Living Systematic Meta-Analysis of COVID-19 Vaccines and Dose Allocation Strategies

Background: The need to rapidly immunize the population against SARS-CoV-2 to obtain herd immunity together with shortage of vaccine supplies suggest to vaccinate the largest number of people with a single dose of vaccine delaying the second dose. Methods: The primary outcomes of our meta-analysis were the efficacy of one or both doses of vaccines in preventing COVID-19 and their safety. In addition, using a differential equation model taking into account the effects of lockdown and vaccination, we sought to study the effectiveness of one or both doses of vaccines in preventing new cases of COVID-19 in UK and Israel. These countries, where a large portion of the population is already vaccinated, have different vaccination strategies, 3 vs. 12 weeks delay between first and second dose. Findings: The first vaccine dose averted infection in 71% of participants, while the booster dose cumulatively prevented COVID-19 in 87% of participants. The pooled treatment effects in two age subgroups (<65 or ≥65 years) were not significantly different. No significant difference on efficacy between white and black or ethnic minorities was observed. Mortality was reduced by 56% after active treatment versus placebo. The pooled Risk-Ratio of experiencing a serious event after vaccination was 6%.Population data modelling show a dramatic reduction of the number of daily new cases in UK starting at 16 days after the first dose administration. Notably, the number of dose-1 daily administrations explains the observed reduction of daily new cases in UK and is able to predict new observations with high certainty. In Israel, the effects of the first dose of vaccine in reducing the incidence of COVID-19 was virtually immediate. Interpretation: Our RCT meta-analysis and population-based analysis show that the first dose of COVID-19 vaccines averts infection in almost 3/4 of subjects and suggest that postponing the second dose by at least 12 weeks is a suitable strategy that allows vaccinating more people, substantially increasing the benefits of vaccines. Funding Statement: There was no external funding source for this study. Declaration of Interests: All authors declare no competing interests: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work; no other relationships or activities that could appear to have influenced the submitted work.