Progesterone induced immune modulation during pregnancy - supplemental research in COVID-19

Project Summary: Despite pandemic spread of the novel coronavirus, COVID-19, significant knowledge gapsremain especially for Center for Disease Control designated high risk populations such as pregnant women. Ofhigh clinical importance is the susceptibility of pregnant women to infection, the direct risk to the mother and theindirect impact of disease severity (including preterm delivery and fetal death) on the pregnancy. While muchresearch is being pursued from translational research to intervention trials for COVID-19, pregnant women arealmost universally excluded from intervention and observational trials. Research in pregnant women is of thehighest priority. The ability to understand which pregnant women are at risk for severe COVID-19 disease, weeksif not months prior to clinical symptomatology, could provide novel and important windows for preventativeinterventions to limit maternal morbidity and mortality. Additionally, if clinical data emerges that the majority ofpregnant women may actually be more tolerant of SARS-CoV-2 compared to other respiratory viruses,understanding the immunological changes of pregnancy may provide insights as to ways to modulate diseaserisk in non-pregnant populations. To address all of these gaps in knowledge, large maternal cohorts withbiospecimens and detailed phenotyping in areas of high prevalence of COVID-19 are required. The establishedinvestigative team and research infrastructure for two active maternal cohorts designed for prospective analysisof maternal immunity during pregnancy (R01-A1145840) can now be leveraged to investigate deep immunephenotyping of pregnant women prior to acquisition of COVID-19. We will be able to investigate how differentimmune phenotypes predict COVID-19 infection in pregnant women. Complementing the existing expertise inperinatology and immunology for the parent RO1, this study add the immunology and virology expertise at theUniversity of Pennsylvania. We propose to investigate the following three scientifically important aims: 1) whethermaternal immune profiles are associated with acquisition and severity of COVID19 in pregnant women; 2)whether immune profiles in pregnant women with active COVID19 are similar to non-pregnant women with similardisease severity and 3) whether immune profiles in the 2nd trimester of pregnancy are associated with adversereproductive outcomes. All women enrolled will have extensive metadata collected with adjudication of COIVD-19 status and severity as well as detailed clinical phenotyping of obstetrical outcomes. Deep immunephenotyping will provide innovative and rigorous investigation of innate and adaptive immune states duringpregnancy and will be interrogated regarding their association with COVID19 phenotypes. We will alsoinvestigate the presence of maternal antibodies (IgG and IgM against SARS-CoV-2) at the same time point asimmune profiling. We have the necessary expertise, the research infrastructure and the patient population tocomplete the proposed study in the 2 year time line with a 400 person cohort. This study address many significantgaps in knowledge including essential questions regarding the immune biology in pregnancy.