ABSTRACT
Background: We evaluated SARS-CoV-2 antibody binding and neutralization responses at delivery among pregnant persons with prior SARS-CoV-2 infection by vaccine status. Method(s): We enrolled participants with evidence of prior SARS-CoV-2 infection detected in pregnancy (anti-nucleocapsid [anti-N] IgG+ on enrollment or prior RT-PCR+ or antigen+) and followed them through delivery. Maternal delivery and cord blood samples were tested for SARS-CoV-2 binding antibodies to spike (anti-S) (from vaccination and/or infection) and anti-N (from infection only) IgG by Abbott Architect followed by neutralizing antibodies (classified as neutralizing if serum dilution inhibited infection by 50% [ND50 heat] >=20 and R2 >=0.9) if sample volume allowed. Positive IgG thresholds were Abbott index >=1.4 for anti-N and >=50 AU/mL for anti-S. Chi-squared test was used to compare differences in proportions between groups. Wilcoxon rank sum test was used to compare medians. Result(s): Among 71 participants with delivery and cord samples, median age was 33 years (interquartile range [IQR] 30-35) and median gestational age was 31.7 weeks (IQR 18.0-37.9) at enrollment in pregnancy. By delivery, 17 (24%) participants were unvaccinated, 21 (30%) were partially vaccinated or had completed a primary series, and 33 (46%) were boosted. Median time from infection (RT-PCR+ or antigen+ result) to delivery was 16.7 weeks (IQR 9.7- 24.3). At delivery, 33 (46%) of maternal (median 3.2 index) and 37 (52%) of cord samples (median 3.1 index) were anti-N IgG+. Participants with >=1 vaccine were more likely to be anti-S IgG+ than those unvaccinated (100% vs. 82%, p< 0.01), have higher median anti-S IgG+ (25,000 vs 1,019 AU/ml, p< 0.01), and have neutralizing antibodies (100% vs. 81%, p< 0.01) with higher median log10 neutralization (1:4.00 vs 1:2.41, p< 0.01) at delivery. Similarly, cord blood from participants with >=1 vaccine was more likely to be anti-S IgG+ than those unvaccinated (100% vs. 82%, p< 0.01), have higher median anti-S IgG+ (25,000 vs 1,188 AU/ml, p< 0.01), and have neutralizing antibodies (100% vs. 75%, p< 0.01) with higher median log10 neutralization (1:4.00 vs 1:2.41, p< 0.01) at delivery. Conclusion(s): Among pregnant people with prior SARS-CoV-2 infection detected during pregnancy, maternal and cord blood antibody binding and neutralization responses were higher among those receiving SARS-CoV-2 vaccination prior to delivery. (Table Presented).
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
Background. Antenatal care is a unique opportunity to assess SARS-CoV-2 seroprevalence and antibody response in pregnant people, including those with previously unknown infection. Methods. Pregnant people were screened for SARS-CoV-2 IgG during antenatal care or delivery in Seattle, Washington with Abbott Architect chemiluminescent immunoassay which provides quantitative index (positive ≥1.4). Participants with IgG+ results or identified with RT-PCR+ results via medical records were invited to enroll in a longitudinal evaluation of antibody responses. We report preliminary results of an ongoing seroprevalence and longitudinal study with planned 18-month follow-up. Results. Between September 9, 2020-May 7, 2021, we screened 1304 pregnant people;62 (4.8%) tested SARS-CoV-2 IgG+, including 28 (45%) with known prior SARS-CoV-2 infection. Among participants testing IgG+, median age was 32 years (interquartile range [IQR] 26-35) and median gestational age was 21 weeks (IQR 12-38) at screening;median IgG index was 3.2 (IQR 2.1-4.9, range 1.4-9.9), including 3.9 (IQR 2.3-5.8) among those with vs. 2.7 (IQR 1.9-4.2) among those without prior RT-PCR+ results (p=0.05 by Wilcoxon rank-sum). Of 30 longitudinal study participants enrolled, 24 tested IgG+ at baseline (75% with prior RT-PCR+ result) and 6 tested IgG- on enrollment but were identified as previously RT-PCR+ via medical records;24/30 (80%) reported previous symptoms. Of 24 participants testing IgG+ at baseline, 14 (58%) had first follow-up IgG results at median of 66 days (IQR 42-104) since initial testing, with median IgG index of 2.0 (IQR 1.0-3.8). 9/14 (64%) participants with repeat IgG testing remained IgG+ at first follow-up (≤280 days after first RT-PCR+ result for those with and ≥104 days after first IgG detection for those without prior RT-PCR+ results), while 5/14 (26%) had a negative Abbott IgG test at a median of 81 days (IQR 75-112) since initial testing. Conclusion. Nearly half of pregnant people testing SARS-CoV-2 IgG+ reported no known prior SARS-CoV-2 diagnosis or symptoms. SARS-CoV-2 IgG antibody response and durability in pregnancy has implications for maternal and neonatal protection and susceptibility and highlights potential benefits of vaccination in this population.