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Principal Investigator: Mary Catherine Cambou
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2023
Award: $203,580
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
While the clinical spectrum of SARS-CoV-2 infection in pregnancy ranges from asymptomatic to critical disease,
pregnancy itself augments the risk of severe and critical COVID-19. The leading obstetrical societies in the U.S.
recommend COVID-19 messenger RNA (mRNA) vaccination in pregnancy to prevent severe disease.
Furthermore, passive immunity to the neonate via transplacental transfer of immunoglobulin G (IgG) is critically
important during the first six months of life, particularly as the COVID-19 vaccines are approved only for children
>six months of age. Hybrid immunity, defined as vaccine-induced immunity before or after natural infection with
SARS-CoV-2, produces a more robust response in non-pregnant populations than either type in isolation. The
long-term inflammatory and immunologic responses to SARS-CoV-2 hybrid immunity in pregnancy, a state
marked by tightly regulated T cell control and immune modulation, compared to natural infection are unknown.
As SARS-CoV-2 becomes endemic, this proposal will address a gap in the literature that has focused primarily
on natural SARS-CoV-2 infection in pregnancy compared to vaccine-induced immunity. Leveraging the existing
COVID-19 Outcomes in Mother-Infant Pairs (COMP) study, a longitudinal cohort that follows 225 mother-infant
dyads diagnosed with SARS-CoV-2 infection in pregnancy, the proposal seeks to better understand the long-
term consequences of SARS-CoV-2 hybrid immunity in pregnancy. We hypothesize that SARS-CoV-2 hybrid
immunity compared to natural infection in pregnancy confers protection against postpartum complications, leads
to less maternal systemic inflammation, and results in more robust immune responses in mother-infant pairs.
The study aims are: 1) to estimate the prevalence and risk factors of peripartum and delayed postpartum
complications of COVID-19 in pregnancy between those with SARS-CoV-2 hybrid immunity, and those with
natural infection; 2) to compare the systemic inflammatory landscapes, as measured by cytokine profiles, of
pregnant women with SARS-CoV-2 hybrid immunity and natural infection at delivery and one year postpartum;
and 3) to evaluate cellular and humoral immune responses to the ancestral and Omicron (BA.5) strains following
COVID-19 in pregnancy at delivery and six months postpartum in mother-infant dyads with SARS-CoV-2 hybrid
immunity compared to natural infection. The K23 will support Dr. Cambou to develop advanced skills in 1) applied
immunology, 2) perinatal infections, and 3) cytokine analysis, in order to become an effective translational
physician-scientist. Dr. Karin Nielsen, a world-renowned pediatric infectious diseases (ID) expert in perinatal
infections, will serve as the primary mentor. Co-mentors Drs. Otto O. Yang and Grace Aldrovandi, experts in
viral immunology, have over 20 years of continuous NIH funding and proven track records of successful
mentorship. Co-mentor Dr. Debika Bhattacharya will offer guidance as an adult ID clinical researcher in perinatal
viral infections. The K23 will allow Dr. Cambou to carve out a unique niche of multidisciplinary research blending
immunology with viral infections in pregnancy, in order to launch her career as an independent investigator.
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