masked to all treating physicians. Patient unique identification number and treatment allocation codes were provided by a clinical research associate in sequentially numbered opaque envelopes." Comment: The allocation sequence was concealed. |
| Deviations from intervention |
Low |
Comment: participants and staff were blinded except for the treating physicians. There was a slight imbalance in the receipt of biologic co-interventions ( 7 vs 11 participants in the treatment and the control arm, respectively). |
| Missing outcome data |
High |
Comment: 43 patients randomized; 41 patients analyzed.
1 patient excluded due to humoral immune deficiency post CAR T therapy and 1 patient withdrew consent. For outcome time to viral negative conversion, 17 participants analyzed; the remaining participants tested negative at baseline. Missingness due to documented reasons unrelated to the outcome. Risk assessed to be low for the outcomes: Mortality. Time to death. Time to viral negative conversion. Incidence of clinical improvement. Time to clinical improvement. Adverse events. Serious adverse events. For WHO score 6 and above and WHO score 7 and above, 38 participants analyzed at day 28 (retrieved from contact with authors). Reason for missingness unclear. It could depend on its true value but there is no information. Risk assessed to be high for outcomes: WHO score 6 and above. WHO score 7 and above. |
| Measurement of the outcome |
Some concerns |
Comment: No information on blinding of outcome assessors
Mortality and viral negative conversion are observer-reported outcomes not involving judgement. 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: Mortality. Time to death. WHO score 7 and above. Time to viral negative conversion. Clinical improvement (defined as 2-point improvement on scale) and WHO score 6 and above requires clinical judgement and could be affected by knowledge of intervention receipt. Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected outcomes. All these outcomes 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: Incidence of clinical improvement. Time to clinical improvement. WHO score 6 and above. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol was available but did not provide enough information about the planned statistical analysis. The statistical analysis plan was not available. Risk assessed to be some concerns for the outcomes: Mortality. Clinical improvement incidence. Time to clinical improvement. Time to viral negative conversion. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |