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Comparative Study
. 2022 Nov 1;5(11):e2240993.
doi: 10.1001/jamanetworkopen.2022.40993.

Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection

Dustin D Flannery  1   2   3 , Sigrid Gouma  4 , Miren B Dhudasia  1   3 , Sagori Mukhopadhyay  1   2   3 , Madeline R Pfeifer  1 , Emily C Woodford  1 , Sara M Briker  1   2 , Jourdan E Triebwasser  5 , Jeffrey S Gerber  2   3   6   7 , Jeffrey S Morris  7 , Madison E Weirick  4 , Christopher M McAllister  4 , Scott E Hensley  4 , Karen M Puopolo  1   2   3
Affiliations
Comparative Study

Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection

Dustin D Flannery et al. JAMA Netw Open. .

Abstract

Importance: Pregnant persons are at an increased risk of severe COVID-19 from SARS-CoV-2 infection, and COVID-19 vaccination is currently recommended during pregnancy.

Objective: To ascertain the association of vaccine type, time from vaccination, gestational age at delivery, and pregnancy complications with placental transfer of antibodies to SARS-CoV-2.

Design, setting, and participants: This cohort study was conducted in Pennsylvania Hospital in Philadelphia, Pennsylvania, and included births at the study site between August 9, 2020, and April 25, 2021. Maternal and cord blood serum samples were available for antibody level measurements for maternal-neonatal dyads.

Exposures: SARS-CoV-2 infection vs COVID-19 vaccination.

Main outcomes and measures: IgG antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by quantitative enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were measured after SARS-CoV-2 infection or receipt of COVID-19 vaccines.

Results: A total of 585 maternal-newborn dyads (median [IQR] maternal age, 31 [26-35] years; median [IQR] gestational age, 39 [38-40] weeks) with maternal IgG antibodies to SARS-CoV-2 detected at the time of delivery were included. IgG was detected in cord blood from 557 of 585 newborns (95.2%). Among 169 vaccinated persons without SARS-CoV-2 infection, the interval from first dose of vaccine to delivery ranged from 12 to 122 days. The geometric mean IgG level among 169 vaccine recipients was significantly higher than that measured in 408 persons after infection (33.88 [95% CI, 27.64-41.53] arbitrary U/mL vs 2.80 [95% CI, 2.50-3.13] arbitrary U/mL). Geometric mean IgG levels were higher after vaccination with the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer/BioNTech) vaccine (53.74 [95% CI, 40.49-71.33] arbitrary U/mL vs 25.45 [95% CI, 19.17-33.79] arbitrary U/mL; P < .001). Placental transfer ratios were lower after vaccination compared with after infection (0.80 [95% CI, 0.68-0.93] vs 1.06 [95% CI, 0.98-1.14]; P < .001) but were similar between the mRNA vaccines (mRNA-1273: 0.70 [95% CI, 0.55-0.90]; BNT162b2: 0.85 [95% CI, 0.69-1.06]; P = .25). Time from infection or vaccination to delivery was associated with transfer ratio in models that included gestational age at delivery and maternal hypertensive disorders, diabetes, and obesity. Placental antibody transfer was detectable as early as 26 weeks' gestation. Transfer ratio that was higher than 1.0 was present for 48 of 51 (94.1%) births at 36 weeks' gestation or later by 8 weeks after vaccination.

Conclusions and relevance: This study found that maternal and cord blood IgG antibody levels were higher after COVID-19 vaccination compared with after SARS-CoV-2 infection, with slightly lower placental transfer ratios after vaccination than after infection. The findings suggest that time from infection or vaccination to delivery was the most important factor in transfer efficiency.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Flannery reported receiving grants from the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention (CDC) outside the submitted work. Dr Mukhopadhyay reported receiving a grant from Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work. Dr Hensley reported receiving grants from the National Institute of Allergy and Infectious Diseases outside the submitted work. Dr Puopolo reported receiving grants from the National Institutes of Health and the CDC outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Flow Diagram
aIncluded 47 twin deliveries. bOne maternal-newborn dyad was excluded from analysis due to incomplete medical records. cMothers were seropositive only for IgM antibodies to SARS-CoV-2. dIncluded only the first twin from 2 sets of twins. Seropositivity in unmatched maternal or cord blood serum samples was not different from that in matched samples.
Figure 2.
Figure 2.. Association Between Placental Transfer Ratio and Time From SARS-CoV-2 Infection or First Vaccine Dose to Delivery
There was a correlation between transfer ratio and time from symptom onset or polymerase chain reaction (PCR) testing to delivery (r = 0.6885; P < .001) (A) and between transfer ratio and time from first vaccine dose to delivery among persons who received at least 1 dose of an mRNA vaccine before delivery (r = 0.8126; P < .001) (B) and among persons who received both doses of an mRNA vaccine before delivery (r = 0.8137; P < .001) (C). aOne outlier value of transfer ratio greater than 15 is not shown in the figure.
Figure 3.
Figure 3.. Heat Map of Mean Transfer Ratio by Gestational Age vs Time From SARS-CoV-2 Infection or First Vaccine Dose to Delivery
Each box displays the mean transfer ratio for the corresponding gestational age vs time from infection or first vaccine dose to delivery category among all persons contributing data (eFigure 3 in the Supplement). PCR indicates polymerase chain reaction.
See this image and copyright information in PMC

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