Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios

Abstract

IMPORTANCEMaternally derived antibodies are a key element of neonatal immunity. Understanding the dynamics of maternal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and subsequent transplacental antibody transfer can inform neonatal management as well as maternal vaccination strategies.OBJECTIVE To assess the association between maternal and neonatal SARS-CoV-2-specific antibody concentrations. DESIGN, SETTING, AND PARTICIPANTSThis cohort study took place at Pennsylvania Hospital in Philadelphia, Pennsylvania. A total of 1714 women delivered at the study site between April 9 and August 8, 2020. Maternal and cord blood sera were available for antibody measurement for 1471 mother/newborn dyads.EXPOSURES SARS-CoV-2. MAIN OUTCOMES AND MEASURESIgG and IgM antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed in combination with demographic and clinical data. RESULTSThe study cohort consisted of 1714 parturient women, with median (interquartile range) age of 32 (28-35) years, of whom 450 (26.3%) identified as Black/non-Hispanic, 879 (51.3%) as White/non-Hispanic, 203 (11.8%) as Hispanic, 126 (7.3%) as Asian, and 56 (3.3%) as other race/ethnicity. Among 1471 mother/newborn dyads for which matched sera were available, SARS-CoV-2 IgG and/or IgM antibodies were detected in 83 of 1471 women (6%; 95% CI, 5%-7%) at the time of delivery, and IgG was detected in cord blood from 72 of 83 newborns (87%; 95% CI, 78%-93%). IgM was not detected in any cord blood specimen, and antibodies were not detected in any infant born to a seronegative mother. Eleven infants born to seropositive mothers were seronegative: 5 of 11 (45%) were born to mothers with IgM antibody only, and 6 of 11 (55%) were born to mothers with significantly lower IgG concentrations compared with those found among mothers of seropositive infants. Cord blood IgG concentrations were positively correlated with maternal IgG concentrations (r = 0.886; P < .001). Placental transfer ratios more than 1.0 were observed among women with asymptomatic SARS-CoV-2 infections as well as those with mild, moderate, and severe coronavirus disease 2019. Transfer ratios increased with increasing time between onset of maternal infection and delivery. CONCLUSIONS AND RELEVANCEIn this cohort study, maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta after asymptomatic as well as symptomatic infection during pregnancy. Cord blood antibody concentrations correlated with maternal antibody concentrations and with duration between onset of infection and delivery. Our findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from coronavirus disease 2019.

Relationship between viral load, infection‐to‐delivery interval and mother‐to‐child transfer of anti‐SARS‐CoV‐2 antibodies

“…In contrast to the findings of Flannery et al . who demonstrated, based on 72 mother/newborn dyads who were seropositive at delivery, that the transfer ratio of anti‐SARS‐CoV‐2 IgG correlated positively with the interval between onset of infection and delivery 5 , we did not find a significant change in transplacental transfer ratio with increasing infection‐to‐delivery interval. Our study additionally evaluated the effect of viral load on transplacental IgG transfer and showed that, even though a high viral load leads to higher concentrations of anti‐SARS‐CoV‐2 IgG antibodies in mothers, it affects negatively the transplacental transfer of IgG to the fetuses.…”

Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: prospective cohort study

“…7 8 Another study characterised a cohort of pregnant mothers who had infections during the last 120 days of gestation and showed that transfer ratios increased with length of time from infection to delivery, with transfer ratios reached above 1.0 in the majority of mothers. 6 Taken together, these studies demonstrate that crossplacental SARS-CoV-2 IgG transfer occurs throughout gestation, and a higher transfer efficiency is achieved when infection onset is more than 2 months prior to delivery. Matching the peak IgG transplacental transfer and the peak immune response after maternal infection may result in high cord IgG.…”

“…[1][2][3][4] However, the literature on SARS-CoV-2 immunity in pregnant mothers and infants remains limited. [5][6][7][8][9] Global efforts are focused on controlling the COVID-19 pandemic through public health prevention measures and vaccination. Knowledge of neonatal immune Strengths and limitations of this study ► This study included pregnant mothers with SARS-CoV-2 infection in all three trimesters of pregnancy and provided a comprehensive understanding of maternal SARS-CoV-2 IgG transplacental transfer throughout pregnancy.…”

A case of a pregnant patient with COVID‐19 infection treated with emergency c‐section and extracorporeal membrane oxygenation

“…16 However, there is evidence that maternal IgG antibodies to SARS-CoV-2 cross the placenta and may provide neonates protection against COVID-19. 17 In our case, the neonate was immediately intubated as a paralytic infusion had been initiated before delivery to assist the mother with mechanical ventilation. The neonate was transferred to the neonatal ICU for further care and subsequently extubated after a short course of mechanical ventilation.…”