Vaccine effectiveness against mild and severe covid-19 in pregnant individuals and their infants in England: test negative case-control study.

Objective: To estimate real world vaccine effectiveness against symptomatic disease and hospital admission with the delta and omicron variants of the SARS-CoV-2 virus in pregnant individuals, and to estimate the protection conferred by previous infection and maternal vaccination in their infants. Design: Test negative case-control study. Setting: Community and hospital testing for covid-19, in England, 26 April 2021 to 9 January 2022 (delta variant period) and 29 November 2021 to 31 March 2022 (omicron variant period). Testing data were linked to Hospital Episode Statistics and Maternal Services Data Set (for data on pregnant individuals and infants), National Immunisation Management System (for covid-19 vaccinations), and Secondary Uses Service (for hospital admissions). Participants: 35 206 negative and 16 693 positive eligible test results in the delta variant period from pregnant individuals with symptoms of infection, aged 16-55 years, whose pregnancy ended in 2021, and 5974 negative and 4715 positive eligible test results in the omicron variant period. For infants born in 2021, 23 053 negative and 2924 positive eligible test results in the delta variant period and 13 908 negative and 5669 positive test results from infants in the omicron period. Main outcome measures: Vaccine effectiveness against symptomatic disease and hospital admission with the delta and omicron variants of the SARS-CoV-2 virus in pregnant women. Also, effectiveness of maternal vaccination and the protection conferred by previous infection in mothers in preventing symptomatic disease and hospital admission in their infants in the first six months of life. Symptomatic SARS-CoV-2 infection was confirmed by a positive polymerase chain reaction test result. Results: Vaccine effectiveness against symptomatic disease (delta and omicron infection) and against hospital admission (delta infection only) in pregnant individuals was high, as seen in the general population. A booster dose of vaccine gave sustained protection, with no evidence of waning up to 15 weeks after vaccination. Vaccine effectiveness against symptomatic disease peaked at 98.4% (95% confidence interval (CI) 88.4% to 99.8%) and 80.1% (73.8% to 84.9%) against the delta and omicron variants, respectively, after the booster dose of vaccine. Vaccine effectiveness after a two dose primary schedule against hospital admission with delta infection peaked at 92.7% (95% CI 79.9% to 97.4%) in pregnant individuals. Maternal vaccination during and after pregnancy also provided sustained protection from symptomatic disease and hospital admission after delta and omicron infection in infants aged up to six months, with the highest protection seen when maternal vaccination occurred during later pregnancy. The effectiveness of two maternal doses when the last dose was given in the third trimester was 86.5% (95% CI 81.9% to 90.0%) and 56.6% (46.7% to 64.6%) against symptomatic disease with delta and omicron infection, respectively, in infants, and effectiveness against hospital admission was 94.7% (78.2% to 98.7%) and 78.7% (58.2% to 89.1%), respectively. Previous infection with wild-type, alpha, and delta variants of the SARS-CoV-2 virus in pregnant individuals was more protective against mild and severe delta infection than omicron infection in their infants. Conclusions: The results of this study indicated that maternal vaccination prevented mild and severe disease in pregnant individuals and their infants for up to six months after birth. The findings support the promotion of both primary and booster vaccination for pregnant individuals to protect themselves and their infants.