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 |
Low |
Quote: The randomization lists were generated by an independent statistician using SAS software (version 9.4) and the randomization was performed with an interactive web response randomization"
Comment: Allocation sequence random Allocation Allocation sequence probably concealed Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: “Both the participants and investigators were aware of the group allocation, but the
125 laboratory staff, who were responsible for the sample testing, were masked”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: Quote: "Two participants were randomly assigned to CoronaVac group but were administrated with one dose of the aerosolized Ad5-nCoV vaccine by mistake. We grouped these two participants into the aerosolized Ad5-nCoV group." This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. Per-protocol analysis was performed on the outcomes. Two participants cross-over and were not analized in the group assigned at randomization. As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was probably no substantial impact of failure to analyze participants according to their randomized assignment due to small number of paticipants involved in cross-over Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. Confirmed COVID19 severe or critical. Neutralizing antibody GMT Omicron. Seroconversion rate Omicron |
| Missing outcome data |
Low |
Comment: 420 participants randomized; 397 participants analyzed for Confirmed symptomatic COVID-19 and Confirmed COVID19 severe or critical , 416 participants analyzed for Seroconversion rate Omicron, 419 participants analyzed for Neutralizing antibody GMT Omicron
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Confirmed COVID. Confirmed COVID (partial vaccination). Confirmed symptomatic COVID. Confirmed COVID19 severe or critical. Seroconversion rate Omicron. Neutralizing antibody GMT Omicron. |
| 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) SEROCONVERSION RATE OMICRON. NEUTRALIZING ANTIBODY ASSAY GMT OMICRON Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Seroconversion rate Omicron; Neutralizing antibody GMT Omicron. CONFIRMED SYMPTOMATIC COVID-19. CONFIRMED COVID SEVERE OR CRITICAL Data available for all or nearly all participants randomized. Outcome self-reported Quote: "Each participant was interviewed by telephone, and all the information on any SARS-CoV-2 infection reported were documented by the investigators. A COVID-19 case was defined as having positive results for SARS-CoV-2 antigen rapid test or nucleic acid test with or without symptoms, or having an epidemiological exposure or contact to COVID-19 patients, combined with the presence of at least two suspicious symptoms (i.e., fever, dry throat, sore throat, cough, shortness of breath, etc.) when no laboratory results available." Assessment could be affected by knowledge of the intervention It is NOT likely that the assessment could be affected by knowledge of the intervention Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID.Confirmed COVID19 severe or critical |
| Selection of the reported results |
Some concerns |
Comment: The registry was available (January 24, 2022)
SEROCONVERSION RATE OMICRON. NEUTRALIZING ANTIBODY ASSAY GMT OMICRON 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 outcome: Seroconversion rate Omicron. Neutralizing antibody GMT Omicron. CONFIRMED SYMPTOMATIC COVID-19. CONFIRMED COVID SEVERE OR CRITICAL Outcome not pre-specified Quote: "The vaccine efficacy was a post hoc analysis that was not prespecified in the protocol" Quote: "A major outbreak of COVID-19 dominantly causing by the SARS-CoV-2 Omicron variants BA.5.2, BA.2.76, and BF.7 were emerged in China, between Nov 1, 2022 and Jan 30, 2023.12 In order to evaluate the efficacy of the boost regimen of aerosolized Ad5-nCoV versus inactivated vaccine during this outbreak period, we did a retrospective survey to identify the breakthrough COVID-19 cases from Feb 4 to March 25, 2023." No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome:Confirmed COVID19 severe or critical Confirmed symptomatic COVID. |
| Overall risk of bias |
Some concerns |