Prioritizing Pregnant Women for Coronavirus Disease 2019 Vaccination in African Countries

Abstract

Coronavirus disease 2019 (COVID-19) in pregnancy is associated with excess maternal and infant morbidity and mortality in both African and higher-resource settings. Furthermore, mounting evidence demonstrates the safety and efficacy of COVID-19 vaccination for pregnant women and infants. However, national guidelines in many African countries are equivocal or lack recommendations on COVID-19 vaccine in pregnancy. We summarize key data on COVID-19 epidemiology and vaccination among pregnant African women to highlight major barriers to vaccination and recommend 4 interventions. First, policymakers should prioritize pregnant women for COVID-19 vaccination, with a target of 100% coverage. Second, empirically supported public health campaigns should be sustainably implemented to inform and support pregnant women and their healthcare providers in overcoming vaccine hesitancy. Third, COVID-19 vaccination for pregnant women should be expanded to include antenatal care, obstetrics/gynecology, and targeted mass vaccination campaigns. Fourth, national monitoring and evaluation of COVID-19 vaccine uptake, safety, surveillance, and prospective outcomes assessment should be conducted.

Evidence from African and non-African settings indicates that COVID-19 in pregnancy is associated with excess maternal and infant morbidity and mortality. We recommend universal COVID-19 vaccination for pregnant African women, as available data on safety and efficacy in pregnancy are reassuring.

Early data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy, largely derived from the Global North, indicated that coronavirus disease 2019 (COVID-19) significantly increased the risk of poor maternal and infant outcomes [1–5]. More recently, a multi-national prospective cohort study of the effects of COVID-19 in pregnancy and neonatal period (INTERCOVID) (including Ghana, Nigeria, and 16 countries outside Africa) found that SARS-CoV-2 infection among pregnant women was associated with higher rates of intensive care unit (ICU) admission, preeclampsia, eclampsia, cesarean delivery, and maternal mortality compared to those in pregnant women without infection. Furthermore, considering birth outcomes, pregnant women with SARS-CoV-2-infection had higher rates of preterm birth and stillbirth [6].

Following the INTERCOVID study findings, data on COVID-19 and pregnancy have become available from more African countries. The African Forum for Research and Education in Health (AFREhealth) Research Collaboration on COVID-19 and Pregnancy conducted a retrospective cohort study across 22 health facilities in 6 African countries [7]. Among SARS-CoV-2–infected women, being pregnant was associated with a 2.4 times higher risk of ICU admission and about a 2 times higher risk of mortality. Furthermore, SARS-CoV-2–infected (vs uninfected) pregnant women had a 5 times greater hazard of in-hospital death. These data highlight the potentially devastating consequences of COVID-19 in pregnant women and demonstrate the importance of preventive measures for both maternal and infant health [7].

SAFETY AND EFFICACY OF COVID-19 VACCINE IN PREGNANT WOMEN

Although pregnancy was an exclusion criterion in the earliest trials of COVID-19 vaccine and treatment candidates [8,9], more recent trials have enrolled pregnant women [10,11]. Initial studies provided preliminary evidence for the safety, immunogenicity, and effectiveness of messenger RNA (mRNA) vaccines in pregnant women [12,13] and reported no adverse effects of vaccination related to pregnancy or neonatal outcomes [14–16]. A systematic review by Girardi et al found that COVID-19 vaccination in pregnant and lactating individuals is immunogenic, safe with respect to vaccine-related adverse events and obstetrical and neonatal outcomes, and effective in preventing COVID-19 disease [17]. In a recent population-based study from Sweden and Norway, among pregnant women, vaccination against SARS-CoV-2 compared with no vaccination was not significantly associated with an increased risk of adverse pregnancy outcomes [18]. The majority of COVID-19 vaccines used in this study were mRNA vaccines; however, 2% of vaccinees received the Oxford-AstraZeneca adenovirus vector vaccine, and most were vaccinated during the second and third trimesters. Albeit limited, published data on the safety of adenovirus vector vaccines (Oxford/AstraZeneca ChAdOx1nCoV-19 and Johnson & Johnson/Janssen JNJ-7836735 vaccines) and the inactivated virus CoronaVac vaccine are also reassuring [19–21]. Continued postapproval monitoring of vaccine safety in pregnancy for all available COVID-19 vaccines should remain a priority.

Additionally, maternal vaccination studies have shown efficient postvaccination transfer of maternal SARS-CoV-2 antibodies across the placenta and into breastmilk, suggesting a degree of protection for breastfeeding neonates and infants [22–25]. In the United States, maternal completion of a 2-dose primary mRNA vaccine series during pregnancy was associated with a 61% decrease in COVID-19–related hospitalization among infants aged <6 months [26]. Furthermore, COVID-19 vaccine is safe and poses no additional risk to breastfeeding women or breastfed infants [27,28]. SARS-CoV-2–specific immunoglobulin G and immunoglobulin A antibodies have been shown to be present in breastmilk following vaccination of breastfeeding women, which could provide protection of infants should they be exposed to infection [29,30]. Therefore, the potential benefits of maternal vaccination while breastfeeding appears to greatly outweigh the risks [27].

While future COVID-19 vaccine trials should strongly consider increasing the inclusion of pregnant women and monitor their outcomes, current evidence suggests that these vaccines are safe and protective for both women and infants.

BARRIERS TO COVID-19 VACCINATION AMONG PREGANT WOMEN IN SUB-SAHARAN AFRICA

There are notable geographic variations in COVID-19 vaccination recommendations for pregnant women. According to the COVID-19 Maternal Immunization Tracker (https://www.comitglobal.org/), Australia and most countries in North America, Europe, South America, and South and Southeast Asia are now recommending COVID-19 vaccination for some or all pregnant women. By contrast, as of 23 February 2022, only 10 of 54 African countries are recommending COVID-19 vaccines for some or all pregnant women [31]. These findings mirror larger global patterns of vaccine inequity, with failure of national vaccine recommendations to consistently include pregnancy. These policy gaps, along with other factors such as misinformation, negatively affect uptake of COVID-19 vaccination in pregnancy [32]. As of 23 February 2022, full primary series COVID-19 vaccine coverage in general populations across Africa was just 12%, with rates in two-thirds (67%) of countries <20% [33]. Clearly, the World Health Organization (WHO) target of 70% vaccine coverage by June 2022 will not be attained in most African countries [34]. Data on COVID-19 vaccine coverage in pregnancy are scarcely available, even in African countries with permissive policy recommendations [35]. Although policies regarding COVID-19 vaccine use in pregnancy have evolved over time, imbalances in recommendations between jurisdictions exacerbate prevailing inequities in access and use of COVID-19 vaccines [36].

Vaccine hesitancy may pose an additional barrier to preventing COVID-19 and its consequences in women and infants. In a meta-analysis of 12 studies totaling >16 000 people, only 47% (95% confidence interval [CI], 38%–57%) of pregnant women planned to receive the COVID-19 vaccine [37]. Notably, the lowest intent was seen in Africa at 19% (95% CI, 17%–21%). Prior uptake of other vaccines (influenza and/or tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis [TdaP]) during pregnancy was associated with higher intent to receive the COVID-19 vaccine (odds ratio, 3.03 [95% CI, 1.37–6.73]; P = .006) [38]. The most common reasons for COVID-19 vaccine hesitancy and low vaccine uptake in pregnancy include misinformation and disinformation disseminated on social media and other platforms, which mislead the public about maternal side effects (eg, infertility), presumed lack of safety data among pregnant women, and inaccuracies about the potential for fetal harm [39–41]. It is critical to evaluate and implement evidence-based educational and counseling interventions that address misinformation and disinformation to reassure pregnant women and their families and increase their confidence in proven effectiveness and safety of COVID-19 vaccines.

PROPOSED FACILITATORS FOR AND SOLUTIONS TO ENSURE PROMOTION, UPTAKE, AND EQUITY OF COVID-19 VACCINATION IN PREGNANCY IN AFRICAN COUNTRIES

The strong evidence of potentially severe effects of SARS-CoV-2 infection on pregnant women and infant outcomes supports the prioritization and scale-up of maternal COVID-19 vaccination. Given the adverse consequences of COVID-19 during pregnancy and the increasing data supporting a favorable safety profile of the Pfizer-BioNTech BNT162b2 vaccine in pregnancy, WHO recommends the use of COVID-19 vaccines for pregnant women in its updated 2022 recommendations [42,43]. The recommendations put emphasis on informing pregnant women that they can receive the vaccine and providing them with information about the increased risks of COVID-19 in pregnancy and the likely benefits of vaccination, in line with strong recommendations from other international societies [44,45]. There is evidence to show that vaccination is beneficial even for individuals with a history of SARS-CoV-2 infection; that postinfection maternal SARS-CoV-2 humoral immunity wanes rapidly during pregnancy, resulting in low or absent protective antibody titers for a significant proportion of pregnant women (depending on time of infection); and that a single boosting dose of BNT162b2 mRNA vaccine induced a robust increase in protective antibody titers for both mother and newborn [46]. Additionally, for immunization programs to succeed, target populations must have confidence in the benefits and safety of the vaccines. Fear of vaccines may be pronounced among pregnant women and their healthcare providers, and effective communications are needed for both [47,48]. For example, the American College of Obstetricians and Gynecologists has developed tools to assist obstetricians in discussing COVID-19 vaccination with their pregnant patients [50]. Finally, potential facilitators of COVID-19 vaccination in pregnant women in low- and middle-income countries include access to the wide network of community-based antenatal care clinics where routine maternal vaccines are administered, such as hepatitis B, and TdaP or tetanus toxoid. To help close the vaccination gap in pregnant African women, we recommend the following actions. First, policymakers and programs should prioritize pregnant women for COVID-19 vaccination and accelerate scale-up and 100% coverage. Second, empirically supported public health campaigns should be sustainably implemented to inform and support pregnant women and their healthcare providers in overcoming vaccine hesitancy [44]. Third, COVID-19 vaccination availability should be expanded to include antenatal care, obstetrics/gynecology, and community clinics where other vaccines (eg, tetanus) are routinely administered to pregnant women (Table 1). Alternative approaches such as mass campaigns including mobile clinics should be considered. Although the mRNA vaccines require cold-chain storage, innovative solutions can be identified, such as use of highly insulated and reusable containers that can maintain temperatures at −80°C for up to a week in the field even if the container is opened several times a day, as was done for Ebola virus vaccines [49]. Finally, it is critically important to collect, monitor, and evaluate COVID-19 vaccine uptake and safety in pregnant women (eg, in national registries), while continuing national SARS-CoV-2 infection surveillance and implementation of prospective cohort studies to accurately assess outcomes while minimizing bias.

Table 1.

Barriers and Solutions to Ensure Promotion and Equity of Coronavirus Disease 2019 Vaccination Among Pregnant Women in Sub-Saharan Africa

Area of Focus	Barriers	Solutions/Recommendations
Policymaking	Many national guidelines in African countries are equivocal or lack recommendations on COVID-19 vaccination among pregnant women	Urgent update of national guidelines in African countries for stronger recommendation of COVID-19 vaccination for pregnant and lactating women based on currently available efficacy and safety data
Vaccination communication and education	Low acceptance of COVID-19 vaccination among pregnant women and women of childbearing age COVID-19 vaccine misinformation and disinformation disseminated on social media and other platforms	Evidence-based, locally tailored COVID-19 vaccine promotional campaigns to target pregnant women and their families, dispelling misinformation and extolling the benefits of vaccination for both mothers and infants COVID-19 vaccine promotional campaigns also targeting healthcare workers providing for pregnant women [48]
Healthcare systems delivery	Heterogeneity of Pfizer and Moderna mRNA COVID-19 vaccine supply in African countries and their requirement for ultra-cold storage of −80°C and −20°C (−112°F and −4°F, respectively) Low COVID-19 vaccine access for young women and women in rural and other underserved communities with very poor health infrastructure	Innovative solutions for cold chain, including use of high-tech insulated and reusable containers that can maintain temperatures of −80°C for up to a week in the field [50] Need for additional safety data on use of non-mRNA COVID-19 vaccines with less cold-chain storage needs (eg, viral vector or inactivated vaccines) for pregnant women Integration of COVID-19 vaccination into routine pregnancy-related vaccination (eg, tetanus) and expansion of vaccine administration points to include antenatal care and obstetrics/gynecology clinics as well as community clinics and centers to increase access/uptake for pregnant women and those of childbearing age Mass campaigns for COVID-19 vaccination to include mobile clinics targeting pregnant women
Monitoring and evaluation	Lack of national COVID-19 uptake, coverage, and safety data for pregnant women to support policy and practice	Create national registries for vaccination in pregnancy Track COVID-19 vaccination uptake in pregnant women Conduct routine surveillance and prospective cohort studies of SARS-CoV-2 infection and outcomes in pregnant women

Abbreviations: COVID-19, coronavirus disease 2019; mRNA, messenger RNA; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

CONCLUSIONS

Accumulating evidence from African and non-African settings indicates that SARS-CoV-2 infection during pregnancy is associated with more severe COVID-19 disease and poorer maternal and infant outcomes. Studies also show that mRNA COVID-19 vaccines are safe and effective for use in pregnancy, but more data are warranted for other non-mRNA vaccines. Policymakers and public health institutions in African countries should prioritize pregnant women in COVID-19 vaccine programs and work to accelerate scale-up and move toward 100% coverage through evidence-based policy, tailored community messaging, and education of professional and traditional providers caring for pregnant women.

Notes

Author contributions. J. B. N., N. A. S.-A., and M. J. S. conceptualized and drafted the manuscript. All coauthors provided substantial contributions in terms of critical revision of the draft and reviewed as well as approved the final version submitted for publication.

Acknowledgments. The authors thank and appreciate the efforts of all personnel across Africa who are contributing to the prevention and treatment of COVID-19 among pregnant women and other populations at risk.

Financial support. This work was supported by the US National Institutes of Health (NIH)/Fogarty International Center (FIC) (grant number 1R25TW011217-01 to the African Forum for Research and Education in Health; Prinicipal Investigators: Prisca Adejumo, Jean B. Nachega, Nelson K. Sewankambo, Fatima Suleman) (payment to the University of Ibadan, Ibadan, Nigeria-PA; Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, South Africa-JBN; Makerere University, Kampala, Uganda-NKS; University of Kwazulu Natal, Durban, South Africa-FS).

Potential conflicts of interest. J. B. N. reports grants from NIH/FIC paid to her institution and unrelated to this work (grant numbers 1R25TW011217-01, 1R21TW011706-01, and 1D43TW010937-01A1). N. S. A. reports grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, unrelated to this work and paid to institution (grant number R01HD089866) and an NIH/FIC award through the Adolescent HIV Prevention and Treatment Implementation Science Alliance for the Central and West Africa Implementation Science Alliance. P. J. R. reports grants or contracts unrelated to this work and paid to institution (grant numbers 5R01AI075045-12, 5R01AI139179-04, and 5R01AI117001-07). A. Z. reports grants or contracts unrelated to this work and paid to institution: Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET, https://www.pandoraid.net/) funded by the European and Developing Countries Clinical Trials Partnership and the European Union Horizon 2020 Framework Program for Research and Innovation. J. W. M. reports research grants unrelated to this work and paid to the University of Pittsburgh from the NIH to the Pitt-Ohio State Clinical Trials Unit (grant number UM1 AI068636), the University of Pittsburgh Virology Support Laboratory (grant number UM1 AI106701), the I4C Martin Delaney Collaboratory for an HIV Cure (grant number UM1 AI126603), the REACH Martin Delaney Collaboratory for HIV Cure (grant number UM1 AI164565), and the National Cancer Institute through Leidos (contract numbers HHSN261200800001E and 75N91019D00024), US Agency for International Development, Gilead Sciences, and Janssen Pharmaceuticals; consulting fees from Gilead Sciences (scientific advisory board), Accelevir Diagnostics (consulting agreement), and Merck (consulting agreement); shares from Abound Bio, and share options with Co-Crystal Pharma and Infectious Diseases Connect; a consulting agreement with Xi-an Yufan Biotechnologies; and employment with the University of Pittsburgh. M. J. S. reports grants unrelated to this work and paid to institution (Massachusetts General Hospital): NIH/National Institute on Aging (grant number R01AG059504-03) and NIH/National Heart, Lung, and Blood Institute (R01 HL141053-04). L. M. M. reports consulting fees from the World Health Organization as a consultant on COVID-19 in pregnancy and mother-to-child SARS-CoV-2 transmission (this contract is now completed) and payment from Virology Education for a continuing education talk on SARS-CoV-2 in pregnancy and possibility of mother-to-child SARS-CoV-2 transmission. All other authors report no potential conflicts.

All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.