Status: Funded - Open
Karen Jacobson, MD, MPH
BACKGROUND: SARS-CoV-2 and malaria in pregnancy both cause preterm birth and low birth weight, leading to poor growth in infancy. SARS-CoV-2’s impacts on pregnant women living in malaria endemic settings, and long-term growth and neurodevelopment effects on infants with gestational exposure to SARS-CoV-2, remains unclear. Systemic maternal inflammation including activation of IL-1 signaling pathway, which is associated with viral and parasitic infection as well as altered neurodevelopment, may be involved. GAP: This proposal will address the following research gaps: 1) How does exposure to both malaria and SARS-CoV-2 in pregnancy impact infant development, and 2) Is the effect of gestational SARS-CoV-2 on infant development mediated by specific maternal inflammatory pathways? HYPOTHESIS: I hypothesize that infants exposed to gestational SARS-CoV-2 will have poor growth (stunting, underweight, and wasting) and lower neurocognitive test scores in infancy compared with unexposed infants, that malaria and SARS-CoV-2 in pregnancy will have synergistic negative effects, and that these adverse effects will be mediated by pro-inflammatory maternal cytokines. METHODS: In this nested cohort study of maternal/infant dyads enrolled in a antimalarial chemoprevention trial in Busia District, Uganda, we will perform serial testing of stored maternal plasma samples and cord blood to determine incidence of SARS-CoV-2 seroconversion during pregnancy, and we will compare infant growth, neurocognitive test scores on the Bayley Scales of Infant and Toddler Development (3rd ed), and maternal immune proteomic profiles in pregnancies exposed to SARS-CoV-2 and/or malaria. RESULTS: Pending. IMPACT: This study will characterize SARS-CoV-2/malaria interactions in a setting largely excluded from global anti-SARS-CoV-2 efforts (e.g. testing, vaccines, research), examining the impact on long term infant outcomes, which are still unknown. Our data will immediately inform prioritization of scarce resources for early screening and interventions for growth and developmental delays in infants in malaria-endemic settings like Uganda, and could potentially identify diagnostic or therapeutic targets for future clinical interventions.