The massive outbreak of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread rapidly around the world, leading to a pandemic and an unprecedented global health emergency. The current project responds to the need to fill critical gaps in our understanding of the clinical repercussions of SARS-CoV-2 infection in pregnant women and infants, while evaluating potential consequences of maternal immune activation in this vulnerable population.

Karin Nielsen and the other team members on this project have been collaborating over the last six years to characterize the clinical and cellular effects of in utero transmission of Zika virus. They have published multiple studies looking at immunological and clinical outcomes in infants with congenital Zika virus infection^1-3, including demonstrating that below average neurodevelopment occurs in roughly one third of affected children.

The team plans to utilize existing infrastructure and scientific methods developed as part of their past studies on Zika virus to evaluate clinical and immunological outcomes in mother-infant pairs with maternal SARS-Cov-2 infection. Although SARS-CoV-2 is not frequently transmitted in utero, it induces high levels of maternal immune activation during pregnancy, particularly in patients who have more severe disease. Maternal immune activation, in turn, has been shown to be associated with adverse neurodevelopmental outcomes in offspring, including autism spectrum disorder (ASD).

The COVID-19 Outcomes in Mother-Infant Pairs (COMP) study is currently being conducted at two sites: the University of California, Los Angeles, and the Oswaldo Cruz Foundation (Fiocruz) in Brazil. More than 350 mother-infant pairs have already enrolled in the study and more than 2,500 specimens (including mother and infant serum and plasma samples, placental tissue, and maternal nasopharyngeal and rectal specimens) have been collected. The overall objective is to characterize the immunological and neurodevelopmental impact of prenatal SARS-CoV-2 infection in early childhood. A comparison population of mother-infant pairs is included to facilitate interpretation of study results. The COMP study is funded in part by an award (NIAID AI140718) from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).

The supplemental funding from SFARI will help to expand the collection of samples over time and to establish a biorepository that other researchers can use. It will also enable Nielsen and her team to assess children with antenatal COVID-19 exposure from birth until 36 months of age, including periodic neurodevelopmental assessments such as the general movements assessment, Bayley III (Bayley Scales of Infant and Toddler Development, Third Edition) and the M-CHAT (Modified Checklist for Autism in Toddlers).

1. Nielsen-Saines K. et al. Nat. Med. 25, 1213-1217 (2019) PubMed
2. Brasil P. et al. Nat. Commun. 11, 3510 (2020) PubMed
3. de Melo Espindola O. et al. J. Infect. Dis. 224, 1060-1068 (2021) PubMed