Provider confidence in counseling preconception, pregnant, and postpartum patients regarding COVID-19 vaccination: A cross-sectional survey study.

Background and Aims: Healthcare provider counseling surrounding COVID-19 vaccine in pregnancy and lactation is essential to vaccination uptake in this population; however, provider knowledge and confidence are not well characterized. We aimed to assess knowledge and confidence in COVID-19 vaccine counseling among practitioners who provide care to pregnant persons and to describe factors associated with confidence in counseling. Methods: A web-based anonymous survey was distributed via email to a cross-sectional convenience sample of Obstetrics and Gynecology, Primary Care, and Internal Medicine faculty at three hospitals in a single healthcare network in Massachusetts, United States. Individual demographics and institution-specific variables were included in the survey along with questions assessing both attitudes toward COVID-19 illness and confidence in counseling regarding the use of the vaccine in pregnancy. Results: Almost all providers (151, 98.1%) reported that they received a COVID-19 vaccine, and most (111, 72.1%) reported that they believe the benefits of the vaccine in pregnancy outweigh the risks. Forty-one (26.6%) reported feeling very confident in counseling patients who primarily speak English about the evidence for messenger ribonucleic acid vaccination in pregnancy, and 36 (23%) reported feeling very confident in counseling patients who are not primarily English-speaking. Forty-three providers (28.1%) expressed strong confidence in their comfort talking to individuals with vaccine hesitancy based on historic and continued racism and systemic injustices. The sources that survey respondents most used to find information regarding COVID-19 vaccination in pregnancy were the Centers for Disease Control (112, 74.2%), hospital-specific resources (94, 62.3%), and the American College of Obstetricians and Gynecologists (82, 54.3%). Conclusion: Ensuring that providers feel comfortable bridging the gap between their belief that the vaccine is beneficial for pregnant patients and their comfort with holding conversations with patients regarding vaccination is paramount to ensure equitable access to vaccines for pregnant patients.

Availability Versus Accessibility: Identifying COVID-19 Testing Deserts Across Massachusetts.

Throughout the COVID-19 pandemic, communities of color have faced significantly higher rates of COVID-19 infection, as well as poor clinical outcomes. These differences are driven by long-standing structural inequities that prevent effective social distancing efforts and are further exacerbated by disparities in COVID-19 testing. Our study applied the concept of "COVID-19 testing deserts" to systematically identify gaps in testing resource allocation across Massachusetts in May 2020 and March 2021. Testing deserts were identified at the census tract level, using criteria developed by the Department of Agriculture for food deserts. Testing deserts occurred more frequently in segregated Hispanic, segregated Black, mixed minority, and integrated communities, as well as in neighborhoods with low vehicle access and in federally designated Medically Underserved Areas. Segregated communities were those in which more than 50 percent of the population self-identified as non-Hispanic White, Hispanic, non-Hispanic Black, or non-Hispanic Asian, respectively. Testing deserts were overrepresented in counties with high COVID-19 incidence rates, suggesting that testing accessibility is essential for prompt COVID-19 diagnosis and self-isolation.

Perceptions and Attitudes toward COVID-19 Vaccination among Pregnant and Postpartum Individuals.

OBJECTIVE: This study aimed to characterize attitudes toward novel coronavirus disease 2019 (COVID-19) vaccination and to evaluate factors associated with vaccine uptake among pregnant individuals. STUDY DESIGN: An anonymous survey was distributed to a convenience sample of pregnant individuals receiving prenatal care at two large urban academic hospitals in a single health care network in Massachusetts. Individual demographic variables were included in the survey along with questions assessing attitudes toward COVID-19 and vaccination in pregnancy. Data were analyzed using parametric or nonparametric tests when appropriate, and associated odds ratios (OR) were calculated via univariable logistic regression. RESULTS: There were 684 surveys distributed, and 477 pregnant and postpartum individuals completed the survey, for a response rate of 69.7%. Overall, 233 (49.3%) had received or were scheduled to receive a COVID-19 vaccine. Age, White race, non-Hispanic or Latinx ethnicity, working from home, and typical receipt of the influenza vaccine were associated with COVID-19 vaccination. Further, 276 respondents (58.4%) reported that their provider recommended the COVID-19 vaccine in pregnancy; these participants were more likely to have received a vaccine (OR = 5.82, 95% confidence interval [CI]: 3.68-9.26, p < 0.005). Vaccinated individuals were less likely to be worried about the effects of the vaccine on themselves (OR = 0.18, 95% CI: 0.12-0.27, p < 0.005) or their developing babies (OR = 0.17, 95% CI: 0.11-0.26, p < 0.005). Unvaccinated individuals were less likely to report that it is easy to schedule a COVID-19 vaccine (OR = 0.56, 95% CI: 0.34-0.93, p = 0.02), to travel to receive a vaccine (OR = 0.19, 95% CI: 0.10-0.36, p < 0.005), and to miss work to receive a vaccine (OR = 0.30, 95% CI: 0.18-0.48, p < 0.005). CONCLUSION: Strategies are needed to improve patient education regarding vaccine side effects and safety in pregnancy. Policy changes should focus on making it feasible for patients to schedule a vaccine and miss work without loss of pay to get vaccinated. KEY POINTS: · There were racial and ethnic disparities in COVID-19 vaccination.. · Unvaccinated respondents were more likely to be concerned about vaccine effects for themselves or their growing babies.. · Unvaccinated respondents cited work and scheduling-related barriers to vaccination, indicating areas for advocacy..

Placental pathology from COVID-19-recovered (nonacute) patients.

Placental pathology can identify characteristic features of specific infectious pathogens. The histopathology of acute SARS-CoV-2 placental infection and exposure without infection has been well described. However, whether the characteristic placental pathology persists after the acute phase of the infection is less clear. We retrospectively identified 67 COVID-19-recovered pregnant patients who had placental pathology available. After reviewing the gross and histopathology, we categorized the findings and studied the placentas for evidence of chronic infection by immunohistochemistry for the spike protein of the virus. We found these placentas showed significantly increased prevalence of maternal and a trend towards significance of fetal vascular malperfusion when compared to a control group of placentas examined for the sole indication of maternal group B streptococcal colonization. None of the COVID-19-recovered placentas showed expression of the viral spike protein; therefore, we found no evidence of persistent infection of the placenta in women with a history of COVID-19 during their pregnancy. We conclude that recovery from a SARS-CoV-2 infection during pregnancy puts the pregnancy at risk for specific pathology.

Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?

BACKGROUND: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. METHODS: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). RESULTS: Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. CONCLUSIONS: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.

Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses.

There is a persistent bias toward higher prevalence and increased severity of coronavirus disease 2019 (COVID-19) in males. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of COVID-19 disease in adults and play a key role in the placental antiviral response. Moreover, the interferon response has been shown to alter Fc receptor expression and therefore may affect placental antibody transfer. Here, we examined the intersection of maternal-fetal antibody transfer, viral-induced placental interferon responses, and fetal sex in pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor abundance, interferon-stimulated gene (ISG) expression, and SARS-CoV-2 antibody transfer were interrogated in 68 human pregnancies. Sexually dimorphic expression of placental Fc receptors, ISGs and proteins, and interleukin-10 was observed after maternal SARS-CoV-2 infection, with up-regulation of these features in placental tissue of pregnant individuals with male fetuses. Reduced maternal SARS-CoV-2­specific antibody titers and impaired placental antibody transfer were also observed in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

Compromised SARS-CoV-2-specific placental antibody transfer.

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.

Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study.

BACKGROUND: Pregnant and lactating women were excluded from initial coronavirus disease 2019 vaccine trials; thus, data to guide vaccine decision making are lacking. OBJECTIVE: This study aimed to evaluate the immunogenicity and reactogenicity of coronavirus disease 2019 messenger RNA vaccination in pregnant and lactating women compared with: (1) nonpregnant controls and (2) natural coronavirus disease 2019 infection in pregnancy. STUDY DESIGN: A total of 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 nonpregnant women) were enrolled in a prospective cohort study at 2 academic medical centers. Titers of severe acute respiratory syndrome coronavirus 2 spike and receptor-binding domain immunoglobulin G, immunoglobulin A, and immunoglobulin M were quantified in participant sera (n=131) and breastmilk (n=31) at baseline, at the second vaccine dose, at 2 to 6 weeks after the second vaccine, and at delivery by Luminex. Umbilical cord sera (n=10) titers were assessed at delivery. Titers were compared with those of pregnant women 4 to 12 weeks from the natural infection (n=37) by enzyme-linked immunosorbent assay. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Postvaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed-effects model, with correction for multiple comparisons, were used to assess differences among groups. RESULTS: Vaccine-induced antibody titers were equivalent in pregnant and lactating compared with nonpregnant women (pregnant, median, 5.59; interquartile range, 4.68-5.89; lactating, median, 5.74; interquartile range, 5.06-6.22; nonpregnant, median, 5.62; interquartile range, 4.77-5.98, P=.24). All titers were significantly higher than those induced by severe acute respiratory syndrome coronavirus 2 infection during pregnancy (P<.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord than maternal sera, although this finding did not achieve statistical significance (maternal sera, median, 104.7; interquartile range, 61.2-188.2; cord sera, median, 52.3; interquartile range, 11.7-69.6; P=.05). The second vaccine dose (boost dose) increased severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G, but not immunoglobulin A, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups. CONCLUSION: Coronavirus disease 2019 messenger RNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in nonpregnant women. Vaccine-induced immune responses were statistically significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic.

Importance: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection. Design, Setting, and Participants: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription-polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2. Exposures: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR. Main Outcomes and Measures: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti-SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta. Results: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti-receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti-SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti-receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted. Conclusions and Relevance: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.