ABSTRACT
On March 11, 2020, the World Health Organization declared the novel coronavirus (COVID-19) outbreak a global pandemic. In April 2020, the Pregnancy and Infant Linked Outcomes Team (PILOT) was established within the Centers for Disease Control and Prevention's (CDC) COVID-19 response structure, specifically to focus on better understanding the impact of COVID-19 in pregnancy. A total of 71 CDC staff deployed to PILOT, collectively contributing more than 99,000 hours to the response over the course of the team's 25-month activation. PILOT led or collaborated on the publication of over 40 manuscripts, managed several clinical guidance documents, and coordinated and provided subject matter expertise to three funded research studies with academic partners. The team developed six CDC webpages, a toolkit for pregnant people and new parents, and disseminated scientific findings with over 350 social media posts on Facebook, Twitter, Snapchat, LinkedIn, and Instagram with nearly 77 million total impressions. In this, we will summarize the work of PILOT, and other parts of the CDC COVID-19 response, including teams focused on vaccine effectiveness and safety, and surveillance and research activities outside of the CDC. We will review several key contributions to our understanding of COVID-19 in pregnancy: (1) pregnant people are at greater risk of severe illness from COVID-19, including hospitalization, admission to an intensive care unit, and the need for mechanical ventilation, compared with nonpregnant women of reproductive age;(2) pregnant people with COVID-19 are more likely to experience complications that can affect their pregnancy and developing baby, including stillbirth and preterm delivery, compared to pregnant people without COVID-19;(3) there are no recognized maternal or fetal adverse effects of COVID-19 vaccines in pregnancy;and (4) COVID-19 vaccine during pregnancy is effective in preventing severe illness, hospitalization and death among pregnant people, as well as preventing severe illness in infants up to age six months.
ABSTRACT
Background: Pregnant individuals are at increased risk of coronavirus disease 2019 (COVID-19) hospitalization and death, and primary and booster COVID-19 vaccination is recommended for this population. Method(s): Among a cohort of pregnant individuals who received prenatal care at 3 healthcare systems in the United States, we estimated the cumulative incidence of hospitalization with symptomatic COVID-19 illness. We also identified factors associated with COVID-19 hospitalization using a multivariable Cox proportional hazards model with pregnancy weeks as the timescale and a time-varying adjustor that accounted for severe acute respiratory syndrome coronavirus 2 circulation;model covariates included site, age, race, ethnicity, insurance status, prepregnancy weight status, and selected underlying medical conditions. Data were collected primarily through medical record extraction. Result(s): Among 19 456 pregnant individuals with an estimated due date during 1 March 2020-28 February 2021, 75 (0.4%) were hospitalized with symptomatic COVID-19. Factors associated with hospitalization for symptomatic COVID-19 were Hispanic ethnicity (adjusted hazard ratio [aHR], 2.7 [95% confidence interval {CI}, 1.3-5.5]), Native Hawaiian or Pacific Islander race (aHR, 12 [95% CI, 3.2-45.5]), age <25 years (aHR, 3.1 [95% CI, 1.3-7.6]), prepregnancy obesity (aHR, 2.1 [95% CI, 1.1-3.9]), diagnosis of a metabolic disorder (aHR, 2.2 [95% CI, 1.2-3.8]), lung disease excluding asthma (aHR, 49 [95% CI, 28-84]), and cardiovascular disease (aHR, 2.6 [95% CI, 1.5-4.7]). Conclusion(s): Although hospitalization with symptomatic COVID-19 was uncommon, pregnant individuals should be aware of risk factors associated with severe illness when considering COVID-19 vaccination. Copyright © 2022 Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is written by (a) US Government employee(s) and is in the public domain in the US.
ABSTRACT
Background. Natural SARS-CoV-2 infection results in anti-nucleocapsid (N) and anti-spike (S) antibody (Ab) development. Anti-S Ab response (conferred by infection and/or vaccination) is more closely associated with protection. We evaluated anti-N/S Ab responses in vaccinated (> 1 dose) and unvaccinated pregnant people with prior SAR-CoV-2 infection. Methods. During January 2021-March 2022, we enrolled participants with SARS-CoV-2 infection identified in pregnancy (26 via anti-N IgG+;52 via prior RT-PCR+). Baseline, 1, 2, 3, 6, and 12 months, and delivery samples were tested for anti-N (index >= 1.4 positive) and anti-S (>= 50 AU/mL positive) IgG Ab by Abbott Architect. Kaplan-Meier methods were used to measure Ab response duration. Results. Among 78 participants, 62 (79%) enrolled in pregnancy (median 27 weeks gestation), and 16 (21%) at delivery/postpartum (median 2 weeks);34 (44%) had received >=1 vaccine prior to initial Ab testing. At baseline, 59 (75%) participants had concordant anti-N/S positive results (median anti-N index 3.58 [IQR 2.01-5.82], median anti-S 5529 AU/ml [IQR 687-25000]). Anti-S IgG was higher (25000 vs 774, p< 0.001) among participants receiving >=1 vaccine vs no vaccine, while anti-N IgG indices were similar. Among 59 participants with initial anti-N IgG+ results, median time to anti-N IgG negative results was 31 weeks after first RT-PCR+ (median 17 weeks after first anti-N IgG+ result). Only 1 (unvaccinated) participant had an anti-S IgG negative result by 22 weeks after first RT-PCR+ result. Among 30 participants with delivery samples (median 16 weeks after RT-PCR+, 12 weeks after baseline anti-N IgG+ samples), 15 (52%) remained anti-N IgG+;29 (97%) remained anti-S IgG+. Anti-S IgG was higher (25000 vs 826 AU/ml, p< 0.001) among participants receiving >= 1 vaccine vs. no vaccine prior to delivery. Conclusion. Among pregnant persons with prior SARS-CoV-2 infection, duration of anti-S IgG response was longer than anti-N IgG irrespective of vaccine status;vaccination during pregnancy was associated with higher anti-S levels at baseline and delivery. While anti-S IgG were detectable for >= 6 months, longer term follow-up is needed to assess durability of hybrid immunity vs. infection alone and has implications for maternal and infant protection.
ABSTRACT
Background: Longitudinal assessment of SARS-CoV-2 antibody (Ab) response during pregnancy after infection and transplacental transfer may inform durability of maternally derived Ab for mothers and infants. Methods: Between October 2020-September 2021, pregnant people testing SARS-CoV-2 IgG positive by Abbott Architect chemiluminescent immunoassay (CMIA) for anti-nucleocapsid (N) antibody (semi-quantitative index ≥1.4 considered IgG+) during pregnancy or delivery in a seroprevalence study, or identified with RT-PCR+ results via medical records, were invited to enroll in a longitudinal evaluation of maternal Ab responses and transplacental transfer. Maternal blood collected at 1, 2, 3, and 6 months after enrollment and maternal and cord blood collected at delivery were tested with the same assay. Results: Among 40 participants testing IgG+ for anti-N, 31 (78%) had a prior RT-PCR+ result. Median age was 32 years (IQR 29-35);27 (68%) enrolled during pregnancy at median 18 weeks gestation (IQR 13-33), while 13 (33%) enrolled at delivery or early postpartum. Median Abbott index was 3.06 (IQR 1.96-5.74) at first IgG+ result obtained at a median of 9 weeks (IQR 4-16) after RT-PCR+ result, for those with a known RT-PCR. Among 23 participants with ≥2 samples, 50% had IgG results below positivity threshold at median 17 weeks (IQR 12-28) after first IgG+ result (Figure). Seventeen mother-infant pairs had delivery samples collected at median 66 days (IQR 60-71 days) from maternal RT-PCR+ result. Six (35%) maternal samples remained IgG+ (median Abbott index 2.97 [IQR 2.35-7.01]) at delivery (gestational age 30-40 weeks) with all 6 paired cord sera testing IgG+ (median Abbott index 4.30 [IQR 2.93-7.22]). Median placental transfer ratio of maternally derived IgG Abs based on a positive Abbott index was 1.13 (95%CI 0.98-1.30) among mothers with samples remaining IgG+ at delivery. Conclusion: Within 4 months after first IgG+ result primarily in second trimester, about half of pregnant persons had SARS-CoV-2 IgG anti-N Ab levels below the Abbott CMIA positive threshold. Among evaluable mother-infant pairs, two-thirds of mothers no longer tested anti-N IgG+ at delivery. Transplacental transfer of maternal antibodies was confirmed in all infants born to mothers with samples remaining IgG+ at delivery. Durability of maternal SARS-CoV-2 Ab response and transplacental transfer following infection has implications for maternal and neonatal susceptibility to SARS-CoV-2 infection.
ABSTRACT
The first coronavirus disease (COVID-19) vaccines in the United States were the messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). Pregnant persons were excluded from the original Emergency Use Authorization (EUA) issued by the Federal Drug Administration (FDA) in December 2020. Pregnant persons with COVID-19 are at increased risk for adverse pregnancy outcomes compared with pregnant persons without COVID-19. This study presents preliminary findings of mRNA COVID-19 vaccine safety in pregnant persons from the United States. To conduct this study, the researchers extracted data from 3 different US vaccine safety monitoring systems: the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS). V-safe asks participants to report local and systemic signs and symptoms as mild, moderate, or severe during daily surveys. Women were eligible if they received their mRNA vaccination during pregnancy or during the preconception period, defined as 30 days before the last menstrual period through 14 days after, and were 18 years of age or older. Participant-reported pregnancy outcomes were spontaneous pregnancy loss (defined as spontaneous abortion and stillbirth) and neonatal outcomes (such as preterm birth, congenital anomalies, small size for gestational age, and neonatal death). Data were obtained through December 14, 2020, to February 28, 2021. In all, 35,691 v-safe participants ages 16 to 54 years identified themselves as pregnant. The majority of enrolled participants were between the ages of 25 and 44 years (98.8%), non-Hispanic White (79.0%), and did not report a COVID-19 diagnosis during pregnancy (97.6%). Overall, 92 (2.3%) of participants received their first vaccination dose during the preconception period, 1132 (28.6%) in the first trimester, 1714 (43.3%) in the second trimester, and 1019 (25.7%) in the third trimester. In terms of adverse effects, injection site pain was described more among pregnant persons compared with nonpregnant women. Headache, myalgia, chills, and fever were reported less often among pregnant persons compared with nonpregnant people. Of the 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy. Of these, 827 completed pregnancies, 115 (13.9%) resulted in a pregnancy loss, and 712 (86.1%) resulted in a live birth (mainly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%);no neonatal deaths were reported. There were 221 pregnancy-related adverse events reported to VAERS, of which the most frequently reported event was spontaneous abortion (46 cases). No congenital anomalies were reported. Of note, the proportions of adverse pregnancy and neonatal outcomes in the v-safe pregnancy database were similar to those published before the COVID-19 pandemic. The findings from this study did not show obvious safety concerns among pregnant persons who received mRNA COVID-19 vaccines. More longitudinal follow-up and studies including larger numbers of women vaccinated earlier in pregnancy are needed to better inform outcomes. Further, new evidence has shown transplacental transfer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies after maternal COVID-19 vaccination during the third trimester. This evidence suggests that maternal vaccination might provide some protection to the neonate. However, more data are needed to make evaluations on the level of protection.