Is it still suitable to depend on AstraZeneca for COVID-19 vaccine donations to developing countries?

The factors associated with hesitancy in receiving the COVID-19 vaccines have been widely examined by several studies worldwide. Although individual attitude plays a significant role in vaccine uptake, the WHO and public health experts believe that tackling the spread of COVID-19 is only achievable by guaranteeing vaccine equity across the globe, especially in low-and-middle-income countries, where the vaccination process is being hindered by other factors besides vaccine hesitancy. Among these factors is the refusal of the AstraZeneca vaccine because of its short shelf life. Therefore, we aimed in this letter to propose some solutions that may contribute to solving this specific problem.


Background
The COVID-19 pandemic started in China and was easily detected in less than a month in high-income countries (HICs) like the USA, Italy, Germany, and the UK. While the official reports say that lower income countries were infected later, there is no consensus about whether this was the actual case due to the lower diagnostic and surveillance capacity in low-and-middle-income countries (LMICs). But as the pandemic progressed, HICs started protecting their populations by funding corporations working on vaccines in exchange for early access to vaccinate their citizens 1 .
At the same time, other global efforts were trying to keep equity as the market will be swallowed by HICs. Therefore, the Independent Allocation of Vaccines Group (IAVG), which was established as a collaboration between the World Health Organization (WHO) and Gavi, set the goal of vaccinating 70% of the global population by mid-2022, partly with the help of the COVID-19 Vaccines Global Access (COVAX). This target was set to minimize the burden of the disease and the socio-economic effects of COVID-19 2,3 .
However, by the 22 June 2022, only 50 countries had met the target vaccination rate, the majority of which are HICs. Meanwhile, low-income countries still lack behind in vaccination coverage, having vaccinated only 10% of their population 4 . While HICs were offering booster doses in late 2021, 45 countries had vaccinated less than 10% of their population, and 105 had administered only the primary vaccination series to approximately 40% of their population. Moreover, many countries struggled to cover the vaccination needs of their elderly population 2,5 .

Factors affecting vaccine uptake in LMICs
Although it is evident that the number of COVID-19 cases is declining worldwide, new outbreaks are still being recorded around the world in various places 6 . Therefore, the race to vaccinate the whole world population is not near an end. Even with the COVAX contribution, which has so far shipped over a billion COVID-19 vaccines to 145 participants to cover at least 40% of a country's population vaccine needs 7-9 , LMICs are still struggling to combat the lack of vaccine supply. To date, only 17.1% of the African population received two doses of the vaccine 9 . The low vaccination rate caused by vaccine inequality (manifested by high uptake in more educated and richer people) in Africa may further facilitate the development of more variants, mimicking the appearance of the Omicron variant 10,11 .
Among the factors that prevented COVAX from donating the planned 8 billion vaccine doses to low-income countries are the delay of HICs to provide financial support and claiming a large amount of the manufactured vaccines 5 . Furthermore, a substantial part of the vaccines donated by HICs as a form of support to COVAX had a brief half-life, meaning that by the time of administration many doses had reached the expiry date 3 . What's more, COVAX supply to Africa only includes AstraZeneca, Sinopharm, BioNTech, Johnson & Johnson (J&J), and Moderna and has covered 59% of total doses received. And it was also decided that AstraZeneca, a cheap vaccine, is to be the main vaccine provided by COVAX 2,3 . Along with COVAX, Africa received its COVID-19 vaccination from Africa Vaccine Acquisition Task Team, BILATERAL, some specific HICs, and other unknown sources 12 .
More than a hundred nations have approved the use of AstraZeneca as part of their pandemic preparedness plans. However, various LMICs are currently rejecting or even destroying the AstraZeneca jabs sent to them. Unlike other COVID-19 vaccines that can be stored safely for up to 12 months, the shelf life of AstraZeneca is of only 6 months. This could constitute a problem when millions of jabs are delivered just before the expiry date 13 . This is, for example, the problem Nigeria faced last November when the government had to use near-expiry vaccines and dump around one million other jabs. Other West African countries were facing the same problem a few months after Nigeria 14 . Coupled with low vaccination rates, high vaccine hesitancy, and logistic challenges in African countries, vaccines with short shelf life are not appealing anymore 15 . And because a decrease in the demand for the vaccine (manifested by the decreased uptake) typically leads to a positive movement along the supply curve, a surplus in the number of vaccines available will occur. With time, many vaccines will expire; governments will be reluctant to purchase or request new doses, and international supporters of LMICs might think twice before sending more doses that may eventually expire. Subsequently, market equilibrium will be reached with the final decrease in supply.
Although the WHO is encouraging rich countries to donate more vaccines with longer expiry dates 16 , HICs continue to ship the vaccines that have a near-to-expiry date despite the possession of triple, quadruple, or quintuple the number of vaccines required by one country. And while developed countries were starting to administer booster doses, approximately three billion people worldwide were left unvaccinated, which only highlights vaccine inequity and nationalism. The WHO has long suggested delaying booster doses until the full vaccination (one dose of J&J or two doses of any other vaccine) was achieved in all countries. However, the emergence of the  23 , also started to refuse the one-dose J&J vaccine without a booster dose of an mRNA vaccine.

Proposed solutions
Accordingly, we propose the following actions: We believe that rich countries should consider providing poorer countries with the needed vaccines, focusing on Moderna and Pfizer when feasible.
In the case of the provision of AstraZeneca, newly manufactured vaccines should be sent to prevent their expiry before the time of administration. To properly achieve this, countries should consider estimating the actual number of needed vaccines for future booster doses and disregard storing doses that will unlikely be administered to their populations. Additionally, all HICs should accept, recognize, and approve the administration of vaccines produced by LMICs like Sinopharm, Sinovac, and Sputnik. Finally, AstraZeneca should consider testing the safety and efficacy of their vaccine beyond the declared "at least six months" shelf life 24 . The Food and Drug Administration of Thailand (Thai FDA) 25 and the Indonesian government 26 approved the increase of AstraZeneca's shelf life to nine months rather than only six based on the fact that extending shelf life will mostly not affect the safety of the vaccine, but it may lead to reduced potency, stability, and effectiveness (some protection is better than no protection) 25 . And just like the FDA has reviewed the potential for extending the shelf life of J&J and Pfizer vaccines 27,28 , further reviewing of the safety and effectiveness of the AstraZeneca vaccine after the six-month time point should be nudged.

Conclusion
Although the governments of HICs are to be partially blamed for some of the inequity in the COVID-19 vaccine distribution crisis in LMICs, governments of LMICs also have a duty toward the rapid distribution of the received vaccines as using nearto-expiry date vaccines can be lifesaving in many instances. But continued inequity and discrimination against LMICs will not help in lessening the frequency of viral mutation 29 as "no one is safe from COVID-19 until everyone is safe." 30

Declaration of funding
This paper was not funded.

Declaration of financial/other relationships
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. A reviewer on this manuscript has disclosed that they receive grant funding from Sanofi Pasteur and Merck Sharp and Dohme on unrelated investigator initiated grants. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions
VPT and AMM were principally responsible for formulating the study idea and design. All authors conducted the literature search and wrote and revised the manuscript. All authors approved the final version of the manuscript under the supervision of NTH.