COVID-19 Epidemiology and Immune-Pathogenesis in Pregnant Women, Mothers and Children

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PROJECT SUMMARY ABSTRACT Despite pandemic spread of the novel coronavirus, COVID-19, too little is known about the epidemiology of infection, transmission, and susceptibility to severe infection. What we do know about COVID-19 is largely based on severe disease after infection in the elderly, and adults with co-morbid conditions. Unfortunately, susceptibility to severe infection, disease burden, and transmission in pregnant women, infants and children remain largely undefined. Filling these fundamental gaps in knowledge regarding infection susceptibility in these essential developmental time points require maternal-infant cohorts capable of simultaneously screening clinical symptoms and COVID-19 virus acquisition. The established infrastructure for two maternal-infant cohorts designed for prospective analysis of infant influenza acquisition and immunity (U01AI144673; IMPRINT) and respiratory and enteric infection (CDC sponsored PREVAIL; https://www.cdc.gov/surveillance/nvsn/prevail.html) can be leveraged to investigate the incidence, clinical manifestations, disease severity and immune correlates of COVID-19 infection in pregnant women, mothers and their children. The logistics are already in place for recruiting women during their third pregnancy trimester, and following the natural history of infection in infants through twice weekly symptom surveillance (by text messaging), weekly nasal swab sampling, and virus identification in real-time through a courier network in the Cincinnati metro area. Supplemental funding through this Notice of Special Interest regarding the availability of Urgent Competitive Revision for Research on the 2019 Novel Coronavirus (2019-nCoV; NOT-AI-20-034) will expand this analysis to include COVID-19 epidemiological surveillance for pregnant women, mothers, infants and children (Aim 1), plus additional collection of specimens for immunological assays at the time of infection compared with recruitment (pre-infection) and infection-community spread resolution (Aim 2). Epidemiological surveillance will include analysis of infection severity and duration of virus shedding relative to postnatal age, transmission of virus between mother and child plus other household contacts, and the potential impacts of maternal immunity transferred either vertically and/or postnatally through breast milk on infant COVID-19 infection susceptibility. Key specimens will include PBMCs that could be used to identify gains and losses of each cell population, plasma/serum for analysis of qualitative/quantitative shifts in virus-specific antibodies at each time point. An additional “Tempus” tube allowing stabilization of intracellular RNA from cells in whole blood will be collected at the time of infection for gene expression analysis. We envision that as COVID-19 immunological assays are being developed and become more standardized, these samples that link COVID-19 infection tempo and severity of each individual will provide an invaluable resource to investigate the immunological changes associated with asymptomatic to severe infection in pregnant women, mothers and their children and their relationship in each maternal-infant dyad.