RESUMEN
BackgroundThe UK was the first country to start national COVID-19 vaccination programmes, initially administering doses 3-weeks apart. However, early evidence of high vaccine effectiveness after the first dose and the emergence of the Alpha variant prompted the UK to extend the interval between doses to 12-weeks. In this study, we quantify the impact of delaying the second vaccine dose on the epidemic in England. MethodsWe used a previously described model of SARS-CoV-2 transmission and calibrated the model to English surveillance data including hospital admissions, hospital occupancy, seroprevalence data, and population-level PCR testing data using a Bayesian evidence synthesis framework. We modelled and compared the epidemic trajectory assuming that vaccine doses were administered 3-weeks apart against the real vaccine roll-out schedule. We estimated and compared the resulting number of daily infections, hospital admissions, and deaths. A range of scenarios spanning a range of vaccine effectiveness and waning assumptions were investigated. FindingsWe estimate that delaying the interval between the first and second COVID-19 vaccine doses from 3- to 12-weeks prevented an average 64,000 COVID-19 hospital admissions and 9,400 deaths between 8th December 2020 and 13th September 2021. Similarly, we estimate that the 3-week strategy would have resulted in more infections and deaths compared to the 12-week strategy. Across all sensitivity analyses the 3-week strategy resulted in a greater number of hospital admissions. InterpretationEnglands delayed second dose vaccination strategy was informed by early real-world vaccine effectiveness data and a careful assessment of the trade-offs in the context of limited vaccine supplies in a growing epidemic. Our study shows that rapidly providing partial vaccine-induced protection to a larger proportion of the population was successful in reducing the burden of COVID-19 hospitalisations and deaths. There is benefit in carefully considering and adapting guidelines in light of new emerging evidence and the population in question. FundingNational Institute for Health Research, UK Medical Research Council, Jameel Institute, Wellcome Trust, and UK Foreign, Commonwealth and Development Office, National Health and Medical Research Council. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed up to 10th June 2022, with no language restrictions using the following search terms: (COVID-19) AND (vaccin*) AND (dose OR dosing) AND (delay OR interval) AND (quant* OR assess* OR impact). We found 14 studies that explored the impact of different vaccine dosing intervals. However, the majority were prospective assessments of optimal vaccination strategies, exploring different trade-offs between vaccine mode of action, vaccine effectiveness, coverage, and availability. Only two studies retrospectively assessed the impact of different vaccination intervals. One assessed the optimal timing during the epidemic to switch to an extended dosing interval, and the other assessed the risk of all-cause mortality and hospitalisations between the two dosing groups. Added value of this studyOur data synthesis approach combines real-world evidence from multiple data sources to retrospectively quantify the impact of extending the COVID-19 vaccine dosing interval from the manufacturer recommended 3-weeks to 12-weeks in England. Implications of all the available evidenceOur study demonstrates that rapidly providing partial vaccine-induced protection to a larger proportion of the population was successful in reducing the COVID-19 hospitalisations and mortality. This was enabled by rapid and careful monitoring of vaccine effectiveness as nationwide vaccine programmes were initiated, and adaptation of guidelines in light of emerging evidence.
RESUMEN
The worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extended a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO-developed target product profiles. We identified optimal vaccine allocation strategies within- and between-countries to maximise averted deaths under constraints on dose supply. We found that the health impact of SARS-CoV-2 vaccination depends on the cumulative population-level infection incidence when vaccination begins, the duration of natural immunity, the trajectory of the epidemic prior to vaccination, and the level of healthcare available to effectively treat those with disease. Within a country we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly. However, with a larger supply, if vaccination can occur while other interventions are maintained, the optimal strategy switches to targeting key transmitters to indirectly protect the vulnerable. As supply increases, vaccines that reduce or block infection have a greater impact than those that prevent disease alone due to the indirect protection provided to high-risk groups. Given a 2 billion global dose supply in 2021, we find that a strategy in which doses are allocated to countries proportional to population size is close to optimal in averting deaths and aligns with the ethical principles agreed in pandemic preparedness planning. HighlightsO_LIThe global dose supply of COVID-19 vaccines will be constrained in 2021 C_LIO_LIWithin a country, prioritising doses to protect those at highest mortality risk is efficient C_LIO_LIFor a 2 billion dose supply in 2021, allocating to countries according to population size is efficient and equitable C_LI
