Background
The pandemic is causing unprecedented impact on global health and the economy. In the absence of safe and highly effective vaccines and treatment options, non-pharmaceutical interventions are used to decrease transmission and reduce the burden of coronavirus disease 2019 (COVID-19) but most of these interventions have large economic costs [
1]. Effective vaccines against COVID-19 are urgently needed to reduce the significant burden of COVID-19 morbidity and mortality. Globally, there are over 274 vaccine candidates at various stages of development in the research pipeline. Of these, 59 candidates have entered clinical trials [
2].
On June 26, 2020, the World Health Organization (WHO) unveiled a plan to deliver 2 billion doses of COVID-19 vaccines, of which 50% will go to low- and middle-income countries, by the end of 2021 [
3]. Currently, the projected global production capacity is inadequate to provide COVID-19 vaccines for every human being on the planet, particularly immediately after the first vaccine has been licensed. It is possible that countries and entire regions will have no access to vaccines. For example, COVID-19 cases are rapidly increasing in most African countries [
4]. However, none of the COVID-19 vaccine candidates is being developed by an African manufacturer. Even if a vaccine were available, many low-income countries would have to rely on vaccines manufactured abroad. Hence national and multinational vaccine producers will need to allocate a proportion of their production to countries that do not have the financial ability to pre-order vaccine doses that are still to be licensed. Setting priorities for target populations to be vaccinated and optimizing resources within and between countries entails difficult choices. Nonetheless, this is critical for a successful global pandemic vaccination program, and this needs to be addressed urgently. The WHO Strategic Advisory Group of Experts on Immunization (SAGE) Values Framework for The Allocation and Prioritization of COVID-19 Vaccination offers core principles for vaccine distribution [
5]. These guidelines need to be further specified and tailored to each county, taking into local contexts including but not limited to the intensity of epidemic, the objectives of pandemic responses, the vaccine supply, and the size of the population eligible for vaccination.
China was the first country to face the COVID-19 pandemic, although only Wuhan, in Hubei Province, was hit by a major wave of infections [
6]. Nearly the entire population of mainland China (~ 1.4 billion people) is still susceptible to COVID-19. Recent surges of COVID-19 cases occurred in a growing number of cities such as Beijing, Dalian, Urumchi, and Kashgar, following one or more months without any report of locally acquired infections [
7]. There is a risk of a new major wave of COVID-19, especially after the economy and society have re-opened both domestically and abroad.
China has invested substantial resources in vaccines and is one of the main actors in the race to develop a vaccine to help control the COVID-19 pandemic, with resources provided by government, manufacturers, and non-governmental organizations [
8]. Eighteen vaccine candidates are being developed in mainland China; five of them are in phase III trials as of November 12, 2020 [
9]. New COVID-19 vaccine production facilities recently completed or currently under construction are expected to have the capacity to produce 0.61 billion doses by the end of 2020 and further expanded in 2021 [
10]. However, the output is far behind the quantity needed to vaccinate a population of nearly 1.4 billion people in mainland China alone (given a two-dose schedule for all vaccine candidates).
The Joint Prevention and Control Mechanism of the State Council roughly divides the target population for COVID-19 vaccination into three groups, including those with high risks of exposures to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), those with high-risks of severe outcomes, and the general population, with priority given to the former two groups [
10]. In July 2020, three COVID-19 vaccines were licensed in China for emergency use among individuals at high risk of exposure to SARS-CoV-2, including frontline medical personnel and overseas workers in China. Media reports show that over one million people have been vaccinated as of December 1, 2020 [
11,
12]. According to recent surveys [
13‐
15], the (general) Chinese population has a high level of willingness to accept COVID-19 vaccination. Hence, with more vaccines expected to be licensed by the end of 2020/early 2021, there is a need to define the priority target groups for a wide-scale COVID-19 vaccination program. This study aims to define the priority target populations, their size, and priority for a phased introduction of COVID-19 vaccination with evolving goals in mainland China, accounting for risk of severe illness and transmission. This approach is generalizable to inform national and regional strategies for the use of COVID-19 vaccines, especially in low- and middle-income countries.
Discussion
In the absence of specific antiviral treatment for COVID-19, vaccination likely represents the most promising way to control the COVID-19 pandemic. However, even if a COVID-19 vaccine becomes available, initial supplies will inevitably be limited. Supply issues could persist in the long term, due to huge global demand and limited production capacity. Almost everyone can potentially benefit from vaccination because of residual high susceptibility to SARS-CoV-2 infection. Considering different goals of a future vaccination program, changes in vaccine supplies, various levels of responsibility of population groups to the COVID-19 pandemic responses and essential services, as well as the risk of severe outcome and illness, we recommend a phased universal COVID-19 vaccination program for mainland China. Workers in critical sectors, including healthcare workers, law enforcement and security personnel, personnel in nursing home, and social welfare institutes, as well as sectors of energy, water, food, and transportation, and overseas workers/students (49.7 million) are the main candidates to receive high priority for vaccination, in order to maintain essential societal functions. Subsequently, we propose to extend the vaccination program to older adults, pregnant women, and those with underlying medical conditions (563.6 million), in order to reduce severe outcomes of COVID-19. Finally, working-age adults, school-age children, and younger children (784.8 million) could be vaccinated in order to reduce symptomatic COVID-19 infections, and/or to stop SARS-CoV-2 transmission.
Target population groups are further grouped into vaccination tiers from 1 to 6, with Tier 1 having the highest priority. Even though individuals within a tier have equal priority for vaccination, it may be necessary to sub-prioritize vaccination of groups within a tier if initial vaccine supplies are severely limited. For instance, cold-chain workers who have been particularly affected by COVID-19 and are often linked to workplace transmission could thus be vaccinated before other personnel within Tier 2 [
70]. Other examples are represented by individuals aged ≥ 80 years or older with underlying conditions, who may be vaccinated before other personnel within Tier 3 or by individuals of < 60 years of age with ≥ 2 underlying conditions who may represent a sub-prioritized category within their Tier [
20]. Further studies are warranted to examine the sub-prioritization within each vaccination tier. Although other factors like smoking, being male, and being an ethnic minority were found to be risk factors of severe outcome and deaths from COVID-19 in previous studies [
71‐
73], they were not accounted for when determining priority population here due to consideration of equity and feasibility of vaccination.
The Joint Committee on Vaccination and Immunisation (JCVI) in the UK largely prioritizes individuals for vaccination based on age, considering simple age-based programs to be easier to implement and thus have a higher chance of achieving a high vaccine uptake [
74]. As of December 1, 2020, JCVI does not provide precise advice on the prioritization for frontline healthcare and social workers. On the other hand, the Framework for Equitable Allocation of COVID-19 Vaccine of the National Academy of Sciences, Engineering, and Medicine suggests that in the US priority should be given to frontline healthcare workers, and those having significant risk of severe illness or death from COVID-19 (as individuals with two or more underlying health conditions) [
20]. Compared to the UK and the US, the epidemiological situation in China is quite different, with an almost entirely susceptible population to SARS-CoV-2 infection and very limited local transmission. In this context, the frontline workers and individuals studying/working abroad represent the categories at higher risk of infections in mainland China. Our advice on priority populations for a COVID-19 vaccination came under the umbrella of the WHO SAGE Values Framework for The Allocation and Prioritization of COVID-19 Vaccination [
5], and took into consideration the local context and the possible goals of a COVID-19 vaccination program in China.
The majority of the current COVID-19 vaccine candidates are being trialed as two-dose schedules [
9]. A total of 70 million, 789 million, and 1099 million doses are separately needed to cover 70% of individuals in critical infrastructure sectors, persons at high risk of severe outcomes of COVID-19, and persons at high risk of acquiring symptomatic illness/infections. Between 2007 and 2015, the volume of all vaccines supplied (
n = 55) licensed in mainland China varied from 666 million doses to 1.19 billion doses per year [
75]. Several manufacturers state that a total of 0.61 billion doses of COVID-19 vaccine could be produced this year and 2.1 billion doses in 2021 [
10]. Even if these candidate vaccines could be licensed and manufactured smoothly, it will take 7 months to vaccinate 70% of the general population. This is assuming an optimistic vaccine delivery rate that is over twofold higher than the maximum rate at which H1N1pdm vaccines were delivered in 2009 (3 million doses administered each day). Such a large-scale vaccination program like COVID-19 could also represent a major challenge for current the National Immunization Program in China, which is currently focused on childhood vaccination rather than on adult vaccination. The limited production capacity will likely further delay COVID-19 vaccination programs. This dilemma is likely not unique to China, and other countries across the world, particularly in low- and middle-income regions, will face a similar challenge.
Although according to survey results [
13‐
15], 72.5–91.3% of the Chinese population aged 18 years or above appear to be willing to accept a COVID-19 vaccine, specific groups like pregnant women may be less willing to get COVID-19 vaccine due to safety concerns. These factors may delay or reduce the effective vaccine coverage. The acceptance of COVID-19 vaccination in specific segments of the population merit further studies.
Identifying individuals with underlying conditions is critical for a risk-based vaccination campaign. In China, the National Basic Public Health Service Program provides all residents with electronic health records, which have information on underlying conditions and can be queried by community healthcare centers [
76]. Electronic health records as well as other medical records may be used to identify high-risk individuals with underlying conditions.
Our study has a number of limitations. First, we have qualitatively discussed the segments of the population to be prioritized in a COVID-19 vaccination program as well as the rationale behind prioritization choices. However, we could not quantitatively examine whether prioritizing older adults to reduce severe outcomes is a better choice than prioritizing working-age adults or school-age children to reduce illness/transmission. Mathematical modeling is urgently needed to assess both the health and economic impacts of potential vaccination strategies, and the potential to reduce for herd immunity benefits. Second, we did not consider eligibility for vaccination due to lack of efficacy and/or safety concerns that may affect specific groups such as older adults, people with pre-existing medical conditions, pregnant women, and very young children, since no vaccine has been licensed yet. Third, we did not consider real-time reactive outbreak immunization strategies because it is impossible to estimate the corresponding target population size. However, we strongly recommend use of COVID-19 vaccination during local outbreaks coupled with other non-pharmaceutical interventions in order to prevent subsequent waves of disease. Moreover, we did not discuss prioritization based on geography; the risk of COVID-19 exposure may be low in regions that have seen widespread COVID-19 activity by the time the vaccine is available and have a high level of population immunity. This may not be particularly relevant for China where the epidemic has been well controlled, but it may affect vaccine prioritization in other regions.
Because of the high burden and limited capacity for vaccine production, we have highlighted that more attention should be paid to low- and middle-income countries. The WHO SAGE Values Framework for The Allocation and Prioritization of COVID-19 Vaccination offers guidance for allocating and targeting COVID-19 pandemic vaccines, by providing six core principles and twelve objectives that further specify the six principles [
5]. We tailored it to China-specific contexts accounting for the risk of illness and transmission, lessons learned from the response to the COVID-19 outbreak in Wuhan, the objectives of COVID-19 pandemic responses, and experience gained from the 2009 H1N1 pandemic vaccination program in China, in addition to the risk of severe outcomes, symptomatic illness, and transmission. Our recommendations for mainland China could be used as a template for usage of such guidelines. When a vaccine becomes available, our recommendations need to be reassessed to consider the eligibility of population subgroups based on the licensure label. They also need to be further reassessed periodically to account for changes in vaccine supply, demand, and local epidemiology. Although we propose a general framework to define vaccination priorities, the proposed vaccination program needs to be tailored locally, accounting for country-specific contexts such the objectives of the pandemic responses, the local level of transmission, the make-up of first responders, and essential workers as well as the capacity of immunization services.
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