COVID-19 booster doses in pregnancy and global vaccine equity.

Immunisation against SARS-CoV-2 with mRNA vaccines remains the most effective way of preventing COVID-19-related morbidity and mortality. Medium-term data show that the efficacy of mRNA vaccination (two doses) is robust for up to 5–6 months, as supported by immunogenicity studies.1, 2 Thereafter, the effectiveness of mRNA vaccines diminishes, and booster doses have been recommended for various high-risk groups. In 2021, the American College of Obstetricians and Gynecologists recommended booster doses for pregnant and post-partum women on the basis of their increased risk of COVID-19-related complications. However, data on the durability of immune response in pregnant women are scarce.

Barda and colleagues reported the effectiveness of booster mRNA vaccines in a large population study from Israel. A booster dose administered at least 5 months after the second dose significantly reduced the rate of new COVID-19 infections, hospital admissions, and severe infections in a cohort of 1 158 269 individuals with a median follow-up time of 2 weeks. Based on these results, the number-needed-to-boost (NNB) to prevent one excess case of hospital admission was lower than the NNB to prevent severe COVID-19 (table ). However, for each of these outcomes, NNBs were about 20 times higher in those younger than 40 years, and 10–25 times higher in those without comorbidities, reflecting much lower absolute complication rates. Although these NNB estimates to prevent severe COVID-19 might be an overestimate for pregnant women, who have a two to three times increased risk of severe COVID-19 (compared with other women of reproductive age), even halving these NNBs based on age would mean that more than 10 000 booster doses would be required to prevent one case of hospitalisation or severe COVID-19 in pregnancy when administered 5 months after the second dose. The actual NNB to prevent hospitalisation or severe COVID-19 will be lower in the long term as the study had a median follow-up time of only 2 weeks. However, only in the presence of comorbidity would the NNBs be comparable to those for initial vaccination in pregnancy.

Table

Rate of breakthrough cases without boosters and number-needed-to-boost to prevent one case, by age and comorbidity

	Hospital admissions		Severe COVID-19
	Excess cases without boosters (per 100 000)	Number-needed-to-boost to prevent one case	Excess cases without boosters (per 100 000)	Number-needed-to-boost to prevent one case
By age, years
16–39	4·9	20 408	2·5	40 000
40–69	96·7	1034	54·4	1838
By comorbidity
Without existing comorbidities	11·9	8403	3·1	32 258
One to two comorbidities	101·9	981	78·8	1269

Given the current low vaccination coverage among pregnant women, efforts have rightly focused on increasing vaccine uptake in unvaccin-ated individuals. It remains to be seen whether campaigns to address vaccine hesitancy among pregnant women, or ensuring equitable access to vaccination more generally, are more important than the allocation of resources to the administration of booster doses. Although any individual can decide to maximise their protection via booster doses, regardless of previous risk status, it is important to convey the magnitude of expected absolute effect for informed decision making (table). Algorithms assessing the risk of severe COVID-19 in pregnant women can be useful for triaging the need for boosters, and for considering women who might be at even higher risk of COVID-19, such as those who might not have developed an adequate immune response to vaccination (eg, organ transplant recipients and those with acquired immune deficiencies), those who might be at increased risk of exposure to SARS-CoV-2 and other breakthrough infections (eg, health-care workers), or those who might be at high baseline risk for severe COVID-19 (eg, those with severe obesity or pregestational diabetes).

The global shortage of vaccines and unequal distribution of the available stock raises an important ethical dilemma for giving booster doses to any group. Unvaccinated pregnant women in low-income and middle-income countries are at much higher risk of dying from COVID-19 but are also less hesitant to receive vaccination. Furthermore, the absolute reduction in risk following a booster is likely to be small for most vaccinated pregnant women who do not have a comorbidity. Longitudinal profiling of immunogenicity induced by different types of vaccines in pregnant women is essential for informing booster timing. In the meantime, strategies for more equitable distribution of vaccines and reduction of vaccination hesitancy among the unvaccinated are likely to be more effective in reducing COVID-19 complications than offering boosters to all already-vaccinated pregnant women.