Does maternal immunity to SARS-CoV-2 protect against SARS-CoV-2 infection in infants under 12 months old in Scotland?

COVID-19 disease in children is generally less severe than in adults, most children with the COVID-19 virus (SARS-CoV-2) have mild or no symptoms. However, among children with SARS-CoV-2 infection, younger infants are at greatest risk of severe illness.

Current COVID-19 vaccines are not approved for use in children under 12 years old in the UK, and any future child vaccine programme would still not protect the very youngest infants. Maternal immunity to infection is important in protecting infants against infectious diseases, including tetanus, pertussis and influenza. Young babies can be protected by antibodies which pass from mother to baby through the placenta, or through breast-milk. In addition, if a mother is immune to a virus, she may be less likely to catch it and pass it on to her baby. We know that COVID-19 antibodies from mothers can be transferred to babies in the womb and in breast milk. We don't yet know how well those antibodies might protect infants against SARS-CoV-2 infection, or whether vaccinating mothers reduces the risk of infection in their babies. This added benefit would make vaccines more cost-effective, and might encourage more women to be vaccinated. As the pandemic continues, and the time between initial vaccination and pregnancy increases, this study might also help decide whether a booster vaccination in pregnant women would be useful. It would also help us predict how many infants might be infected over time as more mothers become immune.

We want to know how effective maternal COVID-19 vaccines are in protecting infants against SARS-Cov-2 infection, and whether maternal COVID-19 immunity, from either vaccination or prior infection, can reduce the risk to babies. To answer these questions we will undertake two studies.
The first study will include babies born in Scotland between 1st August 2021 and 31st July 2022. Using NHS surveillance data, we will identify which of these infants have laboratory-confirmed SARS-CoV-2 infection before their 1st birthday. Using birth, death, GP records and surveillance data, these infant "cases" will be matched to "controls", infants born within one week of the case, who did not have a positive SARS-CoV-2 test before their 1st birthday. We will then link these infants to maternal records, and use routinely collected NHS data, including maternity records, vaccination records, SARS-CoV-2 testing data, to compare the two groups. We aim to include all cases that year, matched to at least 4 controls. Our key objectives will be to compare the odds of maternal vaccination, or prior maternal COVID-19 infection, in infants with and without confirmed SARS-CoV-2 infection in the first year of life. We will also look at other factors which might change the risk of SARS-CoV-2 infection including gestation, maternal age, ethnicity, deprivation, and urban/rural location.

In the second study, we will identify cases and controls as above, but limited to infants born within NHS Greater Glasgow & Clyde healthboard. Using blood left over from maternal antenatal screening for infectious diseases, we will be able to measure maternal COVID-19 antibody levels druing early pregnancy. We will aim to collect samples from mothers of 500 cases and 1000 controls. We will then determine whether the presence of maternal COVID-19 antibodies (either from vaccine or natural infection) is associated with reduced risk of infection in their infants.

For both studies all patient-identifiable data will be managed within the NHS Safe Haven and use approved processes of pseudo-anonymisation to ensure patient data are kept private. Individual patients will not provide consent, but use of this data for public benefit will be approved by ethics and privacy committees.

These studies will help us understand how maternal COVID-19 immunity can help protect infants. This will help us plan vaccine programmes, and help inform vaccine choices for women in Scotland and elsewhere.

We will test the hypothesis that maternal SARS-CoV-2 immunity is associated with protection against SARS-CoV-2 infection in infants under 12 months old. We will undertake two case-control studies.
Study 1 will compare infants born in Scotland 1/8/21-31/7/22 with PCR-confirmed SARS-Cov-2 infection in the first year of life to infants without SARS-CoV-2 infection in the first year of life, matched 1:4 by date of birth, to determine:
a) the odds of maternal COVID-19 vaccination prior to delivery
b) the odds of maternal vaccination prior to pregnancy versus vaccination during pregnancy versus no vaccination
c) the odds of maternal SARS-CoV-2 infection prior to delivery
d) the odds of maternal SARS-CoV-2 infection prior to pregnancy, versus SARS-CoV-2 infection during pregnancy, versus no infection
e) the odds of maternal SARS-CoV-2 infection during the first year after delivery.
Study 2 will compare similar cases/controls, but limited to Greater Glasgow & Clyde and matched 1:2 by date of birth, to determine:
a) the odds of maternal SARS-CoV-2 IgG seropositivity during pregnancy
b) the odds of detectable SARS-CoV-2 neutralising antibodies during pregnancy
c) the odds associated with maternal SARS-CoV-2 IgG concentration.
Case/controls and linked maternal data will be identified from routinely collected NHS and national records data. Data on confounding factors will include infant sex, gestation, maternal age, ethnicity, and deprivation index. In study 2, excess blood from antenatal screening will be used to undertake SARS-CoV-2 IgG MSD-ECL assay and neutralisation assays.
Using conditional logistic regression, a multivariable model will be created to explore the interactions between maternal SARS-CoV-2 infection/immunity/COVID-19 vaccination, and other demographic/socio-economic predictors of infant SARS-CoV-2 infection. Data will be linked and pseudo-anonymised within NHS Safe Haven. Use of unconsented data will be approved by ethics/privacy committees.