Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates

Abstract

Background: Pregnant women and their neonates represent 2 vulnerable populations with an interdependent immune system that are highly susceptible to viral infections. The immune response of pregnant women to severe acute respiratory syndrome coronavirus 2 and the interplay of how the maternal immune response affects the neonatal passive immunity have not been studied systematically.

Objective: We characterized the serologic response in pregnant women and studied how this serologic response correlates with the maternal clinical presentation and with the rate and level of passive immunity that the neonate received from the mother.

Study design: Women who gave birth and who tested positive for immunoglobulin M or immunoglobulin G against severe acute respiratory syndrome coronavirus 2 using semiquantitative detection in a New York City hospital between March 22, 2020, and May 31, 2020, were included in this study. A retrospective chart review of the cases that met the inclusion criteria was conducted to determine the presence of coronavirus disease 2019 symptoms and the use of oxygen support. Serology levels were compared between the symptomatic and asymptomatic patients using a Welch 2 sample t test. Further chart review of the same patient cohort was conducted to identify the dates of self-reported onset of coronavirus disease 2019 symptoms and the timing of the peak immunoglobulin M and immunoglobulin G antibody levels after symptom onset was visualized using local polynomial regression smoothing on log₂-scaled serologic values. To study the neonatal serology response, umbilical cord blood samples of the neonates born to the subset of serology positive pregnant women were tested for serologic antibody responses. The maternal antibody levels of serology positive vs the maternal antibody levels of serology negative neonates were compared using the Welch 2 sample t test. The relationship between the quantitative maternal and quantitative neonatal serologic data was studied using a Pearson correlation and linear regression. A multiple linear regression analysis was conducted using maternal symptoms, maternal serology levels, and maternal use of oxygen support to determine the predictors of neonatal immunoglobulin G levels.

Results: A total of 88 serology positive pregnant women were included in this study. The antibody levels were higher in symptomatic pregnant women than in asymptomatic pregnant women. Serology studies in 34 women with symptom onset data revealed that the maternal immunoglobulin M and immunoglobulin G levels peak around 15 and 30 days after the onset of coronavirus disease 2019 symptoms, respectively. Furthermore, studies of 50 neonates born to this subset of serology positive women showed that passive immunity in the form of immunoglobulin G is conferred in 78% of all neonates. The presence of passive immunity is dependent on the maternal antibody levels, and the levels of neonatal immunoglobulin G correlate with maternal immunoglobulin G levels. The maternal immunoglobulin G levels and maternal use of oxygen support were predictive of the neonatal immunoglobulin G levels.

Conclusion: We demonstrated that maternal serologies correlate with symptomatic maternal infection, and higher levels of maternal antibodies are associated with passive neonatal immunity. The maternal immunoglobulin G levels and maternal use of oxygen support, a marker of disease severity, predicted the neonatal immunoglobulin G levels. These data will further guide the screening for this uniquely linked population of mothers and their neonates and can aid in developing maternal vaccination strategies.

Keywords: COVID-19 infection; antibody levels; asymptomatic infection; baby; convalescent infection; cord blood; mother; mother-baby dyads; passive immunity; predictor; prevalence; symptomatic infection; time course.

Figure 1

IgG and IgM levels in symptomatic and asymptomatic pregnant women A comparison of the level of (A) IgG and (B) IgM serology values in asymptomatic (beige, n=51) and symptomatic (green, n=37) pregnant women. All the positive serology cutoffs were 1 (dashed line). The values are shown on a log₂ scale. IgG, immunoglobulin G; IgM, immunoglobulin M. Kubiak et al. Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates. Am J Obstet Gynecol 2021.

Figure 2

Timing of the serologic response in pregnant women The serologic results were plotted as a function of time to better understand the timing of antibody response. A, IgG (blue) and IgM (red) values for each pregnant woman plotted as a function of elapsed time from the first COVID-19 symptoms. All positive serology cutoffs were 1 (dashed line). The values are shown on a log₂ scale. Data are plotted as LOESS curves for each group. The shaded regions indicate the 95% confidence intervals derived during LOESS. IgG, immunoglobulin G; IgM, immunoglobulin M; LOESS, local polynomial regression smoothing. Kubiak et al. Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates. Am J Obstet Gynecol 2021.

Figure 3

Passive immunity and the serology levels in neonates Neonates were tested for serology to understand the rate of passive immunity and the pattern of passive immunity between the mother to child. A, The number of neonates that were serology negative (beige) vs IgG positive (purple) neonates. No neonates were IgM positive. B, The maternal IgG antibody levels grouped by those mothers who gave birth to serology positive neonates (purple, n=39) and those who gave birth to serology negative neonates (beige, n=11). C, The IgG levels of mothers vs IgG levels of neonates. All positive serology cutoffs were 1 (dashed line). Values are shown on a log₂ scale. IgG, immunoglobulin G; IgM, immunoglobulin M. Kubiak et al. Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates. Am J Obstet Gynecol 2021.