Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design

Importance Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. Methods RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. Discussion RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero

Predicting risk of bacterial vaginosis: the role of race, smoking and corticotropin-releasing hormone-related genes

Bacterial vaginosis (BV) is one of the most prevalent vaginal disorders in adult women and is associated with adverse pregnancy outcomes such as pre-term birth. Genetic factors, particularly in genes involved in inflammation and infection, are associated with this condition. Additionally, environmental risk factors including stress and smoking are associated with BV. The purpose of this study was to identify genetic variants in stress-related genes such as corticotropin-releasing hormone (CRH), receptor 1, receptor 2 and binding protein (CRH-BP) that associate with BV. Also gene–environment effects with smoking are determined. BV was quantified using the Nugent score in 82 white and 65 black women in the first trimester of pregnancy. Associations between Nugent score, genotype and smoking were analyzed using Kruskal–Wallis and Wilcoxon rank sum non-parametric tests. In white women, non-smokers with the CT genotype at CRH-BP + 17487 have lower Nugent scores (median: 0, range: 0–0) than non-smokers with the TT genotype (median: 2, range: 0–8) (P = 0.002); whereas smokers with the CT genotype have higher Nugent scores (median: 6, range: 0–10) than smokers with the TT genotype (median: 1, range: 0–10) (P = 0.021). In black women, the AG genotype at CRH + 3362 or CRH − 1667 is associated with lower Nugent scores (median for both: 3, range: 0–10) compared with the homozygous genotypes (median for each homozygous genotype: 8, range: 0–10). Also, in black women, models remain significant after adjusting for smoking (P = 0.04 for both). These data indicate that susceptibility to BV is affected by patterns of genetic variation in stress-related genes and smoking plays an important role