Human challenge studies in the study of infectious diseases
What can deliberately infecting healthy people tell us about infectious diseases? How is this useful for developing treatments, and how do we manage the risks?
The COVID-19 vaccination programme launched in January 2021. All adults over 18 have now been offered the vaccine, although it was reported that 1.3 million people who had been offered a vaccine had not received it. Some people are vaccine hesitant whilst others experience barriers to accessing vaccines. Targeted interventions have been promoted locally and nationally to improve vaccine uptake.
DOI: https://doi.org/10.58248/RR70
The national COVID-19 immunisation programme began in December 2019. It was designed to balance protecting the people most vulnerable to the disease against the need to deliver a national programme quickly and practically. The approach is vaccinating groups of the population to reflect age-related risk. There are two phases:
Public Health England estimated that 13,200 deaths and 39,700 hospitalisations have been prevented following the launch of phase 1 and 2. In April, the Joint Committee on Vaccination and Immunisation (JCVI) published their advice for phase 2 of COVID-19 vaccinations for all adults aged over 18. To vaccinate adults as quickly as possible, the programme will continue to offer vaccines by age cohorts rather than subgroups based on other risk factors:
The JCVI identified the following groups to be at higher risk of morbidity and mortality from COVID-19 and advised public health services to prioritise and promote vaccination to these individuals:
In March 2021 SAGE discussed the risk of a third wave of COVID-19 infections among vulnerable groups who are not directly protected, either because they are not vaccinated or because the vaccine offers insufficient protection. Depending on regional and local-level vaccine coverage, vulnerable groups may be indirectly protected by the wider vaccine uptake in the community.
However, if there are communities with lower vaccination levels, they may be more susceptible to infection and disease. Consequently, the dose schedule was changed to accelerate 2nd doses and therefore increase two dose coverage.
Vaccine coverage is a term used to describe how many people in a population have received a specific vaccine. Vaccination coverage data is important; when a larger proportion of the population is vaccinated, the more protected it is.
COVID-19 vaccines reduce the risk of infection, transmission, severe morbidity and mortality (See POST Rapid Response COVID-19 vaccines and impact on transmission). The current UK approved COVID-19 vaccinations require two doses of a COVID-19 vaccine, given on separate occasions, to afford the highest level of protection. PHE cites evidence (June 2021) that shows a single dose is between 55-70% effective against symptomatic disease.
In England, as of 1 July 2021, the Government coronavirus data dashboard showed that for adults over 18 years:
This data is updated daily on the dashboard and can be sorted according to region.
NHS England collects data on COVID-19 vaccinations for people aged 18 and over. There are geographic differences in coverage.
As of 1 July 2021, the lowest coverage rates were in London where 62.5% of adults had received one dose and 41.2% had received two doses. Coverage rates increase to 79.2% and 60.6% in the North East of England, with the highest rates of coverage seen in the South Western region with 81.5% having received one dose and 61.6% receiving two doses.
The ONS reported on vaccine coverage on 15 May 2021. It found that disparities are associated with:
An Understanding Society UK study (April 2021) found that disparities were also associated with pre-pandemic mental and physical health diagnosis. Individuals who have been prioritised for COVID-19 vaccinations due to physical medical conditions were more likely to accept the vaccine.
There are numerous reasons why someone may have chosen not to be vaccinated or to have delayed their vaccination. These include barriers to access and attitudes towards a vaccine including vaccine hesitancy.
The ONS reports on barriers to COVID-19 vaccination and other studies (including the Nuffield Council on Bioethics report on vaccine access and uptake) show that individuals’ access to vaccination are influenced by numerous factors:
Some of these barriers are common and have been documented in previous vaccination programmes as highlighted in the PHE immunisation inequalities strategy (2021).
Attitudes to COVID-19 vaccination have changed over the course of the pandemic. Data from the ONS recorded from January 2021 to May 2021 show that COVID-19 vaccine hesitancy has decreased, and positive attitudes around vaccines increased in the first three months of the COVID-19 vaccine rollout. Research from the Ipsos MORI UK Knowledge Panel confirms an increase in vaccine confidence and shows a month-by-month increase in willingness to be vaccinated (December 2020 to March 2021). Vaccine confidence refers to the level of trust individuals have towards vaccination.
In a study by the University of Oxford in autumn 2020, 58.1% of ethnic minority participants were likely or very likely to take the vaccine, and this increased to 80.5% by February 2021 after the vaccination programme began.
Understanding Society’s UK longitudinal study investigating the predictors of COVID-19 hesitancy (see definition of longitudinal studies here) identified a number of characteristics associated with increased vaccine hesitancy: lower educational attainment; coming from an ethnic minority group; being younger; being female; and coming from a socioeconomically deprived background. These findings have been reflected in many other surveys.
The Opinions and Lifestyle ONS Survey May 2021 found that:
A paper prepared by SPI-B (Independent Scientific Pandemic Influenza Group on Behaviours) for SAGE analysed a series of data and made a recommendation to examine vaccination rates in more nuanced subgroups moving beyond broader categories like age or ethnicity to understand more clearly the factors influencing vaccine uptake and to develop better messages.
The ONS commissioned an in-depth qualitative study carried out by IFF Research that investigated vaccine refusal and uncertainty amongst 50 individuals, between February and March 2021 in the UK. It included individuals who were parents, on a lower income, who had low education attainment, belonged to an ethnic minority or were clinically vulnerable. Research suggests that factors affecting COVID-19 hesitancy include:
The Nuffield study set out several strategies being used by different governments to address barriers and to improve access to vaccines. These strategies include education, information campaigns and policies that aim to incentivise vaccination or penalise those who do not get vaccinated (such as by restricting access to certain services).
The evidence of using simple and positive information as a technique to improve vaccine sentiment was reported in a randomised control trial studying the effects of different types of written vaccination information on COVID-19 vaccine hesitancy in the UK (OCEANS-III). This provided evidence on how providing in-depth information on a personal level increases the vaccine confidence and willingness across all participants including those from different ethnic and socioeconomic backgrounds. There is are also some research suggesting interventions which protect against online misinformation (See POST Rapid Response COVID-19 vaccine misinformation) .
The Government’s equalities office published the second quarterly report on progress to address COVID-19 health inequalities (March 2021), summarising target interventions for COVID-19 vaccinations. It also reports on government pilots of community-led, localised, asymptomatic testing at places of worship in ethnically diverse areas with the aim of removing some of the main identified barriers to engaging with Test and Trace, including trust and access. The success of community approaches to testing engagement could offer a model for improving vaccine coverage.
However, the Healthwatch report cautioned that targeted communication campaigns can be “counter-productive”. It noted that some Black and Asian individuals had felt that information aimed at them had created a “sense of blame” and in some it had raised suspicions about the motivations behind the campaign. It reported that pressure to get the vaccine “felt very oppressive for some”.
In February 2021 the Government published the UK COVID-19 vaccine uptake plan. This described the four key “enablers” to improving vaccine uptake across all communities:
The Government is also reviewing whether COVID-status certification or “vaccine passports” could be used to enable access to settings or to reduce restrictions. The consultation closed in March 2021, the review has not yet been published. The Government also ran a consultation on potential vaccine mandates for staff working with individuals of older adult care residents, which closed in May 2021. The Government responded to the consultation on 16 June. It stated that it will be bringing forward regulations to require all Care Quality Commission-regulated service providers of nursing and personal care, in care homes in England, to allow entry to the premises only to those who can demonstrate evidence of having had a complete course of an authorised COVID-19 vaccine. Entry will also be allowed for those with evidence that they are exempt from vaccination.
Some experts have raised concerns that vaccine passports could inadvertently discriminate or exacerbate existing inequalities and vaccine hesitancy. For example, if people for whom vaccination is unacceptable, untested, inaccessible, or impossible are denied access to essential goods and services. Some experts claim that it will have ‘significant implications across a wide range of legal and ethical issues. They argue that these examples signal the need for alternatives and exemptions (see COVID-19 vaccines and virus transmission).
The Local Government Association has produced a briefing on guidance and recommendations for local authorities on increasing uptake for COVID-19 vaccinations with key guiding principles being to ‘engage to understand, engage to empower and engage to evaluate’.
In order to improve public health communications with those communities most at risk from COVID-19, the Government released £23.75 million in funding in February 2021 to local authorities under the Community Champions scheme. This funding is to enable local authorities to work with community groups to tailor public health communications and to use trusted local voices to promote healthy living, encourage vaccine uptake and counter misinformation. This seeks to complement current communication campaigns aiming to engage with all communities through champions. For example, the London Borough of Southwark introduced vaccine vans and pop-up clinics in mosques and churches to reach people in familiar local locations. This approach has now been implemented by other local authorities.
The UK Government recently announced a partnership with dating apps to improve vaccine uptake. This includes online communications and online rewards and bonuses such as extra credits to boost an individual’s profile and show an individual’s support for vaccination.
The NHS has enrolled celebrities to influence and increase COVID-19 vaccine uptake in particular groups as well as the general public. A video and signed open letter featuring high profile individuals from Black British and Asian backgrounds was released to increase engagement amongst those communities – although concerns have been raised about the effectiveness of this approach as mentioned in the Healthwatch report.
A prospective 18-month research study funded by the UK Research and Innovation’s Economic and Social Research Council has been approved and will investigate the factors limiting vaccine uptake in minority ethnic groups through interviews and focus groups with community members. This in-depth exploration aims to use a behavioural sciences framework to evaluate campaigns across the UK and ‘develop evidence-based messaging which support vaccination decision making.’
POST would like to thank Dr Ben Kasstan (University of Bristol) and Dr Keri Wong (University College London) who acted as external peer reviewers in preparation of this article.
A correction was made on 06.07.2021. POST corrected a sentence in the section on reasons for vaccine hesitancy under the subsection of safety and risks. It previously read ‘Participants were also concerned about the potential impact of vaccines on fertility. Safety concerns and impacting fertility was also a reason stated in participants of the UCL-Penn Global COVID study and the Healthwatch report’ and now reads ‘In the UCL-Penn Global COVID study, safety concerns and side-effects were a key reason that study participants gave as the reason why they were unsure about taking the vaccine. In the Healthwatch report, participants were also concerned about the potential impact of vaccines on fertility.’ Under the same section, under the subheading ‘information’, in the second bullet point, a sentence was added at the end which states ‘Similar concerns were presented in the UCL-Penn Global COVID-19 study’. These changes were applied to improve the accuracy of citations regarding the data and information produced from the studies cited in the rapid response.
What can deliberately infecting healthy people tell us about infectious diseases? How is this useful for developing treatments, and how do we manage the risks?
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