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1.
Nat Commun ; 13(1): 4422, 2022 07 30.
Article in English | MEDLINE | ID: covidwho-1967602

ABSTRACT

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. Here, we evaluate the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we find time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persists during early infancy. Additionally, using phage immunoprecipitation sequencing, we find a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. Timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Female , Humans , Immunoglobulin G , Infant, Newborn , Placenta , Pregnancy , RNA, Messenger , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vaccines, Synthetic , mRNA Vaccines
2.
JCI Insight ; 7(12)2022 06 22.
Article in English | MEDLINE | ID: covidwho-1846629

ABSTRACT

Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there are limited data comparing vaccine- and infection-induced neutralizing Abs (nAbs) against COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines (from December 2020 through August 2021) were matched with 30 naturally infected women (from March 2020 through January 2021) by gestational age of exposure. Neutralization activity against the 5 SARS-CoV-2 spike sequences was measured by a SARS-CoV-2-pseudotyped spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared with WT spike protein, these nAbs were less effective against the Delta and Mu spike variants. Vaccination during the third trimester induced higher cord-nAb levels at delivery than did infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared with infection during the first trimester. The transfer ratio (cord nAb level divided by maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicits effective nAbs with differing neutralization kinetics that are influenced by gestational time of exposure.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Female , Gestational Age , Humans , Mothers , Neutralization Tests , Vaccination
4.
Front Immunol ; 12: 777103, 2021.
Article in English | MEDLINE | ID: covidwho-1528826

ABSTRACT

Background: Data regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines. Methods: From a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers' 2nd dose). Results: No severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period before achieving full immune response. PEGylated proteins were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation. Conclusions: COVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/administration & dosage , Lactation/immunology , Milk, Human/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/blood , COVID-19/prevention & control , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Infant , Infant, Newborn , Male , Middle Aged
5.
Clin Infect Dis ; 73(9): e2810-e2813, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501000

ABSTRACT

Infant outcomes after maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well described. In a prospective US registry of 263 infants, maternal SARS-CoV-2 status was not associated with birth weight, difficulty breathing, apnea, or upper or lower respiratory infection through 8 weeks of age.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Premature Birth , Female , Humans , Infant , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome , Prospective Studies , Registries , SARS-CoV-2
7.
Am J Perinatol ; 38(6): 622-631, 2021 05.
Article in English | MEDLINE | ID: covidwho-1135708

ABSTRACT

OBJECTIVE: There is a paucity of evidence to guide the clinical care of late preterm and term neonates born to women with perinatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The objective of this case series is to describe early neonatal outcomes and inpatient management in U.S. hospitals. STUDY DESIGN: We solicited cases of mother-infant dyads affected by novel coronavirus disease 2019 (COVID-19) from the Better Outcomes through Research for Newborns (BORN) Network members. Using a structured case template, participating sites contributed deidentified, retrospective birth hospitalization data for neonates ≥35 weeks of gestation at birth with mothers who tested positive for SARS-CoV-2 before delivery. We describe demographic and clinical characteristics, clinical management, and neonatal outcomes. RESULTS: Sixteen U.S. hospitals contributed 70 cases. Birth hospitalizations were uncomplicated for 66 (94%) neonates in which 4 (6%) required admission to a neonatal intensive care unit. None required evaluation or treatment for infection, and all who were tested for SARS-CoV-2 were negative (n = 57). Half of the dyads were colocated (n = 34) and 40% directly breastfed (n = 28). Outpatient follow-up data were available for 13 neonates, all of whom remained asymptomatic. CONCLUSION: In this multisite case series of 70 neonates born to women with SARS-CoV-2 infection, clinical outcomes were overall good, and there were no documented neonatal SARS-CoV-2 infections. Clinical management was largely inconsistent with contemporaneous U.S. COVID-19 guidelines for nursery care, suggesting concerns about the acceptability and feasibility of those recommendations. Longitudinal studies are urgently needed to assess the benefits and harms of current practices to inform evidence-based clinical care and aid shared decision-making. KEY POINTS: · Birth hospitalizations were uncomplicated for late preterm and term infants with maternal COVID-19.. · Nursery management of dyads affected by COVID-19 varied between hospitals.. · Adherence to contemporaneous U.S. clinical guidelines for nursery care was low.. · Breastfeeding rates were lower for dyads roomed separately than those who were colocated..


Subject(s)
Breast Feeding , COVID-19 , Hospitalization/statistics & numerical data , Pregnancy Complications, Infectious , Premature Birth/epidemiology , Term Birth , Adult , Breast Feeding/methods , Breast Feeding/statistics & numerical data , COVID-19/epidemiology , COVID-19/therapy , Female , Gestational Age , Guideline Adherence , Health Services Needs and Demand , Humans , Infant, Newborn , Infant, Premature , Intensive Care Units, Neonatal/statistics & numerical data , Male , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , Pregnancy Outcome/epidemiology , United States/epidemiology
8.
Obstet Gynecol ; 136(6): 1117-1125, 2020 12.
Article in English | MEDLINE | ID: covidwho-1020290

ABSTRACT

OBJECTIVE: To describe the clinical presentation, symptomology, and disease course of coronavirus disease 2019 (COVID-19) in pregnancy. METHODS: The PRIORITY (Pregnancy CoRonavIrus Outcomes RegIsTrY) study is an ongoing nationwide prospective cohort study of people in the United States who are pregnant or up to 6 weeks postpregnancy with known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed the clinical presentation and disease course of COVID-19 in participants who tested positive for SARS-CoV-2 infection and reported symptoms at the time of testing. RESULTS: Of 991 participants enrolled from March 22, 2020, until July 10, 2020, 736 had symptoms of COVID-19 at the time of testing; 594 tested positive for SARS-CoV-2 infection and 142 tested negative in this symptomatic group. Mean age was 31.3 years (SD 5.1), and 37% will nulliparous. Ninety-five percent were outpatients. Participants who tested positive for SARS-CoV-2-infection were a geographically diverse cohort: 34% from the Northeast, 25% from the West, 21% from the South, and 18% from the Midwest. Thirty-one percent of study participants were Latina, and 9% were Black. The average gestational age at enrollment was 24.1 weeks, and 13% of participants were enrolled after pregnancy. The most prevalent first symptoms in the cohort of patients who tested positive for SARS-CoV-2 infection were cough (20%), sore throat (16%), body aches (12%), and fever (12%). Median time to symptom resolution was 37 days (95% CI 35-39). One quarter (25%) of participants who tested positive for SARS-CoV-2 infection had persistent symptoms 8 or more weeks after symptom onset. CONCLUSION: COVID-19 has a prolonged and nonspecific disease course during pregnancy and in the 6 weeks after pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04323839.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Pregnancy Complications, Infectious/epidemiology , Adult , Betacoronavirus , COVID-19 , Coronavirus Infections/diagnosis , Female , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/virology , Prospective Studies , Risk Factors , SARS-CoV-2 , Symptom Assessment , United States/epidemiology , Young Adult
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