| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: "Randomization sequence was prepared by a centralized, web-based system in blocks of variable size (3, 6 or 9 cases per block) and communicated to the trial physicians that recruited the patients upon entry to the web system information on availability of the signed Informed Consent Form and verification of all eligibility criteria." Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “Patients, nurses, and physicians were not blinded to the treatment arm. Outcome assessors (virology staff) were blinded to the treatment group by receiving the samples labeled with randomization code and visit number."
Comment: Single-blinded study (outcome assessors), which is relevant to viral load outcome only. Unblinded for outcomes extracted No participant crossover. No information on administration of co-interventions of interest: antivirals, corticosteroids, biologics. All participants assigned to the treatment group started treatment, therefore the adverse events included all participants. |
| Missing outcome data |
Low |
Comment: 45 patients randomized; 32 patients analyzed for WHO score 7 and above. 45 patients analyzed for mortality, adverse events and serious adverse events.
Missingness not likely related to the outcome for WHO score 7 and above. Reasons of exclusions reported could not be related to outcomes: viral load below limit of quantification at baseline (ineligible patients at baseline), withdrew consent and poor quality samples. Risk assessed to be low for the outcomes: Mortality. WHO score 7 and above. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Unblinded study for outcomes of interest.
Mortality is an observer-reported outcome not involving judgement. For the incidence of 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. WHO score 7 and above. 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: Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: Outcomes reported as pre specified in the registry. Neither the protocol nor the statistical analysis plan was available.
Risk assessed to be low for the outcomes: Mortality. WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |