FormalPara Key Summary Points

A comprehensive review of COVID-19 vaccine recommendations from countries in Latin America, Asia, and Africa and the Middle East.

Vaccine distribution during the COVID-19 pandemic has been challenging due to production shortages, economic constraints, and supply-chain infrastructure limitations, which severely hindered low- and middle-income countries.

A variety of vaccination strategies were applied in different regions of the world.

High primary COVID-19 vaccination rates for adults across regions studied were observed.

Coverage for primary series in children, as well as for booster doses in adolescents and adults, were low across the countries studied at the time of writing.

Introduction

Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide [1, 2]. Although the number of deaths and hospitalizations due to recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection peaks have notably decreased relative to peaks earlier in the pandemic in 2020 and 2021, before vaccines were rolled out broadly, current weekly numbers of infections, hospitalizations, and deaths, as well as long-term effects of COVID-19, continue to threaten public health across the Americas, Southeast Asia, and Africa and the Middle East [3]. The continued emergence of new variants of concern have compounded challenges for mounting adequate public health responses. For instance, since January 2022, the highly transmissible SARS-CoV-2 Omicron variant has been predominant, and by mid-August 2022, BA.4 and BA.5, two sub-lineages of the Omicron clade (B1.1.529), became the predominant subvariants globally [4].

For the first time since the start of the pandemic, the supply of COVID-19 vaccines to low- and lower-middle-income countries seems no longer a binding constraint, although there are critical distribution and delivery bottlenecks in some countries [5]. In addition, in some countries, an insufficient number of trained and remunerated health and care workers has been highlighted as a common challenge to the delivery of COVID-19 tools [5]. Other regional issues within low- and lower-middle-income countries and regions have imposed challenges in the pandemic public health response, including varied and dynamic sociopolitical environments, geography, and existing disease priorities [6]. In Latin America and Asia, the COVID-19 pandemic has exposed the preexisting inequities [7, 8]. In the Middle East, the effects of COVID-19 have varied widely across the region: the ability to respond to the pandemic has been inadequate, with chronic conflicts and divisions weakening healthcare systems and leading to less effective regional cooperation [9].

The aim of this narrative review was to summarize the evolving COVID-19 vaccination recommendations in countries in Latin America, Asia, and Africa and the Middle East across vaccine platforms, age groups, and special subpopulations, such as the immunocompromised. Primary and booster vaccination, as well as heterologous booster regimens, are discussed. We also examine the preliminary impact of such diverse vaccination strategies in these regions, including key vaccine effectiveness data in the era of Omicron variants.

Methods

COVID-19 vaccination recommendations, the vaccines in use, and coverage in various age groups were gathered from multiple diverse sources, such as official country dashboards for COVID-19, vaccine technical committee websites and publications, and documentation from relevant health ministries of each region. Countries were selected on the basis of the availability and clarity of vaccine recommendations at the time of writing, and if confirmation was available from the government or other official sources that the strategy was in place. Countries were included from three regions: Latin America (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Panama, Peru, and Uruguay), Asia (India, Indonesia, Malaysia, the Philippines, Singapore, and Thailand), and Africa and the Middle East (Bahrain, Kuwait, Lebanon, Morocco, Qatar, Saudi Arabia, South Africa, and the United Arab Emirates). In addition, we conducted a literature search on 6 August 2022 in PubMed for studies on vaccine effectiveness using “SARS-CoV-2 vaccine” and “effectiveness” as keywords alongside each country included in this review. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

The Diversity of COVID-19 Vaccine Programs

Worldwide, COVID-19 vaccine recommendations have evolved, with vaccine availability and the increased understanding of vaccine safety, real-world effectiveness, SARS-CoV-2 variant prevalence, collective population immunity, and waning protection over time since vaccination or infection. Tables 1, 2, 3, 4, 5, and 6 present COVID-19 vaccine recommendations for adults, adolescents, and children in the Latin American, Asian, and African and Middle Eastern countries included in this review, respectively, as of August 2022. Information on vaccine type and corresponding platform are summarized in Table 7 and Fig. 1. Information on the number of each type of vaccine administered in each region as of 14 September 2022 is summarized in Fig. 2.

Table 1 General COVID-19 vaccine recommendations in Latin America by country: adults
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Table 2 General COVID-19 vaccine recommendations in Latin America by country: adolescents and children
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Table 3 General COVID-19 vaccine recommendations in Asia by country: adults
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Table 4 General COVID-19 vaccine recommendations in Asia by country: adolescents and children
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Table 5 General COVID-19 vaccine recommendations in Africa and the Middle East by country: adults
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Table 6 General COVID-19 vaccine recommendations in Africa and the Middle East by country: adolescents and children
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Table 7 List of approved vaccines in the countries included in the reviewa
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Fig. 1
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COVID-19 vaccination recommendations. Data at the time of writing are presented by region for the countries included in the review

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Fig. 2
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Type of COVID-19 vaccines used and the number of doses (millions) administered to date in each region. Data show the cumulative number of doses administered according to vaccine manufacturer (current as of 14 September 2022 [11]). Data for Latin America include Chile, Peru, Ecuador, Argentina, and Uruguay; data for Africa and the Middle East include South Africa only; data for Asia include Nepal only. mRNA vaccines include BNT162b2 and mRNA-1273, and other vaccines include BBIBP-CorV, Ad5-nCoV, Gam-COVID-Vac, and NVX-CoV2373

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COVID-19 Vaccine Programs in the General Adult Population

At the time of writing, use of multiple vaccine platforms in adults (defined as ≥ 18 years of age in most countries) is a frequent practice in all regions surveyed (Fig. 1). Across the included Latin American countries, mRNA, replication-deficient adenoviral vector, and inactivated virus vaccines are largely recommended for the primary series in adults (Table 1). In the included Asian countries, in addition to the above-mentioned platforms, protein subunit vaccines are available for adults in most countries, including India (Table 3). A similar trend is observed in Africa and the Middle East for the included countries except for Qatar, where only mRNA vaccines are recommended (Table 5).

In the countries included in this review, for the 2-dose primary series, mix-and-match regimens (i.e., heterologous prime-boost vaccine types [10]) were usually not recommended in Latin America (with the exception of Argentina and Chile) or Asia (with the exception of the Philippines, Thailand, and Indonesia). Mix-and-match regimens were generally allowed in Africa and the Middle East (Fig. 1).

For booster doses given after a 2-dose primary series, several of the countries studied in each region implemented a heterologous booster regimen. Although mRNA vaccines are the preferred vaccine platform recommended across all studied countries, an exclusive use of mRNA vaccine boosters was observed only in Lebanon, Qatar, and Saudi Arabia in the Middle East and Uruguay in Latin America, while other countries studied also used other vaccine platforms according to vaccine availability. Figure 3 provides an overview of booster vaccination recommendations by region and country at the time of writing. In included Latin American countries (apart from Argentina and Chile, in which a second booster is recommended in those ≥ 18 years of age), a second booster was available for adults > 40 years old approximately 4 months after dose 3. In the included Asian countries, a second booster was recommended only in elderly adults (generally ≥ 60 years of age) and in those ≥ 18 years old with certain comorbid conditions (e.g., immunocompromised conditions) except in Malaysia where this age cutoff was ≥ 12 years. Across all studied countries in Africa and the Middle East, second booster doses were recommended only in Bahrain, Saudi Arabia, Lebanon, and South Africa (Fig. 3).

Fig. 3
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Booster dose use: 3- and 4-dose recommendations by region. Data at the time of writing are presented by region for the countries included in the review. UAE United Arab Emirates

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COVID-19 Vaccine Programs in Children and Adolescents

Both mRNA and inactivated virus vaccines were approved by regulatory bodies for pediatric age groups in the majority of the studied countries as of August 2022. In adolescents (defined in the majority of countries as those ≥ 12–17 years old), generally only mRNA vaccines were recommended in the included countries; inactivated vaccines were also authorized and recommended in Brazil, Chile, Indonesia, Thailand, Bahrain, Morocco, and the United Arab Emirates (Tables 2, 4, 6). In the included countries, a booster dose in adolescents was implemented only in the Philippines, Singapore, and Thailand in Asia, and only in Qatar, Bahrain, and South Africa in Africa and the Middle East. However, most countries in Latin America had already implemented a booster dose in this age group as of August 2022.

Regarding the pediatric population under 12 years of age, while mRNA vaccines are available for children from 6 months of age and inactivated virus vaccines were available for children from 3 years of age, the majority of studied countries in Asia and Africa and the Middle East recommended only mRNA vaccines in children (Tables 4, 6). In Latin America, mRNA and inactivated virus vaccines were recommended in Argentina, Brazil, Chile, and Peru, while only inactivated virus vaccines were recommended in Colombia and Ecuador (Table 2). In most countries reviewed across all regions, a booster dose was not recommended for children ≥ 5–11 years of age at the time of writing.

Vaccination Coverage

Vaccination against COVID-19 began in the USA on 14 December 2020. Of the countries included in this review, Argentina, Bahrain, Chile, Singapore, and Mexico started vaccinations at the end of December 2020, while other countries started vaccinating in January or February 2021 [11]. At the time of this writing, vaccination rates from 2-dose primary series and booster vaccinations varied widely across countries and regions studied (Table 8).

Table 8 Vaccination coverage in the countries included in the review
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Lessons Learned from Primary and Booster Implementation

Real-world evidence has been crucial during the COVID-19 pandemic to inform critical vaccination decisions [12]. Real-world vaccine effectiveness data have been published for many of the countries examined in this review. These data are critical as they not only support findings from clinical trials but also enable evidence-based decisions in the implementation of vaccination programs.

Real-World Effectiveness from the Primary Vaccination Series

Real-world data from primary vaccination series in Latin America, Asia, and Africa and the Middle East generally showed high short-term effectiveness across vaccine platforms. However, after emergence of SARS-CoV-2 variants, showing increased immune evasion and higher transmissibility, evidence of significant waning of vaccine effectiveness, particularly against infection and mild disease, was observed, but with more sustained protection against severe outcomes of disease [13]. In Brazil, from February–July 2021, the Brazilian National Immunization Program reported vaccine effectiveness against death ≥ 14 days after primary vaccine series for each of the vaccines in use. Completion of primary vaccination was associated with 98% effectiveness (among 20–30-year-olds) for replication-deficient adenoviral vector vaccine ChAdOx1-S, 90% (among 40–59-year-olds) for mRNA vaccine BNT162b2, and 83% for inactivated virus vaccine CoronaVac [14]. When effectiveness was estimated according to age group, this study found a sharp declining trend after two doses of CoronaVac in the elderly, particularly among those older than 80 years, where protection against death was as low as 45% compared with 71% among the age group of 60–79 years or 83% for the age group of 40–59 years. In a mass vaccination campaign in Chile, vaccine effectiveness of CoronaVac against hospitalization, intensive care unit (ICU) admission, and death was > 80% and vaccine effectiveness of BNT162b2 against hospitalization and ICU admission was approximately 95% [15, 16]. In Argentina, the risk of all-cause death after a 2-dose primary vaccination series was reduced by 97%, with no significant differences between replication-deficient adenoviral vector vaccine Sputnik V and ChAdOx1-S [17]. In Colombia, BNT162b2, ChAdOx1 nCoV-19, Ad26.COV2.S (replication-deficient adenoviral vector vaccine), and CoronaVac vaccines were all effective in preventing COVID-19–associated hospitalization and deaths in fully vaccinated adults ≥ 60 years old, with BNT162b2 and ChAdOx1-S showing the highest effectiveness against hospitalization (83–91%) and death (88–98%) [18]. In Uruguay, vaccination with BNT162b2 reduced deaths by 94% in individuals ≥ 80 years old, while CoronaVac reduced deaths by 95% in 18–49-year-olds [19].

Real-world data from Asia also confirm short-term effectiveness of primary vaccination series. In India, the effectiveness of ChAdOx1-S against infection in fully vaccinated individuals was 89% [20]. Another study among healthcare workers predominantly vaccinated with ChAdOx1-S (> 97%), vaccines were 57% effective against moderate-to-severe disease [21]. In Malaysia, BNT162b2, ChAdOx1-S, and CoronaVac were all highly effective at preventing ICU admission (72–96%) or death (82–95%) in ≥ 18-year-olds [22]. Another Malaysian study reported that age-standardized mortality rates per 100,000 population were 43 times higher in unvaccinated individuals than in those fully vaccinated with BNT162b2, and 13 times higher than in those who received inactivated virus vaccines [23]. In adolescents in Malaysia, BNT162b2 was 66% effective in preventing SARS-COV-2 infections [24].

In Bahrain, four COVID-19 vaccines (Sinopharm, Sputnik V, ChAdOx1-S, and BNT162b2) were rolled out; all were protective against infection, hospitalization, and ICU admission versus unvaccinated individuals, but recipients of the Sinopharm vaccine were at higher risk compared with the other vaccines [25]. In Saudi Arabia, COVID-19 case numbers and COVID-19–associated deaths were significantly reduced after introducing BNT162b2 and ChAdOx1-S vaccines [26]. Other studies in Saudi Arabia reported reduced risk of hospitalization or death for those vaccinated with BNT162b2 or ChAdOx1-S vaccines versus unvaccinated individuals [27, 28]. In Qatar, vaccination with both mRNA vaccines were highly protective against COVID-19–related hospitalization or death [29].

Effectiveness of Booster Vaccinations

Given evidence of waning vaccine efficacy after the 2-dose primary series [30,31,32], it is important to study the effectiveness of subsequent booster doses. A Brazilian study including more than 14 million individuals, in the context of Gamma and Delta being the dominant viral variants, found that vaccine effectiveness 6 months after the two-dose primary regimen of CoronaVac against both SARS-CoV-2 infection and COVID-19–related severe outcomes waned for all age groups, particularly in the elderly. A BNT162b2 booster 6 months after the second dose of CoronaVac improved vaccine effectiveness against infection to 92.7% (95% CI 91.0–94.0) and vaccine effectiveness against severe outcomes to 97.3% (95% CI 96.1–98.1) 14–30 days after the booster [33]. In Chile, a study of homologous and heterologous booster strategies found effectiveness against hospitalization was 86% for three doses of CoronaVac and 96% with a CoronaVac primary series and a BNT162b2 booster [34]. In Argentina in October 2021, a press release reported that a single dose of Sputnik Light vaccine was an effective booster for other vaccine platforms [35].

Booster doses of mRNA vaccines BNT162b2 or mRNA-1273 were effective in Singaporean adults, with 73% protection against confirmed infection and 95% protection against severe infection compared with individuals who had no booster [36]. Heterologous boosting with mRNA-1273 after a BNT162b2 primary series conferred greater protection than three BNT162b2 doses (82% versus 73%) [36]. Among South African healthcare workers, a homologous booster of Ad26.COV.2 was up to 85% effective against hospitalization [37].

Vaccine Effectiveness against the Omicron Variant

In November 2021, the SARS-CoV-2 variant B.1.1.529 (Omicron) was designated a variant of concern by the World Health Organization [38] and rapidly became predominant globally [4]. Omicron is more transmissible than earlier variants of concern and with greater antibody escape [39]; thus, it is important to examine vaccine effectiveness data in the Omicron era. The SARS-CoV-2 Omicron variant (B.1.1.529 or BA.1) has since been replaced by successive emerging lineages BA.2, followed by BA.4 and BA.5. Since the emergence of the Omicron variant and its subvariants, vaccine effectiveness data confirm that protection against disease from current vaccines is lower than for previous variants [38,39,40,41]. Importantly, vaccination remains associated with higher levels of protection against the severe outcomes due to Omicron [41]. With Omicron BA.5 now predominant [4], it is likely that contemporary data of effectiveness against this subvariant will be available shortly. A recent Brazilian study examined vaccine effectiveness during a period of Omicron predominance against symptomatic COVID-19 and severe COVID-19 (hospital admission or deaths) for a CoronaVac primary series and homologous (CoronaVac) and heterologous (BNT162b2) booster doses [42]. Vaccine effectiveness 8–59 days after a homologous booster with inactivated vaccine was 9% against symptomatic COVID-19 and 74% against severe COVID-19; a BNT162b2 mRNA booster gave additional protection, with vaccine effectiveness of 57% and 86% against symptomatic and severe COVID-19, respectively [42]. In Chile, effectiveness of CoronaVac in a 2-dose primary series in children found modest protection against symptomatic infection with the Omicron variant (38%), but higher protection against severe disease (approximately 65%) [43].

In Singapore, two primary doses of BNT162b2 in adolescents was 25% and 75% effective against Omicron-associated infection and hospitalization, respectively, while a booster dose achieved effectiveness of 56% against infection and 94% against hospitalization compared with unvaccinated individuals [44]. Similarly, a study in children 5–11 years old in Singapore during the Omicron wave reported effectiveness of BNT162b2 of 37% against reported infection and 83% against hospitalization [45].

In South African healthcare workers, vaccine effectiveness of BNT162b2 was 71–88% against Omicron-associated hospitalization from 13 days to 4 months after the second dose; two doses of Ad26.COV2.S were similarly effective [40]. In another South African study, BNT162b2 effectiveness against hospitalization was estimated to be 70% during the Omicron period versus 93% in the period when Delta was predominant [46]. Another South African study found that a third dose of BNT162b2 was 66% and 69% effective against Omicron BA.1/BA.2- and BA.4/BA.5-associated hospitalization, respectively, between 1 and 2 months after the third dose, although effectiveness waned 3 to 4 months after the third dose to 50% and 47%, respectively [47]. In Qatar, two doses of mRNA-1273 or BNT162b2 had comparable, moderate, and short-lived protection against symptomatic Omicron infection (43–48% in the first 3 months after dose 2) but were highly protective against Omicron-associated severe disease or death (70–80% at any time after dose 2) [48]. In the same study, a booster dose of BNT162b2 was > 90% effective against severe, critical, or fatal COVID-19 [48]. In Qatar, BNT162b2 booster effectiveness against symptomatic Omicron infection was 49% and 77% against COVID-19–related hospitalization and death due to Omicron infection versus the primary series [49]. The same study reported booster effectiveness of mRNA-1273 against symptomatic Omicron infection versus the primary series of 47%, but the effectiveness of mRNA-1273 against COVID-19–related hospitalization and death could not be calculated [49]. Another study from Qatar investigated the effectiveness of vaccination with BNT162b2 or mRNA-1273, immunity from previous infection with a variant other than Omicron, and hybrid immunity (previous infection plus vaccination) against symptomatic Omicron infection [50]. The effectiveness of three BNT162b2 doses was 52%, while the effectiveness of previous infection plus two or three doses of BNT162b2 was 55% and 77%, respectively [50]. All types of immunity had strong protection (> 70%) against severe COVID-19 or COVID-19–related hospitalization or death [50].

Implications for Future Vaccination Policies

Vaccination remains the key strategy to protect against COVID-19, help curb the pandemic, and maintain protection from new SARS-CoV-2 variants [51]. It is estimated that nearly 20 million lives were saved through vaccination during the first year of COVID-19 vaccine rollouts [52].

At the early stages of the pandemic, limited access, production shortages, economic constraints, and even political and public health neglect could have contributed to the variety of vaccination strategies deployed in the studied regions [53,54,55]. Compared with the USA or most European Union countries, which established their vaccination strategy only on the basis of mRNA and viral vector vaccines from four main brands [11], many of the countries studied in this review used three or more different vaccine platforms in their mass vaccination programs, chosen from more than ten brands. This diversity brings substantial complexity to vaccine implementation, considering the differences in cold chain, handling, and storage particularities and the potential impact on cost, healthcare provider training, vaccination uptake, and even in vaccine confidence [56]. Despite all challenges, vaccination coverage in adults for the primary schedule was generally high among the countries studied.

Although the supply of COVID-19 vaccines to low- and lower-middle-income countries now appears less constrained compared with earlier in the pandemic [57], booster uptake seems a challenge in most of the countries studied. Efforts to prioritize booster vaccinations in adults and high-risk groups [58], together with limited local capability to maintain mass-vaccination infrastructure [56], could potentially explain the suboptimal implementation of COVID-19 vaccines for younger age groups, particularly those younger than 12 years. Robust evidence coming from the regions studied could provide additional support for earlier policy preference of using an mRNA vaccine as a booster because of the safety profile and higher effectiveness against severe outcomes, especially during the Omicron circulation period [40, 42, 46, 47, 49, 50, 59, 60].

While North American countries and some European countries are already planning a programmatic use of COVID-19 vaccines, which includes bivalent booster (formulations containing the spike protein sequences from both the ancestral Wuhan strain and an Omicron variant) implementation in the autumn of 2022 [61, 62], a sustainable approach in the pandemic-to-endemic period is still not clear in most of the studied countries. Despite a substantial decrease in the number of severe COVID-19 cases and associated deaths, uncertainties remain regarding the trajectory of SARS-CoV-2 and the clinical impact of future variants [63]. Vaccination against COVID-19, including among children and adolescents, is likely the primary strategy to end the pandemic [64,65,66]. Countries and regions need strategies in place to overcome vaccine inequity, fatigue, hesitancy, and misinformation [63], as well as ensuring access and supply.

A limitation of this review is that not all countries from each region are included due to the data available at the time of writing. Additionally, the rapidly evolving nature of the COVID-19 pandemic means that vaccination data and vaccine recommendations will have changed since the time of this writing. A strength of this article, however, is that this is the first review to gather comprehensive vaccine recommendations from countries in Latin America, Asia, and Africa and the Middle East, regions that are mostly represented by low- and lower middle-income countries. There is still an important gap in COVID-19 vaccine implementation in some countries; future vaccination strategies should consider the lessons learned in these regions.