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 |
Some concerns |
Quote: Phase II, randomized, placebo-controlled clinical trial. Participants fulfilling the eligibility criteria were randomized into the four treatment groups.
Comment: Allocation sequence probably random. No information on allocation concealment. |
| Deviations from intervention |
Low |
Quote: Single (participant).
Comment: Single blinded study (participants; not carers or personnel further involved in intervention) Deviations from intended intervention arising because of the study context: No participant cross-over. No co-interventions of interest (vaccines) were available at the time of the study. Hence, deviations did not arise 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 low for the outcomes: Symptomatic or asymptomatic confirmed COVID-19. Symptomatic confirmed or probable COVID-19. Confirmed COVID-19. ICU admission or death. Mortality. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 200 participants randomized; 200 participants analyzed.
Data available for all or nearly all participants randomized (varies by ouctomes). Risk assessed to be low for the outcomes: Symptomatic or asymptomatic confirmed COVID-19. Symptomatic confirmed or probable COVID-19. Confirmed COVID-19. ICU admission or death. Mortality. Serious adverse events. |
| 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, CONFIRMED COVID br/>Confirmed COVID and mortality are observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Confirmed COVID-19. Mortality. ICU ADMISSION OR DEATH For this outcome, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: ICU admission or death. SYMPTOMATIC OR ASYMPTOMATIC COVID, SYMPTOMATIC CONFIRMED OR PROBABLE COVID Incidence of symptomatic COVID-19 may contain clinically-detected and patient-reported outcomes which can be influenced by knowledge of intervention assignment but is not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Symptomatic or asymptomatic confirmed COVID-19. Symptomatic confirmed or probable COVID-19. SERIOUS ADVERSE EVENTS The authors reported on 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: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective trial registry was available (dated April 20th, 2020).
Outcome pre-specified. 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: Symptomatic or asymptomatic confirmed COVID-19. Symptomatic confirmed or probable COVID-19. Confirmed COVID-19. ICU admission or death. Mortality. Serious adverse events. |
| Overall risk of bias |
Some concerns |