Coronavirus (COVID-19) vaccine barriers and incentives to uptake: literature review

Confidence

Confidence relates to the issue of trust, both in vaccine effectiveness and safety, and in the political and medical professionals and systems that deliver it. These aspects are explored in the sub-sections below.

Trust in vaccine safety/effectiveness

The issue of trust in Covid-19 vaccines originates from concerns about their side effects (including long-term side effects), their effectiveness (e.g. due to the emergence of new variants), and the thoroughness of research trials and quality standards in vaccine production (given the unparalleled speed at which vaccines have been developed).

These concerns have been seen in sub-groups of the Scottish population. Data from the Scottish Government's YouGov polling reveal that, in April 2021, 47% of those who rated themselves as less likely to receive a vaccine reported 'being concerned about the safety of vaccines' as one of the main deterrents to uptake^[91]. More recently, in January 2022, 29% of the hesitant indicated concerns about having a reaction to or feeling unwell because of the vaccine as reasons for not wanting to get a booster^[92], with 54% of parents of 5-11 year olds expressing worries about the safety of the vaccine in March 2022^[93]. Additionally, an analysis of public and stakeholders' responses submitted to the Scottish Government between August and September 2021 on the approach to establishing the Covid-19 Scottish Inquiry highlighted concerns about vaccine safety, vaccine efficacy for immunosuppressed groups and decision making around the vaccination of young people^[94].

A substantial number of UK studies also identify worries about known or unforeseen side effects as one of the main reasons for vaccine hesitancy. For example, data on 32,361 UK adults drawn from the COVID-19 Social Study – a large panel study of psychological and social experiences of the pandemic that commenced in March 2020 – show that hesitancy was mostly related to mistrust about vaccine safety and concerns about unforeseen side effects^[95]. In the UPTAKE study, a cross-sectional online survey administered between September and October 2020, 60% of respondents indicated the risk of side effects as the main reason for wanting to refuse a Covid-19 vaccine^[96]. Similarly, a cohort study exploring reasons for vaccine hesitancy in 1,254,294 UK participants reported long-term effects and adverse reactions as main reasons^[97]. Finally, in a cross-sectional questionnaire conducted among undergraduate students at a British university in June 2021, worries around side effects were significantly associated with vaccine hesitancy, with a substantial percentage of students willing to be vaccinated (54%) concerned about the safety of the vaccines too^[98].

Research conducted even before the deployment of the vaccines provided similar findings. The UK Household Longitudinal Study (also known as the Understanding Society study) reported that concerns over unknown effects were the main deterrent to vaccination for 42.7% of participants, with significant differences by minority ethnic group. Black and Black British respondents were more likely than the White British and Irish grouping to state that they didn't trust vaccines (29.2% vs 5.7%). Pakistani and Bangladeshi respondents, instead, mentioned concerns about side effects more often than the White British and Irish group (35.4% vs 8.6%). Although 43.2% of the Black and Black British respondents thought nothing could change their mind about whether or not to take up the vaccine, 44.7% said they could re-consider their decision if the vaccine was proved to be safe (a percentage that reached 64.6% in the Pakistani/Bangladeshi group)^[99].

Qualitative research provides further insights. In a mixed method study carried out in December 2020, a number of participants stated that they found it hard to believe that appropriate standards were followed in the testing and production of vaccines, with some wanting to wait and see whether longer-term effects would affect those accepting them. A correlation between Covid-19 vaccine hesitancy and engagement with other vaccination campaigns also emerged, sometimes linked by the respondents to experiences of adverse reactions to other vaccines^[100]. Likewise, engagement work with over 200 community organisations offering support to ethnic minorities found that safety and potential long-term effects on health were a recurrent theme: minority ethnic groups expressed a need for equal representation in clinical trials and for clearer advice, with misinformation on social media said to reduce confidence in the vaccines; older individuals were particularly concerned about the risk of developing blood clots following vaccination with AstraZeneca, while younger women worried about links between the vaccine and infertility^[101].

Overall, data on vaccine uptake show that pregnant women tend to register higher levels of hesitancy and low confidence in the Covid-19 vaccines in the UK population, especially if they belong to minority ethnic groups or they live in the most deprived areas^{[102] [103]}. This trend was anticipated by a large multinational cross-sectional study conducted between June and July 2020, hence prior to the rollout of Covid-19 vaccines: pregnant and breastfeeding women were found to be vaccine hesitant, in particular if they were unemployed and with low or medium levels of education, highlighting the existence of both social and gender-based health inequalities^[104]. Similarly, a mixed-method study conducted between August and October 2020 revealed that vaccine acceptance was significantly lower during pregnancy, although finding that Scottish women were almost twice as likely to accept a vaccine for their baby compared to English women^[105].

In qualitative work conducted with pregnant women, concerns about vaccine novelty and safety (both for themselves and their baby) also appear as reasons for reluctance to participate in clinical trial^[106], in line with historical trends of the scarce presence of women of reproductive age in pharmaceutical research^[107]. Hesitancy among pregnant women to take part in trials could be partly attributed to changing guidance and advice from the JCVI^{[108] [109]}. Initially, this group was not recommended a vaccine, given the limited data on vaccine safety during pregnancy. However, as more trials commenced and the risk of severe disease outcomes in this cohort became clearer, the JCVI modified its position and recommended jabs for pregnant women based on their age and clinical risk group on the same basis as the rest of the population.

A good number of studies in the literature explore the issue of trust in vaccine safety and effectiveness among health and social care workers. For example, a survey administered by Public Health Scotland in March 2021 to over 7000 healthcare and social care staff found that worries about both immediate and future unknown side effects were the most frequently selected reasons for refusing a vaccine, with participants indicating in free text that pregnancy, trying to conceive or breastfeeding, together with allergies, were a factor^[110]. A single centre cohort study conducted among healthcare workers in a London hospital also found that concerns around immediate (e.g. allergic reaction) and long-term side effects (especially on pregnancy and fertility) were commonly shared reasons for refusing the vaccine. This was the case especially among nursing, clinical support, portering, domestic and catering staff, and in Black, Afro-Caribbean and mixed heritage participants^[111]. When care home staff in the Liverpool City Council region were surveyed in January 2021, they also indicated concerns about lack of research into vaccine safety as a reason for vaccine refusal^[112].

Qualitative work supports these findings. Data collected between December 2020 and March 2021 for the UK-REACH study identified concerns about vaccine safety/efficacy as a main contributor to hesitancy in healthcare settings. These concerns derived both from the speed of vaccine development and the lack of participation of ethnic minorities in trials, and from the overwhelming amount of complex and sometimes conflicting information in a limited number of languages^[113]. Furthermore, in-depth interviews carried out among healthcare staff for the TIDES study between October 2020 and January 2021 showed how hesitancy was related to fear of harm to self, often unspecified but including effects on fertility and the possibility of developing Covid-19 symptoms amongst other things. This fear was primarily linked to concerns about the speed at which vaccines were developed and deployed, and the lack of clinical evidence on the longer-term effects^[114].

In some studies, underlying conditions or a weak immune system (e.g. due to a cancer diagnosis or the use of immunosuppressant drugs) have been linked to hesitancy and lack of confidence in Covid-19 vaccines^{[115] [116]}. A survey aiming to gather insights on the lived experiences of those shielding in Scotland received 4590 responses between December 2020 and January 2021: among the 11% still undecided whether to get the vaccine, concerns about side effects (62%), worries that the vaccine hadn't been tested on people with their health condition (52%) and a desire to wait until others have had it first (30%) were indicated as main reasons^[117]. Moreover, a retrospective cohort study assessing vaccine acceptance among 2,183,939 eligible individuals in North West London between the beginning of the vaccination campaign and February 2021 found not only that Black and Black British people had the highest rate of declining a vaccine, but that those clinically extremely vulnerable within this group had the highest percentage of hesitancy^[118]. Healthcare staff interviewed as part of the TIDES study also spoke of worries about side effects in relation to their underlying health conditions^[119]. Finally, secondary analysis of data from the longitudinal study Understanding Society highlighted how the most common reason for hesitancy among people with disabilities was a concern about the future effects of the vaccines, followed by lack of trust in the vaccines and concerns about immediate side effects^[120].

The studies presented in this section have been conducted at different points in time. Emerging science and changing guidance have impacted their results, as the vaccination campaign progressed and both clinical and real-life data contributed to shape the government's response (e.g. regarding recommendations for pregnant women and children). The association of AstraZeneca with rare blood clots, and of Moderna and Pfizer with myocarditis and pericarditis (two forms of heart inflammation) proved a challenge for the promotion of vaccine safety. On the other hand, as further research became available and the vaccines started to be widely distributed globally, perceptions of personal harm changed. A poll conducted by IPSOS shows how the percentage of Britons thinking that there had not been enough time to observe vaccine side effects decreased from 61% in November 2020 to 41% in May 2021. Over the same period of time, the number of those thinking that there had not been enough time to assess whether the vaccine works went from about half of the sample to just one third. Although 48% of respondents had concerns over vaccine effectiveness against new variants in May 2021, overall confidence was high and 94% of the sample stated they had received the vaccine or planned to do so^[121].

The complexity of this landscape should be noted. Since the beginning of the pandemic the public have been constantly receiving a significant number of messages on the clinical characteristics and efficacy of multiple vaccines, immune response, duration of immunity and need for further doses, hence facing what WHO's director-general Tedros Adhanom Ghebreyesus has called an 'infodemic'^[122]. Infodemic refers to the overabundance of information in both physical and digital environments during a disease outbreak, which causes confusion and ultimately "leads to mistrust in health authorities and undermines the public health response"^[123]. It has been observed how social media has heavily contributed to the public's confusion over vaccine safety, by becoming a fertile ground for misinformation as well as the preferred platform for the anti-vaxx movement^[124]. False information claiming to be based on science has been circulating widely, with platforms adapting content feeds to individual preferences and exposing users to echo chambers, where pre-existing beliefs are reinforced and the ability to discern reliable from unreliable sources is reduced^{[125] [126]}.

Together with general attitudes to vaccines, conspiracy suspicions have been found to be one of the strongest predictors of vaccine hesitancy^{[127] [128] [129]}. Myths and hoaxes have proliferated, presenting frequent changes to guidance as proof of health and political authorities' failures and using emotive stories to play on people's anxieties and fears^[130]. A randomised controlled trial conducted in the US and in the UK examined the link between vaccine hesitancy and exposure to online misinformation, and found that the latter lowered intention to get a vaccine by 6.2 percentage points in the UK^[131]. The literature not only shows that ethnic minorities are more likely than White British groups to be exposed to misinformation originating both from social media or word of mouth, with family and country of origin playing a significant role^[132], but that they are also more than twice as likely to share content about safety concerns on the vaccine^[133].

Recommendations to improve confidence in vaccine safety and effectiveness in the sources examined here include the promotion of a direct and two-way dialogue with different groups and communities in order to meet specific needs, while educational campaigns and initiatives to target misinformation have been indicated as a form of intervention that has already shown positive results^{[134] [135]}. Some have suggested that social media companies should exert greater control on their platforms and remove posts or accounts spreading misinformation^{[136] [137]}. In England, the government has launched a social media toolkit empowering the targeted audiences to spot dubious content and check authenticity of information^[138]. Informing the public about the rarity of some side effects and explaining that they are also (potentially significant) Covid-19 symptoms (e.g. blood clots), and restating that the benefits of getting vaccinated outweigh the risks of catching the virus have also been deemed necessary steps^[139]. Further research into reported side effects such as menstrual changes after vaccination could also help dispel fears related to fertility^[140]. Moreover, questioning the systematic exclusion of pregnant women from clinical trials could lead to better data, higher uptake and health professionals' increased confidence in recommending vaccines^[141]. Finally, there has been a focus on the role that medical professionals could play in the provision of information about clinical trials and the regulatory process, together with their own experience of vaccination^{[142] [143] [144]}.

Trust in the political and medical system

Hesitancy has also been linked in the literature to lack of trust in the system that delivers the vaccines. This system extends from government institutions and health care providers to the scientific community and Big Pharma. Distrust in the companies that produce the vaccines and the agencies overseeing their development has often been fed by conspiracy theories on falsification or concealment of data for financial gain or political objectives^[145].

Data from a mixed method study carried out in December 2020 reveal a correlation between hesitancy and low levels of trust in authorities, with odds ratios of vaccine refusal being higher in the 29.7% of the sample believing that the UK Government never or almost never told the truth about Covid-19. Respondents mentioned alleged personal financial gain for ministers and provision of legal indemnities to pharmaceutical companies^[146]. Similarly, a cross-sectional representative survey administered in January and February 2021 to 4978 UK adults reports that, while around 80% of respondents trusted NHS and scientific professionals, just 44% said they trusted the UK Government^[147]. Free text comments left by respondents of the UPTAKE study mentioned mistrust around government strategies and the belief that ethnic minorities were being used to test vaccines^[148]. In Wales, a national telephone survey also found that those who had low trust in NHS Covid-19 information were more likely to report vaccine hesitancy (42.1% vs 5.6% of those without low trust)^[149].

A number of studies focus on the views and experiences of healthcare staff as one of the priority groups for vaccination. Healthcare workers who participated in the prospective cohort study UK-REACH between December 2020 and March 2021 indicated lack of trust in the UK Government and their employers as main contributors to hesitancy. Despite relying on the information provided by government or NHS sources, some reported that they presented vaccines in a too positive light and associated risks were not transparently communicated. Others expressed discomfort with media and campaign messages portraying ethnic minorities as hesitant and with the idea of mandatory vaccinations for those working in healthcare settings, both seen as a cause of divides between communities and increased stigma^[150]. When the UK-REACH data was analysed in April and June 2021, researchers found that there was persistent hesitancy in a minority of healthcare workers^[151]. Furthermore, in the qualitative interviews conducted for the TIDES study, vaccine hesitancy was linked by minority ethnic healthcare staff to structural discrimination and racism, in particular to concerns around institutional pressure to be vaccinated (perceived as a deprivation of individual autonomy), inequalities in the development and testing of vaccines, and religious or ethical implications of accepting a vaccine. Some research participants mentioned past vaccines or treatment roll-outs known to have substantially harmed the population such as Thalidomide, a drug prescribed in the 1950s to treat morning sickness in pregnant women which was found to have caused severe and debilitating malformations in over 10,000 newborns^[152].

Overall, the issue of trust is strongly correlated to ethnicity in the sources examined in this review. Qualitative analysis from a mixed-method study conducted among minority ethnic residents in Luton between January and March 2021 reports lack of trust in the authorities as the most common reason for refusing a vaccine, together with concerns on the speed of vaccine development^[153]. In a review of 29 articles on vaccine uptake in ethnic minorities higher hesitancy has been linked to mistrust in medical and scientific professionals and conspiracy attitudes^[154]. Similar structural barriers appear in survey data from the University College London COVID-19 Social Study collected between July 2020 and June 2021: those who refused the offer of a vaccine were nearly seven times more likely to have experienced racial discrimination in a medical setting compared to those who accepted it^[155].

In-depth interviews conducted in Bradford with minority ethnic groups also revealed how mistrust was caused by exposure to conflicting information, sometimes resulting from the diverse responses adopted by a country of origin or of close connection compared to the UK. Concerns about the association of Covid-19 vaccines with infertility emerged too, and were linked to alleged population planning. Participants mentioned rumours about certain minority ethnic groups being used to test the vaccines or being harmed on purpose through them^[156]. Similar results appear in other sources. In free text comments collected during the UPTAKE study in September/October 2020, ethnic minorities were found to perceive themselves as 'guinea pigs' in vaccine trials and were less likely than any other group to be willing to take part in them^[157]. Likewise, qualitative work with primary care professionals and migrants carried out across England between June and November 2020 reports beliefs that minority ethnic communities are underrepresented in clinical trials or exploited during those^[158]. Additionally, a nationally representative study conducted in December 2020 shows how the majority of those who refused the vaccine believed or suspected the virus was man-made and justified this belief with the disproportionate impact of Covid-19 on certain population groups^[159].

Minority ethnic communities have traditionally had low levels of vaccine uptake in the UK (e.g. MMR or HPV), MMRh because of cultural and structural racism and systematic discrimination, and underrepresentation in clinical trials^[160]. Therefore, some scholars have been sceptical about the effectiveness of any measure or initiative aiming to promote vaccine acceptance, as those who disproportionately suffered the consequences of the pandemic are asked to trust the same structures that have previously failed them^{[161] [162]}. Engagement work with organisations working with asylum seekers and migrants, for example, revealed worries of deportation following the registration for a vaccine and highlighted how deeply rooted marginalisation can be^[163]. For Black minorities, in particular, worries about the development and testing of vaccines can be particularly meaningful, as they draw from a history of unethical research and experimentation. Just to mention one example, efforts to eradicate polio in Africa recently saw the administration of a vaccine while it was still undergoing clinical trials. In 2019 this was found to have caused new infections and paralysis in 196 children across 12 countries^[164].

Possible solutions to address lack of confidence in political and medical systems suggested in the literature include: collaboration with third sector organisations^[165] and development of community networks supporting local key actors, such as religious and community leaders, teachers, and youth or sport clubs^{[166] [167] [168]}; community education carried out by healthcare professionals belonging to ethnic minorities and the administration of vaccines in the presence of trusted family physicians^[169]; training for health care professionals in culturally tailored conversations that respond to and anticipate vaccine concerns in different groups^{[170] [171]}; use of online platforms to spread vaccine information^[172] and offers of support to local leaders through training materials^[173].The importance of avoiding stigmatisation of minority ethnic groups by pressuring or singling out those communities who are hesitant has been underlined^{[174] [175]}, although in contrast with some views recommending instead a focus on these communities at higher risk of Covid-19 illness and death^[176]. It has also been highlighted how minority ethnic groups shouldn't be treated as a homogenous group, with each community presenting different levels of acceptance and specific concerns and informational needs^{[177] [178]}.

The choice of who promotes public health messaging is also crucial. A cross-cultural study carried out in the UK, US and Turkey showed that vaccination of an expert scientist was the most effective incentive to uptake in all three countries. The authors interpreted this result in relation to people's tendency to imitate highly respected individuals in a group, in this case those who are known for their knowledge of Covid-19 and vaccines^[179]. Furthermore, the recourse to expert scientists and healthcare providers, rather than politicians, has been often advised to address vaccine questions and concerns ^{[180] [181] [182]}. Similarly, religious leaders have been identified as key figures in the promotion of vaccines, as decisions on whether to have them are also determined by beliefs about religious acceptability (e.g. due to the fear that the vaccine might contain animal-derived ingredients)^{[183] [184]}. This is confirmed by comments in research conducted among attendees of two mosques in the city of Leeds in January 2021 highlighting the importance of faith-based approaches when it comes to trust^[185]. Finally, Community Champions have been indicated as trusted and influential voices capable of promoting schemes and initiatives within their community in a way that is responsive to specific local challenges^{[186] [187]}.

Similar suggestions to target vaccine hesitancy and the lack of confidence in the systems administering it, but that specifically pertain to Scotland, appear in a vaccination health inequalities impact assessment published by Public Health Scotland, recommending engagement and outreach work in collaboration with local services and reliance on trusted healthcare professionals to reduce barriers to uptake^[188]. A report published by GPs at the Deep End in April 2021, which summaries the discussion from a virtual roundtable with the Scottish Government, Public Health Scotland, health boards and third sector representatives, also stresses the potential benefit of relying on local leaders and using GP practices' knowledge of the local population to engage those still hesitant, thanks to embedded and trusted staff who have built rapport over time^[189]. Though work remains in facing the challenges illustrated in this sub-section, health boards have developed their own approaches in response to changing circumstances and new data, in order to better tailor their work to their local populations^[190]. Efforts have included co-production of communication messages together with community partners and faith leaders (for example, addressing concerns around Ramadan for those fearing the vaccine could invalidate the fast), delivery of vaccines at religious sites (e.g. churches and Mosques) and outreach work with certain communities, such as Gypsy/Travellers, the homeless and seasonal migrant workers^{[191] [192]}.