Summary of findings 14. Heterologous vaccination scheme compared to homologous vaccination scheme for vaccination against COVID‐19a.
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants | Certainty of the evidence (GRADE) | Comments | |
| Risk with homologous vaccination scheme | Risk with heterologous vaccination scheme | |||||
| Confirmed SARS‐CoV‐2 infection | Outcome not yet measured or reported | |||||
| Confirmed symptomatic COVID‐19 | Outcome not yet measured or reported | |||||
| Severe or critical COVID‐19 | Outcome not yet measured or reported | |||||
| All‐cause mortality | Outcome not yet measured or reported | |||||
| Systemic reactogenicity eventsb | 60 per 1000 | 118 per 1000 (31 to 445) | RR 1.96 (0.52 to 7.41) | 101 (1 RCT)c | ⊕⊕⊖⊖ Lowd,e | — |
| Any adverse eventf | 3 studies (n = 564) that compared heterologous versus homologous vaccination schemes reported any adverse event with 1 or 2 months' follow‐up. 2 of the studies reported an effect estimate in favour of homologous scheme but with CIs crossing the line of no effect (RR 1.21, 95% CI 0.87 to 1.68; n = 234; and RR 1.03, 95% CI 0.75 to 1.43; n = 229). 1 study reported an effect estimate in favour of homologous scheme with CIs not crossing the line of null effect (RR 3.19, 95% CI 1.11 to 9.11; n = 101) | — | (3 RCTs)g | ⊕⊖⊖⊖ Very lowh,i,j | — | |
| Serious adverse eventsk | 1 study (Liu 2021: ChAdOx1/BNT162b2 versus ChAdOx1/ChAdOx1) that compared heterologous versus homologous vaccination schemes reported no serious adverse events in the heterologous scheme (0/114) versus 1 serious adverse event (1/115) in the homologous scheme (RR 0.34, 95% CI 0.01 to 8.17). 2 more studies reported the outcome, with 0 events in both groups: Li 2021a: CoronaVac/Ad5 versus CoronaVac/CoronaVac in n = 51 versus n = 50 and Liu 2021: BNT162b2/ChAdOx1 versus BNT162b2/BNT162b2 in n = 115 versus n = 119 respectively, in heterologous versus homologous scheme | — | 229 (1 RCT)l | ⊕⊖⊖⊖ Very lowh,m | — | |
| Local reactogenicity eventsb | 20 per 1000 | 235 per 1000 (32 to 1000) | RR 11.76 (1.59 to 87.14) | 101 (1 RCT)c | ⊕⊕⊖⊖ Lowd,n | — |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). COVID‐19: coronavirus disease 2019 CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2. | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
aLast updated: 4 May 2022 bFollow‐up: 28 days cLi 2021a: CoronaVac/Ad5 versus CoronaVac/CoronaVac dDespite some concerns with deviation from intended intervention, not downgraded for risk of bias. eImprecision: downgraded two levels due to wide CIs consistent with the possibility of benefit for heterologous and benefit for homologous vaccination scheme and the low number of events/participants. fFollow‐up: one and two months gLi 2021a: CoronaVac/Ad5 versus CoronaVac/CoronaVac; Liu 2021: BNT162b2/ChAdOx1 versus BNT162b2/BNT162b2; Liu 2021: ChAdOx1/BNT162b2 versus ChAdOx1/ChAdOx1 hRisk of bias downgraded one level: some concerns regarding outcome measurement. iInconsistency: downgraded one level as studies are not pooled, effect estimates and direction of effect inconsistent between included studies. jImprecision: downgraded one level due to wide CIs consistent with the possibility of no effect and benefit for homologous vaccination scheme and the low number of events/participants. kFollow‐up: one month lLiu 2021: ChAdOx1/BNT162b2 versus ChAdOx1/ChAdOx1 mImprecision: downgraded two levels due to wide CIs consistent with the possibility of benefit for the heterologous and benefit for homologous vaccination scheme and the low number of events/participants. nImprecision: downgraded two levels due to very few events or participants (or both).