ABSTRACT
IntroductionIn 2020, the UK Health Security Agency (UKHSA) established a large-scale testing programme to rapidly identify individuals in England who were infected with SARS-CoV-2 and had COVID-19. This comprised part of the UK governments COVID-19 response strategy, to protect those at risk of severe COVID-19 disease and death and to reduce the burden on the health system. To assess the success of this approach, UKHSA commissioned an independent evaluation of the activities delivered by the NHS testing programme in England. The primary purpose of this evaluation is to capture key learnings from the rollout of testing to different target populations via various testing services between October 2020 and March 2022 and to use these insights to formulate recommendations for future pandemic preparedness strategy. Methods and analysisThe proposed study involves a stepwise mixed-methods approach, aligned with established methods for the evaluation of complex interventions in health, with retrospective and prospective components. A bottom-up approach will be taken, focusing on each of nine population-specific service settings. We will use a Theory of Change to understand the causal pathways and intended and unintended outcomes of each service, also exploring the effect of context on each individual service settings intended outcomes. Subsequently, the insights gained will be synthesised to identify process and outcome indicators to evaluate how the combined aims of the testing programme were achieved. A forward-looking, prospective component of this work will aim to inform testing strategy in preparation for future pandemics, through a participatory modelling simulation and policy analysis exercise. DisclaimerThis is a provisional draft protocol that represents research in progress. This research was commissioned and funded by UKHSA, to be performed between August 2022 and March 2023. The scope and depth of testing services and channels covered by this research were pre-agreed with UKHSA and are limited to the availability and provision of data available at the time this protocol was written. Ethics and disseminationFindings arising from this evaluation will be used to inform lessons learnt and recommendations for UKHSA on appropriate pandemic preparedness testing programme designs; findings will also be disseminated in peer-reviewed journals and at academic conferences. Strengths and limitations of the studyO_LIStrengths of this mixed-methods evaluation protocol include the use of theory-based, complex evaluation approaches and an iterative and participatory approach with the stakeholder (UKHSA) to the evaluation process and prospective modelling. C_LIO_LIGiven the scale and complexity of the COVID-19 testing response in England, there is a scarcity of previous relevant research into this, either in England or appropriate international comparators, warranting the mixed-methods evaluation approach we are adopting. C_LIO_LIThis is the first national-scale evaluation of the testing response to COVID-19 in England to incorporate most service settings, a programme which formed an integral part of the UK pandemic response strategy. The approach proposed could be applied to the evaluation of pandemic responses in other contexts or to other types of interventions. C_LIO_LIWhereas most complex interventions are accompanied by a prospective evaluation design initiated at the time of the intervention or earlier, this study predominantly comprises a retrospective evaluation and is therefore limited by the quality of existing research and the data available to the research team at the time of conducting the evaluation within the specified period allocated by UKHSA. C_LI
ABSTRACT
On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.
ABSTRACT
BackgroundAlthough 6 COVID-19 vaccines have been approved by the World Health Organisation as of 16th June 2021, global supply remains limited. An understanding of the immune response associated with protection could facilitate rapid licensure of new vaccines. MethodsData from a randomised efficacy trial of ChAdOx1 nCoV-19 (AZD1222) vaccine in the UK was analysed to determine the antibody levels associated with protection against SARS-CoV-2. Anti-spike and anti-RBD IgG by multiplex immunoassay, pseudovirus and live neutralising antibody at 28 days after the second dose were measured in infected and non-infected vaccine recipients. Weighted generalised additive models for binary data were applied to symptomatic and asymptomatic SARS-CoV-2 infection data from ChAdOx1 nCoV-19 recipients. Cubic spline smoothed log antibody levels, and weights were applied to account for potential selection bias in sample processing. Models were adjusted for baseline risk of exposure to SARS-CoV-2 infection. ResultsHigher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Vaccine efficacy of 80% against primary symptomatic COVID-19 was achieved with an antibody level of 40923 (95% CI: 16748, 125017) and 63383 (95% CI: 16903, not computed (NC)) for anti-spike and anti-RBD, and 185 (95% CI: NC, NC) and 247 (95% CI: 101, NC) for pseudo- and live-neutralisation assays respectively. Antibody responses did not correlate with overall protection against asymptomatic infection. ConclusionsCorrelates of protection can be used to bridge to new populations using validated assays. The data can be used to extrapolate efficacy estimates for new vaccines where large efficacy trials cannot be conducted. More work is needed to assess correlates for emerging variants.