Effectiveness of COVID-19 mRNA primary and booster vaccination against infection and hospitalisation during pregnancy: a target trial emulation and meta-analysis of data from 4 European countries

Objective To estimate vaccine effectiveness (VE) of COVID-19 mRNA vaccines administered during pregnancy. Primary (2-dose) vaccination was compared with unvaccinated women; and 1st booster (3rd dose) with primary (2-dose) vaccination. Design Target trial emulation cohort study. Setting Routinely collected health data from UK, Sweden, Spain, and Norway. All had complete vaccine exposure data and were mapped to the OMOP common data model. Participants Pregnant women (aged 12-55) with <=34 weeks of gestation, no history of COVID-19 in the 90 days prior and >=1 year of data visibility. Women were matched 1:1 to those with no dose and 2-dose vaccination, respectively, using weekly sequential matching from vaccination roll-out to 2023 (Swedish data: 2024). Main outcome measures The main outcomes were COVID-19 infection, hospitalisation and Intensive Care Unit (ICU) admission (COVID-related, excluding delivery-related care). Hazard ratios (HR) were estimated with Cox regression from 15 days post-vaccination, and VE was reported as 100 x (1-HR). Analyses were stratified by pregnancy trimester and vaccine brand. Database-specific results were pooled using a random-effects meta-analysis. Results We included 62,061 and 41,096 pregnant women at date of vaccination with a first and third dose, respectively. Median follow-up across databases ranged from 42 to 55 days for primary vaccination and 73 to 116 days for boosters. For primary vaccination, the meta-analysis showed a VE of 26.2% (16.2 to 35.1; I2 =0.7) against infection and 55.6% (44.1 to 64.8; I2 =0) against hospitalisation. For boosters, corresponding figures were 33.6% (-1.6 to 56.6; I2=1) and 34.1% (0.6 to 56.4; I2 =0.5). Event counts were insufficient to analyse VE against ICU admission. Results were consistent across pregnancy trimesters and vaccine brands. Conclusions Vaccination with a primary (2-dose) or a 1st booster (3rd dose) during pregnancy was effective in preventing COVID-19 hospitalisation, with modest and heterogeneous VE against infection across 4 European countries.