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: “Patients were randomized to receive either verum auricular vagus nerve (AN) or sham (SN) neuromodulation.”
Comment: Allocation sequence probably random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: "The patients, their physicians, and nursing staff were blind about randomization because the ears were hidden by the opaque Band-Aid throughout the hospitalization"
Comment: Unclear if blinding was maintained for the duration of the study period (needles in the ear with a band aid vs. no needles with a band aid during hospitalisation, after initial procedure). Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: antivirals, biologics, and corticosteroids. Hence, no information on whether deviations arose because of the trial context. 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). Clinical improvement (D28). |
| Missing outcome data |
Low |
Comment: 29 participants randomized; 29 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28) |
| 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. Unclear blinding (outcome assessor). MORTALITY Observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as 7-category ordinal Clinical Progression Scale score improvement or Hospital discharge) 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 outcome: Clinical improvement (D28). |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (dated 10 April 2020).
CLINICAL IMPROVEMENT 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: Clinical improvement (D28) MORTALITY Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Results were probably not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcomes: Mortality (D28). |
| Overall risk of bias |
Some concerns |