| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: “Randomization was performed using a web-response system after stratification by COVID-19 severity (mild or moderate), age, and CT severity at enrollment.”
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Some concerns |
Quote: “multicenter, open-labeled, randomized, active-controlled phase 3 trial”
Comment: Unblinded study. No participant cross-over. No information on administration of co-interventions of interest: biologics, antivirals and corticosteroids; antivirals were part of standard of care, but no information is reported on who received these. Data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
Low |
Comment: 168 patients randomized; 168 patients analyzed.
9 patients discontinued the study. Reasons provided for missing data: withdrew consent Missingness does not depend on the true value of the outcome. Risk assessed to be low for the outcomes: Incidence of viral negative conversion. Time to viral negative conversion. Clinical improvement. Time to clinical improvement. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Unblinded study
Viral negative conversion is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Incidence of viral negative conversion. Time to viral negative conversion. Clinical improvement (defined as a reduction of patient clinical status on at least 1 score according to WHO 8-Category Ordinal Scale for Clinical Improvement) 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: Clinical improvement. Time to clinical improvement. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: Neither the protocol nor the statistical analysis plan was available at time of data extraction. The registry was available and utilized.
The outcomes related to time to viral negative conversion, time to clinical improvement, adverse and serious adverse events were registered just as reported. 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: Time to viral negative conversion. Time to clinical improvement. Adverse events. Serious adverse events Some timepoints for the outcomes of clinical improvement and viral negative conversion reported in the paper were not registered. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial was not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion. Clinical improvement. |
| Overall risk of bias |
Some concerns |