Does maternal immunity to SARS-CoV-2 protect against SARS-CoV-2 infection in infants under 12 months old in Scotland?
Lead Research Organisation:
University of Glasgow
Department Name: MRC Centre for Virus Research
Abstract
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.
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.
Technical Summary
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.
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.
Publications
Goulding A
(2023)
Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study.
in Archives of disease in childhood. Fetal and neonatal edition
Ho A
(2023)
Adeno-associated virus 2 infection in children with non-A-E hepatitis.
in Nature
| Description | MRC University of Glasgow Centre for Virus Research Clinical Academic Research Partnership |
| Organisation | University of Glasgow |
| Department | MRC - University of Glasgow Centre for Virus Research |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My award is a Clinical Academic Research Partnership which established a collaboration between myself (a Consultant Paediatrician working for NHS Greater Glasgow and Clyde) and the MRC University of Glasgow Centre for Virus Research (CVR). In 2021 I proposed the original research idea for the funded project, which examines the association between maternal SARS-CoV-2 immunity, and infants' risk of SARS-CoV-2 infection in the first year of life. I developed the research proposal and have spent the first year of the award establishing robust data collection processes and securing required ethical and public benefit and privacy panel approvals. In addition to the specific project outcomes, the aim of this partnership was to develop closer links between clinical and academic institutions in Glasgow. The benefit of this was demonstrated in the investigation of an outbreak of unexplained hepatitis in children in Glasgow in 2022, where I was able to provide clinical expertise to inform and support the research approach, and contribute to clinical data collection and analysis to link to the virology findings. |
| Collaborator Contribution | My partners at the CVR, Dr Antonia Ho and Professor Brian Willett, have provided mentorship and advice in developing the maternal-infant SARS-CoV-2 research proposal and support through the process of obtaining required approvals. In the 2022 outbreak of unexplained hepatitis Dr Ho co-ordinated the research approach to the investigation, bringing in other colleagues at the CVR and collaborating with NHS, Public Health, and research groups across the UK to complete the work. This very effective collaborative effort identified a likely cause of the outbreak - co-infection of adeno-associated virus 2 (a virus previously not thought to be pathogenic) with adenovirus or other viruses. We also identified a common HLA type in the majority of children affected, which has previously been associated with auto-immune disease and may represent a genetic vulnerability. The final results were published in Nature in early 2023. |
| Impact | The maternal immunity-infant SARS-CoV-2 project is in the early stages so has not produced direct outcomes this year. The results of the unexplained hepatitis research investigation are published here: https://doi.org/10.1038/s41586-023-05948-2 This collaboration involved research virology, clinical input from myself (paediatric infectious diseases), paediatric gastroenterology colleagues and clinical virology, and public health teams across the UK. |
| Start Year | 2022 |
| Description | Public Health Scotland |
| Organisation | Public Health Scotland |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | My Clinical Academic Partnership award and project on maternal immunity and infant SARS-CoV-2 infection has helped established new collaboration with colleagues at Public Health Scotland (PHS). The project makes use of population wide routinely collected clinical data. In the last year I have worked with the Electronic Data Research and Innovation service (eDRIS) team at PHS to develop data collection processes and gain required approvals for my project to proceed. My project idea expands on previous work by Prof. Rachael Wood and her team in the Covid in Pregnancy (COP) Study. I proposed and developed a new research question that will add scientific benefit to the data already collected by the previous study. This collaboration led Prof Wood to invite me to contribute my clinical expertise to analysis and interpretation of data on neonatal SARS-CoV-2 infection from the COP study. As previously described, I also worked closely with Public Health Scotland in the investigation of the unexplained hepatitis outbreak in 2022. |
| Collaborator Contribution | The eDRIS team are responsible for extraction and linkage of routinely collected clinical data required for the project and have helped develop the data processing plan and gain required approvals. Dr Rachael Wood and the COP study team at Public Health Scotland have an established research database from a population-wide Scottish birth cohort of infants born during the pandemic and have produced several publications from this, including neonatal data. They helped advise on how their database might be further developed and used for the new project, assisting with the design of data collection processes. For the outbreak of unexplained hepatitis, PHS led the investigation in Scotland and co-ordinated all clinical, epidemiological, and research efforts to establish the cause. |
| Impact | Working with eDRIS the maternal-infant SARS-CoV-2 project has now gained required approvals and data linkage has begun. The Neonatal SARS-CoV-2 data from the COP study, which I contributed to as a co-author, is published here: https://doi.org/10.1136/archdischild-2022-324713 The results of the investigation into unexplained hepatitis are published here: https://doi.org/10.1038/s41586-023-05948-2 |
| Start Year | 2022 |