In Utero Exposure to Maternal SARS-CoV-2 Infection Is Associated With Higher Left Ventricular Mass in Toddlers.

The intrauterine environment plays a critical role in shaping chronic disease risk over the life course. We prospectively evaluated cardiometabolic outcomes in toddlers born to mothers with versus without prenatal severe acute respiratory syndrome coronavirus 2 infection. Children with in utero severe acute respiratory syndrome coronavirus 2 exposure had higher left ventricular mass in association with altered maternal immunologic indices.

Placental transfer dynamics and durability of maternal COVID-19 vaccine-induced antibodies in infants.

Completion of a COVID-19 vaccination series during pregnancy effectively reduces COVID-19 hospitalization among infants less than 6 months of age. The dynamics of transplacental transfer of maternal vaccine-induced antibodies, and their persistence in infants at 2, 6, 9, and 12 months, have implications for new vaccine development and optimal timing of vaccine administration in pregnancy. We evaluated anti-COVID antibody IgG subclass, Fc-receptor binding profile, and activity against wild-type Spike and RBD plus five variants of concern (VOCs) in 153 serum samples from 100 infants. Maternal IgG1 and IgG3 responses persisted in 2- and 6-month infants to a greater extent than the other IgG subclasses, with high persistence of antibodies binding placental neonatal Fc-receptor and FcγR3A. Lowest persistence was observed against the Omicron RBD-specific region. Maternal vaccine timing, placental Fc-receptor binding capabilities, antibody subclass, fetal sex, and VOC all impact the persistence of antibodies in infants through 12 months of age.

Helping Us Grow Stronger (HUGS)/Abrazos: a community-based initiative improved perinatal mental health in an urban cohort.

BACKGROUND: Targeted programs aimed at improving maternal mental health, particularly among those exposed to social determinants of health, are increasingly critical since the onset of the COVID-19 pandemic, yet the impact of such programs is poorly understood. OBJECTIVE: This study aimed to evaluate the impact of a novel, language-concordant community-based program on perinatal mental health. STUDY DESIGN: We conducted a prospective cohort study of peripartum individuals referred to a new community-based intervention known as Helping Us Grow Stronger (HUGS/Abrazos). Participants received up to 4 remote sessions with a cognitive behavioral therapy trained social worker, up to 3 resource navigation sessions with a community health worker, and direct relief with a grocery gift card and care package. Before and after the program, participants completed validated survey instruments to assess mental health and social determinants of health. RESULTS: A total of 178 participants were assessed after program completion, including 133 who were assessed before and after the program. The cohort was composed of 62.9% Hispanic or Latinx participants with a mean age of 29.8 year (standard error of mean, 0.46). There were high rates of food insecurity (111/178; 62.4%), experiences of discrimination (119/178; 66.9%), and SARS-CoV-2 infection (105/178; 59.0%). The program was associated with statistically significant improvements in the Edinburgh Postnatal Depression scores (baseline [mean±standard error of mean], 8.44±0.55 vs 6.77±0.51 after program completion; P=.0001) and Perceived Stress Scale scores (baseline, 15.2±0.74 vs 14.0±0.71; P=.035). Participants exposed to stressors including food insecurity and experiences of discrimination had higher baseline depression, stress, and anxiety scores. Those with experiences of discrimination, food insecurity, and SARS-CoV-2 infection during pregnancy were more likely to have improvements in mental health scores postintervention. CONCLUSION: In this diverse urban cohort, a novel community-based intervention was associated with improvements in depressive symptoms, perceived stress, and anxiety, particularly among those with social determinants of health.

SARS-CoV-2 infection elucidates unique features of pregnancy-specific immunity.

Pregnancy is a risk factor for increased severity of SARS-CoV-2 and other respiratory infections. The mechanisms underlying this risk have not been well-established, partly due to a limited understanding of how pregnancy shapes immune responses. To gain insight into the role of pregnancy in modulating immune responses at steady state and upon perturbation, we collected peripheral blood mononuclear cells (PBMC), plasma, and stool from 226 women, including 152 pregnant individuals (n = 96 with SARS-CoV-2 infection and n = 56 healthy controls) and 74 non-pregnant women (n = 55 with SARS-CoV-2 and n = 19 healthy controls). We found that SARS-CoV-2 infection was associated with altered T cell responses in pregnant compared to non-pregnant women. Differences included a lower percentage of memory T cells, a distinct clonal expansion of CD4-expressing CD8 + T cells, and the enhanced expression of T cell exhaustion markers, such as programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain-3 (Tim-3), in pregnant women. We identified additional evidence of immune dysfunction in severely and critically ill pregnant women, including a lack of expected elevation in regulatory T cell (Treg) levels, diminished interferon responses, and profound suppression of monocyte function. Consistent with earlier data, we found maternal obesity was also associated with altered immune responses to SARS-CoV-2 infection, including enhanced production of inflammatory cytokines by T cells. Certain gut bacterial species were altered in pregnancy and upon SARS-CoV-2 infection in pregnant individuals compared to non-pregnant women. Shifts in cytokine and chemokine levels were also identified in the sera of pregnant individuals, most notably a robust increase of interleukin-27 (IL-27), a cytokine known to drive T cell exhaustion, in the pregnant uninfected control group compared to all non-pregnant groups. IL-27 levels were also significantly higher in uninfected pregnant controls compared to pregnant SARS-CoV-2-infected individuals. Using two different preclinical mouse models of inflammation-induced fetal demise and respiratory influenza viral infection, we found that enhanced IL-27 protects developing fetuses from maternal inflammation but renders adult female mice vulnerable to viral infection. These combined findings from human and murine studies reveal nuanced pregnancy-associated immune responses, suggesting mechanisms underlying the increased susceptibility of pregnant individuals to viral respiratory infections.