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

PROJECT SUMMARY ABSTRACTDespite pandemic spread of the novel coronavirus, COVID-19, too little is known about the epidemiology ofinfection, transmission, and susceptibility to severe infection. What we do know about COVID-19 is largelybased 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 childrenremain largely undefined. Filling these fundamental gaps in knowledge regarding infection susceptibility inthese essential developmental time points require maternal-infant cohorts capable of simultaneously screeningclinical symptoms and COVID-19 virus acquisition. The established infrastructure for two maternal-infantcohorts 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, clinicalmanifestations, disease severity and immune correlates of COVID-19 infection in pregnant women, mothersand 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 textmessaging), weekly nasal swab sampling, and virus identification in real-time through a courier network in theCincinnati metro area. Supplemental funding through this Notice of Special Interest regarding the availability ofUrgent Competitive Revision for Research on the 2019 Novel Coronavirus (2019-nCoV; NOT-AI-20-034) willexpand this analysis to include COVID-19 epidemiological surveillance for pregnant women, mothers, infantsand children (Aim 1), plus additional collection of specimens for immunological assays at the time of infectioncompared with recruitment (pre-infection) and infection-community spread resolution (Aim 2). Epidemiologicalsurveillance 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 ofmaternal immunity transferred either vertically and/or postnatally through breast milk on infant COVID-19infection susceptibility. Key specimens will include PBMCs that could be used to identify gains and losses ofeach cell population, plasma/serum for analysis of qualitative/quantitative shifts in virus-specific antibodies ateach time point. An additional "Tempus" tube allowing stabilization of intracellular RNA from cells in wholeblood will be collected at the time of infection for gene expression analysis. We envision that as COVID-19immunological assays are being developed and become more standardized, these samples that link COVID-19infection tempo and severity of each individual will provide an invaluable resource to investigate theimmunological changes associated with asymptomatic to severe infection in pregnant women, mothers andtheir children and their relationship in each maternal-infant dyad.