key: cord-0869665-wikz6kzk
authors: Noushad, Mohammed; Al-Awar, Mohammed Sadeg; Al-Saqqaf, Inas Shakeeb; Nassani, Mohammad Zakaria; Alrubaiee, Gamil Ghaleb; Rastam, Samer
title: Lack of access to COVID-19 vaccines could be a greater threat than vaccine hesitancy in low-income and conflict nations: the case of Yemen
date: 2022-02-02
journal: Clin Infect Dis
DOI: 10.1093/cid/ciac088
sha: aeecb210a8389a4ce193f098c8f232e7399113fd
doc_id: 869665
cord_uid: wikz6kzk

BACKGROUND: Vaccine hesitancy and vaccine inequity are two major hurdles towards achieving population immunity to COVID-19. Although several studies have been published on vaccine hesitancy among numerous populations, there is inadequate information on any potential correlation between vaccine acceptance and lack of access to vaccines. Our cross-sectional study in a low-income country aimed to fill this gap. METHODS: We conducted a nation-wide cross-sectional survey among the general population in Yemen, a low-income conflict country. Participants from all the provinces in Yemen were included in the study. We evaluated factors influencing agreement to accept a COVID-19 vaccine and any potential correlation between vaccine hesitancy and lack of access to vaccines. RESULTS: Overall, 50.1% of the 5329 respondents agreed to accept a COVID-19 vaccine. Only 39.9% of the participants agreed to having access to a COVID-19 vaccine, with females indicating lower access than males. Potential determinants of vaccine acceptance included being male, updating self on the development of vaccines against COVID-19, opinion about severity of COVID-19, anxiety about contracting COVID-19, concerns about the safety of COVID-19 vaccines and lack of access to vaccines. CONCLUSIONS: our results indicate that the immediate threat in Yemen towards achieving population immunity is the severe shortage and lack of access to vaccines, rather than vaccine hesitancy.

The SARS-CoV-2 virus that causes coronavirus disease-19 (COVID-19) has been responsible for millions of deaths worldwide and a huge socio-economic burden. The introduction of effective vaccines and implementation of robust immunization campaigns worldwide has led to a global decline in morbidity and mortality from COVID-19. 1 However, in order to achieve the threshold immunization coverage necessary to attain population immunity, policymakers will need to address two concerns: the phenomenon of "vaccine hesitancy", the reluctance or refusal to vaccinate despite the availability of vaccines, and equitable global vaccine distribution. 2 Early studies on vaccine acceptance among the adult population have suggested acceptance rates ranging from as low as 23.6% in Kuwait to as high as 97% in Ecuador. 3 A more recent systematic review also showed wide variations in COVID-19 vaccine acceptance rates, ranging from 15.37% in Cameroon to 98.06% in China. 4 Apart from geographic variations, global hesitancy to vaccines has also been shown to be time dependent, with hesitancy rates ranging from 21% in April 2020, increasing to 36% in July 2020 and later declining to 16% in October 2020. 5 Current statistics suggest that, as of 4 December 2021, more than 44% of the world"s population have been fully vaccinated against COVID-19. 6 Although it seems like a great achievement, a country-wise break-up of the numbers indicate that at least 68% of those fully vaccinated are from high-income countries (HIC), while those in low-income countries (LIC) account for a grim 3.1%, a result of largescale vaccine inequity. 6 This extreme discrepancy could have serious implications for global population immunity, as it could allow the virus to mutate into newer variants. This has been proven by the recent discovery of the "Omicron" variant in South Africa (where only about 24% of the population has been fully vaccinated against , in addition to the eight variants that have A c c e p t e d M a n u s c r i p t 4 been already identified until early November 2021, causing renewed worry among health experts and policymakers. [7] [8] Apart from LICs, vaccine inequity could be particularly crippling in conflict countries that are already facing difficulties associated with logistic constraints and the near collapse of their healthcare systems. 9 Since Yemen started its vaccination campaign in mid-April 2021, as of 4 December 2021, it has received less than a million COVID-19 vaccine doses through the COVAX, for a population of more than 30 million. 10 Currently, only about 1.2% of the Yemeni population has been fully vaccinated against COVID-19, while the neighboring countries of Oman and Saudi Arabia have fully vaccinated more than 54% and 63% of their populations respectively. 6 The huge discrepancy in access to vaccines could be a greater threat than vaccine hesitancy in LICS and conflict countries and could even be a cause for vaccine hesitancy. 11 Currently there is inadequate information on the determinants of vaccine hesitancy in conflict countries and any potential correlation between vaccine hesitancy and lack of access to vaccines. Our nation-wide cross-sectional exploratory study aimed to identify determinants of vaccine acceptance and any correlation between access to COVID-19 vaccines and its acceptance in Yemen, a low-income conflict country.

A cross-sectional self-administered survey was conducted among the adult general population in Yemen between 4 and 28 October 2021. The "Report of the SAGE working group on vaccine hesitancy" was used as a guide in preparing the questionnaire. 11 As part of the validation of the study, a pilot study was initially carried out on 10 participants, after which expert opinions were taken from specialists in the field. The bilingual (English and Arabic) survey questionnaire developed on Google A c c e p t e d M a n u s c r i p t 5 Forms required less than 5 min to complete. Participation was voluntary and the participants provided informed consent on the survey platform before proceeding to the survey items. The participants" anonymity was guaranteed during the data collection process. The survey form was designed in such a way that only complete forms would qualify for submission. This study was approved by the Research Committee of College of Dentistry, Dar Al Uloom University, Riyadh, Saudi Arabia (COD/IRB/2020/2).

Sample size was calculated using Open Source Epidemiologic Statistics for Public Health-OpenEpi (http://www.openepi.com/Menu/OE_Menu.htm, accessed on 25 October 2021). We use 50% as the hypothesized % frequency of outcome factor in the population, which is recommended for unknown frequency, and 2% as absolute precision. The result was a sample size of 4130 to get 99% confidence interval. We added 20% to overcome the possibilities of receiving missing data. Our final sample size was 4,956, which was our target for the current study.

Participants were invited to complete the questionnaire through the Whatsapp platform. This was done by forming a group of carefully selected students and faculty of Al Razi University, Sana"a, Yemen hailing from different parts of Yemen to share the questionnaire in their Whatsapp groups. However, due to the high population concentration in the Azal region (due to massive population displacement from other parts of Yemen to Sana"a) and it being the point of distribution of the questionnaire, maximum participation was expected from this region. Participants below the age of 18 years were not included in the study. General attitudes towards vaccines were measured using a set of 2 items. First, participants were asked if vaccines were really necessary to overcome the pandemic. Participants were asked if they thought vaccine manufactures followed recommended development and production guidelines.

Responses were rated on a five-point Likert scale from 1 "strongly agree" to 5 "strongly disagree".

Participants" attitudes towards the health authorities were measured using a set of 4 items. Participants were asked if they were happy with the health authorities" handling of the pandemic, and their management of vaccination campaigns. Participants were then asked if they were happy with the NGOs and the international community in helping Yemen vaccinate its population. Responses were rated on a five-point Likert scale from 1 "strongly agree" to 5 "strongly disagree". Participants were then asked if they had access to COVID-19 vaccines. Responses were rated on a five-point Likert scale from 1 "strongly agree" to 5 "strongly disagree".

This was measured using a set of 7 items. First, participants were asked if vaccines should be made mandatory and if the participant intended to be vaccinated against COVID-19. Further questions included concern for others who would be in greater need for the vaccine, intention to protect others with weaker immunity, fear of possible side effects of the vaccine and if the participant would take the vaccine only if it was free of cost. Responses were rated on a five-point Likert scale from 1 "strongly agree" to 5 "strongly disagree".

A c c e p t e d M a n u s c r i p t 7

Socio-demographic factors included age group, sex, nationality, region, and employment.

Participants" reports on chronic medical conditions (e.g., asthma, diabetes, hypertension, heart disease, and/or cancer) were used to indicate the presence or absence of pre-existing co-morbidity. Other variables included participants" self-updating on COVID-19 vaccine development, prior infection with COVID-19, perception of COVID-19 severity, compliance with government COVID-19 guidelines, and anxiety towards contracting COVID-19.

Descriptive statistics were expressed as percentages and numbers for each item/survey question. The main outcome of this study was the intention to vaccinate. The current study considered any participant to have an intention to vaccinate if he/she agreed or strongly agreed on the item "I will get vaccinated with the Covid-19 vaccine", or if they had already taken the vaccine. Bivariate statistical analysis of the relationship between the main outcome "intention to vaccinate" and predictors was performed using the Chi-squared test for trend for ordinal factors, and the Chi-squared test for categorical variables. A multivariate binary logistic regression model was used to determine the predictors for intention to vaccinate. The following factors were examined as potential predictors for intention to vaccinate: age group, sex, nationality, presence of any medical condition, following 

Overall, 5329 out of the 8220 invited adult subjects completed the survey questionnaire (response rate 64.83%). Of the participants, 50.1% expressed their agreement to get vaccinated against COVID-19.

Characteristics and demographics of the participants are shown in Table 1 . Data regarding participants" awareness about COVID-19 are presented in Table 2 . It can be noted that only 15.6% took the COVID-19 vaccine.

Concern about the side effects of vaccines was apparent among a high proportion of the participants (66.4%). Less than half of the participants (47.2%) were happy with the health authorities" management of the pandemic and the vaccination campaigns. Similarly, just a little more than a half of the participants expressed their satisfaction with the support provided by non-governmental organizations (NGO) (57.3%) and the international community (53.9%). Unfortunately, only 39.9% of the participants agreed that they have access to a COVID-19 vaccine. The abovementioned results are summarized in Table 3 .

The bivariate statistical analysis indicated an association between participants" intention to vaccinate and 10 factors (p < 0.05) (Table 4 ). Interestingly, access to COVID-19 vaccine was associated with a high intention to vaccinate.

The logistic regression analysis indicated six determinants of agreement to get vaccinated against COVID-19 among the study population. These include being male, those following the updates about COVID-19 vaccines, those who believed COVID-19 to be a severe disease, those with greater anxiety about contracting COVID-19, those concerned about the side effects of COVID-19 vaccines and those who have access to a COVID-19 vaccine (p < 0.05) ( Table 5) .

A c c e p t e d M a n u s c r i p t 9

The current study looked for the determinants of COVID-19 vaccine acceptance and its potential correlation with access to vaccines, in a low-income country devastated by a seven-year-long conflict.

Our findings in Yemen indicate a COVID-19 vaccine acceptance rate (50.1%) comparable to that of a similar study we conducted in neighboring Saudi Arabia (56.2%), a high-income country. 12 The acceptance rate is also significantly higher than that of a large study conducted among Arabs, in which only one in eight respondents reported their willingness to accept a vaccine. 13 A survey conducted during the first two weeks of the COVID-19 outbreak in Yemen in April 2020 reported a higher vaccine acceptance rate of 61%. This however was only if the vaccine was offered free of cost.

The acceptance rate was however shown to decrease to 43% if they were required to pay for it. 14 Studies in neighboring conflict countries have indicated varying results. For example, a study in Somalia indicated a higher acceptance rate of 76.8%, whereas two studies in Syria indicated lower acceptance rates of 37% and 36%. [15] [16] [17] Not much is known about the SARS-CoV-2 transmission trajectory in Yemen. However, considering the difficulties in imposing preventive measures like lockdowns, social distancing, etc., the total case count of 10,025 infections and 1954 deaths (as of 6 December 2021) as indicated in the World Health Organization (WHO) dashboard is a huge underestimation. 9 This is evident from the results of a study in Aden governorate conducted during November -December 2020, which indicated a seroprevalence of 27.4%. 18 Nonetheless, the agreement of at least 63% of the participants on COVID- A c c e p t e d M a n u s c r i p t 10 Apart from demographic factors, our results indicate determinants of vaccine acceptance, similar to studies in other low as well as high-income countries. [15] [16] 19 These include opinion on the severity of COVID-19, anxiety of contracting COVID-19, concerns on the side-effects from COVID-19 vaccines, etc. (Table 5 ). The logical finding that individuals who perceive COVID-19 to be a severe disease and are anxious about contracting it being more likely to accept a vaccine have been reported in other Arab and conflict countries like Syria. A study in four Middle Eastern countries, including Iraq, also indicated similar results. 20 Although fear of side effects of COVID-19 vaccines has been shown to be dropping globally, it is still a cause for concern as demonstrated in several studies. 21 A large multi-country study among Arabs concluded that one of the most cited reason for rejecting COVID-19 vaccines is concerns about their side effects. 13 Similar findings were reported in two studies in Syria. [16] [17] These results highlight the responsibility of policymakers in addressing the critical issue of educating the public on the safety of vaccines.

Trust in authorities and policies have been shown to have a positive impact on vaccine acceptance. 22 A large multi-country study on more than 36,000 Arab participants revealed that one of the most cited reasons for not agreeing to accept a COVID-19 vaccine was distrust in healthcare policies. 13 Shifting front lines, sudden flare-ups in violence, attacks on aid workers, non-unified governing systems, administrative and movement restrictions, etc. could compromise the work of humanitarian agencies and NGOs in conflict settings. 23 Unfortunately, trust in NGOs and the international community was low among the participants in our study. The extreme inequity and delay in vaccine supply in Yemen, coupled with the lack of transparency could be one of the reasons for this mistrust. Further studies will shed more light on this.

The strongest determinant of vaccine acceptance in our study was access to vaccines, meaning, an increase in supply could lead to an increase in demand/acceptance. Only 39.9% of the participants in our study definitely agreed that they have access to a COVID-19 vaccine. Unfortunately, due to the extreme shortage in vaccine supply, even after almost a year since the approval of A c c e p t e d M a n u s c r i p t 11 vaccines by regulatory bodies, less than 2% of the Yemeni population is fully vaccinated against COVID-19, while most of the high-income countries have fully vaccinated almost 70% of their populations. 6 The current campaign of administering booster doses in high income-countries at the expense of limiting access to the recommended two doses in low-income countries has only compounded this challenge. 24 Policymakers should consider limiting booster doses to the vulnerable so that the excess doses can be diverted to low-income countries. But this seems highly unlikely.

Apart from vaccine inequity, residents of conflict nations, especially women and children, are faced with the additional challenge of difficulty in accessing vaccination facilities. For example, a study in 2018 revealed that nearly 30.6% of the Yemeni population lived more than 30-min travel time from the nearest fully or partially functional public primary health-care facility, and more than 42.4% lived more than 1 h from the nearest fully or partially functional public hospital, assuming access to motorised transport. 23 Additionally, access to vaccination and healthcare facilities can also be severely compromised during flare-ups of the conflict. As expected, results of our study indicated that females had significantly lower access to COVID-19 vaccines than males. This highlights the need for NGOs like the WHO, MSF, UNICEF, etc. to coordinate with the Yemeni authorities to ensure that vaccination campaigns are conducted in locations that provide safe and convenient access to both males and females alike. One feasible solution would be to provide single dose vaccines to residents of areas with compromised access to vaccination facilities.

In conclusion, our results suggest that the immediate threat in Yemen towards achieving population immunity is the severe shortage and lack of access to vaccines, rather than vaccine hesitancy. Under the current circumstances, a possible solution to accelerate vaccine coverage in Yemen could be to increase distribution of single dose vaccines (Yemen has already received 151,000 doses of the J&J/Janssen single dose vaccine through the COVAX facility) and those that do not require critical storage conditions. 10 The first step towards achieving sufficient vaccination coverage in Yemen A c c e p t e d M a n u s c r i p t 12 remains ensuring adequate supply of vaccines to meet the demand. The WHO, other NGOs operating in Yemen, the COVAX and donor nations should work determinedly and inclusively with all parties in Yemen to ensure that no one is left behind in the pursuit to achieve optimum vaccine coverage.

Although Azal province has been overrepresented partly due to the greater population concentration there, the fact that our study could cover respondents spanning over all the provinces of Yemen, representing different demographic characteristics, and the large sample size are notable strengths.

Moreover, this is the first study on vaccine acceptance in Yemen following vaccine rollout, and the first study examining any potential correlation between vaccine acceptance and lack of access to vaccines. The major limitation of our study is the mode of the study. Since we used a web-based selfadministration mode of survey, there could be potential bias among the participants in responding to the survey questions. Moreover, since participants in our study included only those with access to internet facilities, there is a possibility that they represent those with higher socio-economic status and greater and easier access to healthcare and vaccination facilities. This could be another potential source of bias. However, due to the restrictions related to the pandemic and the conflict, the web based questionnaire distribution was the best mode currently available. Future studies with wider penetration, especially covering rural and underserved areas in Yemen will provide further information on the attitudes of Yemenis towards vaccines against COVID-19.

Our results in Yemen, a low-income conflict country suggests vaccine acceptance comparable to those of neighboring countries. The potential correlation between vaccine acceptance and access to vaccines however indicates that a potential increase in supply could lead to an increase in demand. Data Availability Statement. The questionnaire used in the current study is not publicly available due to certain restrictions. However, it is available from the corresponding author (Mohammed Noushad) on reasonable request. Financial support. We sought no funding to support this work. M a n u s c r i p t 18 M a n u s c r i p t 19 

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7%) (45.1%-53.6%) (57.1%-65.2%) Work Unemployed Employed

4%-43.5%) (61%-64.8%) Compliance with COVID-19 preventive guidelines Good Moderate Poor 62

A c c e p t e d M a n u s c r i p t M a n u s c r i p t 20 A c c e p t e d M a n u s c r i p t 22