Background: The coronavirus disease (COVID-19) first identified in Wuhan in December 2019 became a pandemic within a few months of its discovery. The impact of COVID-19 is due to both its rapid spread and its severity, but the determinants of severity have not been fully delineated. Objective: Identify factors associated with hospitalization and disease severity in a racially and ethnically diverse cohort of COVID-19 patients. Methods: We analyzed data from COVID-19 patients diagnosed at the University of Cincinnati health system from March 13, 2020 to May 31, 2020. Severe COVID-19 was defined as admission to intensive care unit or death. Logistic regression modeling adjusted for covariates was used to identify the factors associated with hospitalization and severe COVID-19. Results: Among the 689 COVID-19 patients included in our study, 29.2% were non-Hispanic White, 25.5% were non-Hispanic Black, 32.5% were Hispanic, and 12.8% were of ‘Other’ race/ethnicity. About 31.3% of patients were hospitalized and 13.2% had severe disease. In adjusted analyses, the sociodemographic factors associated with hospitalization and/or disease severity included older age, non-Hispanic Black or Hispanic race/ethnicity (compared non-Hispanic White), and smoking. The following comorbidities: diabetes, hypercholesterolemia, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, cardiovascular diseases, osteoarthritis, and vitamin D deficiency, were associated with hospitalization and/or disease severity. Hematological disorders such as anemia, coagulation disorders, and thrombocytopenia were associated with higher odds of both hospitalization and disease severity. Conclusion: This study confirms race and ethnicity as predictors of severe COVID-19 and identifies clinical risk factors not previously reported such a vitamin D deficiency, hypercholesterolemia, osteoarthritis, and anemia.

The consumption of human milk by a breastfeeding infant is associated with positive health outcomes, including lower risk of diarrheal disease, respiratory disease, otitis media, and in later life, less risk of chronic disease. These benefits may be mediated by antibodies, glycoproteins, glycolipids, oligosaccharides, and leukocytes. More recently, human milk extracellular vesicles (hMEVs) have been identified. HMEVs contain functional cargos, i.e., miRNAs and proteins, that may transmit information from the mother to promote infant growth and development. Maternal health conditions can influence hMEV composition. This review summarizes hMEV biogenesis and functional contents, reviews the functional evidence of hMEVs in the maternal–infant health relationship, and discusses challenges and opportunities in hMEV research.

Bifidobacterium species are beneficial and dominant members of the breastfed infant gut microbiome; however, their health benefits are partially species-dependent. Here, we characterize the species and subspecies of Bifidobacterium in breastfed infants around the world to consider the potential impact of a historic dietary shift on the disappearance of B. longum subsp. infantis in some populations. Across populations, three distinct patterns of Bifidobacterium colonization emerged: (1) The dominance of Bifidobacterium longum subspecies infantis, (2) prevalent Bifidobacterium of multiple species, and (3) the frequent absence of any Bifidobacterium. These patterns appear related to a country’s history of breastfeeding, with infants in countries with historically high rates of long-duration breastfeeding more likely to be colonized by B. longum subspecies infantis compared with infants in countries with histories of shorter-duration breastfeeding. In addition, the timing of infant colonization with B. longum subsp. infantis is consistent with horizontal transmission of this subspecies, rather than the vertical transmission previously reported for other Bifidobacterium species. These findings highlight the need to consider historical and cultural influences on the prevalence of gut commensals and the need to understand epidemiological transmission patterns of Bifidobacterium and other major commensals.

A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme (“secretors”), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme. Similarly, maternal secretor status influences the abundance of a breastfeeding mother’s fucosylated milk oligosaccharides. We compared the impact of maternal secretor status, measured by FUT2 genotype, and infant secretor status, measured by FUT2 genotype and phenotype, on early infant fecal microbiome samples collected from 2-month-old exclusively breastfed infants (n = 59). Infant secretor status (19% non-secretor, 25% low-secretor, and 56% full-secretor) was more strongly associated with the infant microbiome than it was with the maternal FUT2 genotype. Alpha diversity was greater in the full-secretors than in the low- or non-secretor infants (p = 0.049). Three distinct microbial enterotypes corresponded to infant secretor phenotype (p = 0.022) and to the dominance of Bifidobacterium breve, B. longum, or neither (p < 0.001). Infant secretor status was also associated with microbial metabolic capacity, specifically, bioenergetics pathways. We concluded that in exclusively breastfed infants, infant—but not maternal—secretor status is associated with infant microbial colonization and metabolic capacity.

Background: Black mothers in the United States have shorter breastfeeding (BF) durations and less exclusive breastfeeding (EBF) than others. The factors underlying these disparities require investigation. Methods: Using longitudinal data from a CDC-sponsored birth cohort in Cincinnati, Ohio, we analyzed the factors mediating racial disparity in BF outcomes. Study mothers were enrolled in prenatal clinics associated with two large birth hospitals. Analysis was restricted to racial groups with sufficient numbers in the cohort, non-Hispanic Black (n = 92) and White (n = 113) mothers, followed to at least 6 months postpartum. Results: Black mothers were 25 times more likely to reside in socioeconomically deprived neighborhoods and 20 times more likely to have an annual household income <$50,000/year than White mothers (p < 0.001). The gap in EBF for 6 weeks was 45 percentage points by racial group (13%—Black mothers versus 58%—White mothers, p < 0.001); in any BF at 6 months was 37 percentage points (28%—Black mothers versus 65%—White mothers, p < 0.001); and in mothers meeting their own intention to BF at least 6 months was 51 percentage points (29%—Black mothers versus 80%—White mothers, p < 0.001). Racial disparity in EBF at 6 weeks was mediated in logistic regression models by inequities in socioeconomic position, maternal hypertension, and BF intention. Racial disparities in BF at 6 months or meeting 6-month BF intention were mediated by inequities in socioeconomic position, maternal obesity, and EBF at 6 weeks. Not all BF disparities could be explained by models used in these analyses. Conclusions: Efforts to lessen BF disparities should address the underlying structural inequities that disproportionately affect Black mothers and children, should incorporate maternal health, and focus on breastfeeding exclusivity and duration. Few Black mothers achieved EBF at 6 weeks, which contributed to disparity in BF duration. Greater attention to Black mother–infant pairs is a public health priority.

Background: Acute gastroenteritis (AGE) and acute respiratory infections (ARIs) cause significant pediatric morbidity and mortality. Developing childhood vaccines against major enteric and respiratory pathogens should be guided by the natural history of infection and acquired immunity. The United States currently lacks contemporary birth cohort data to guide vaccine development. Objective: The PREVAIL (Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal) Cohort study was undertaken to define the natural history of infection and immune response to major pathogens causing AGE and ARI in US children. Methods: Mothers in Cincinnati, Ohio, were enrolled in their third trimester of pregnancy, with intensive child follow-up to 2 years. Blood samples were obtained from children at birth (cord), 6 weeks, and 6, 12, 18, and 24 months. Whole stool specimens and midturbinate nasal swabs were collected weekly and tested by multipathogen molecular assays. Saliva, meconium, maternal blood, and milk samples were also collected. AGE (≥3 loose or watery stools or ≥1 vomiting episode within 24 hours) and ARI (cough or fever) cases were documented by weekly cell phone surveys to mothers via automated SMS text messaging and review of medical records. Immunization records were obtained from registries and providers. follow-up ended in October 2020. Pathogen-specific infections are defined by a PCR-positive sample or rise in serum antibody. Results: Of the 245 enrolled mother–child pairs, 51.8% (n=127) were White, 43.3% (n=106) Black, 55.9% (n=137) publicly insured, and 86.5% (n=212) initiated breastfeeding. Blood collection was 100.0% for mothers (n=245) and 85.7% for umbilical cord (n=210). A total of 194/245 (79.2%) mother–child pairs were compliant based on participation in at least 70% (≥71/102 study weeks) of child-weeks and providing 70% or more of weekly samples during that time, or blood samples at 18 or 24 months. Compliant participants (n=194) had 71.0% median nasal swab collection (IQR 30.0%-90.5%), with 98.5% (191/194) providing either an 18- or 24-month blood sample; median response to weekly SMS text message surveys was 95.1% (IQR 76.5%-100%). Compliant mothers reported 2.0 AGE and 4.5 ARI cases per child-year, of which 25.5% (160/627) and 38.06% (486/1277) of cases, respectively, were medically attended; 0.5% of AGE (3/627) and 0.55% of ARI (7/1277) cases were hospitalized. Conclusions: The PREVAIL Cohort demonstrates intensive follow-up to document the natural history of enteric and respiratory infections and immunity in children 0-2 years of age in the United States and will contribute unique data to guide vaccine recommendations. Testing for pathogens and antibodies is ongoing. International Registered Report Identifier (IRRID): RR1-10.2196/22222