Severe acute respiratory syndrome coronavirus 2 seroprevalence and longitudinal antibody response following natural infection in pregnancy: A prospective cohort study

Abstract

Background: Antenatal care provides unique opportunities to assess severe acute respiratory syndrome coronavirus 2 seroprevalence and antibody response duration after natural infection detected during pregnancy; transplacental antibody transfer may inform peripartum and neonatal protection. We estimated seroprevalence and durability of antibodies from natural infection (anti-nucleocapsid immunoglobulin G) among pregnant people, and evaluated transplacental transfer efficiency.

Objective and design: We conducted a cross-sectional study to measure severe acute respiratory syndrome coronavirus 2 seroprevalence, and a prospective cohort study to longitudinally measure anti-nucleocapsid immunoglobulin G responses and transplacental transfer of maternally derived anti-nucleocapsid antibodies.

Methods: We screened pregnant people for the seroprevalence study between 9 December 2020 and 19 June 2021 for anti-nucleocapsid immunoglobulin G in Seattle, Washington. We enrolled anti-nucleocapsid immunoglobulin G positive people from the seroprevalence study or identified through medical records with positive reverse transcription polymerase chain reaction or antigen positive results in a prospective cohort between 9 December 2020 and 9 August 2022.

Results: In the cross-sectional study (N = 1284), 5% (N = 65) tested severe acute respiratory syndrome coronavirus 2 anti-nucleocapsid immunoglobulin G positive, including 39 (60%) without prior positive reverse transcription polymerase chain reaction results and 42 (65%) without symptoms. In the prospective cohort study (N = 107 total; N = 65 from the seroprevalence study), 86 (N = 80%) had anti-nucleocapsid immunoglobulin G positive results during pregnancy. Among 63 participants with delivery samples and prior anti-nucleocapsid positive results, 29 (46%) were anti-nucleocapsid immunoglobulin G negative by delivery. Of 34 remaining anti-nucleocapsid immunoglobulin G positive at delivery with paired cord blood, 19 (56%) had efficient transplacental anti-nucleocapsid immunoglobulin G antibody transfer. Median time from first anti-nucleocapsid immunoglobulin G positive to below positive antibody threshold was 19 weeks and did not differ by prior positive reverse transcription polymerase chain reaction status.

Conclusions: Maternally derived severe acute respiratory syndrome coronavirus 2 antibodies to natural infection may wane before delivery. Vaccines are recommended for pregnant persons to reduce severe illness and confer protection to infants.

Keywords: SARS-CoV-2; antibody; natural infection; pregnancy; seroprevalence; transplacental transfer.

Figure 1.

Flowchart of pregnant people enrolled in prospective cohort study with a history of SARS-CoV-2 infection (from seroprevalence study or identified through the medical system) as having a prior positive RT-PCR or antigen test. IgG+ if Abbott index ⩾ 1.4 except two people with IgG+ results from the seroprevalence study not enrolled in the prospective cohort who were tested for IgG with the DiaSorin Liaison SARS-CoV-2 S1/S2 IgG assay in a commercial laboratory. ^aIgG+ includes any person with an IgG+ sample at baseline or follow-up.

Figure 2.

Time to anti-N IgG below positive threshold among pregnant people with serologic evidence of prior SARS-CoV-2 infection. (a) Time from anti-N IgG+ to anti-N IgG below positive threshold (n = 68). (b) Time from infection to anti-N IgG below positive threshold (n = 85). Anti-N IgG index below positive threshold based on Abbott index < 1.4.

Figure 3.

Abbott anti-N IgG index and timing among pregnant people with a history of SARS-CoV-2 infection among those with ⩾ 2 samples available. (a) Time since first anti-N IgG+ (n = 68). (b) Time since RT-PCR+ (or antigen +) (n = 71). (c) Time since infection (n = 81). Dashed line represents Abbott index for positive threshold (log₁₀ transformed value of 1.4). Thick line represents lowess smoother; excludes samples collected at or after SARS-CoV-2 infection. ^aFirst sample collected following reinfection with SARS-CoV-2, confirmed with subsequent RT-PCR+ or antigen positive result (n = 3).

Figure 4.

IgG index among paired maternal cord blood samples among participants with anti-N IgG positive results at delivery (n = 34 pairs). Transplacental transfer ratio (infant anti-N IgG index/maternal delivery anti-N IgG index) is ⩾ 1 for circles on or above the diagonal line (dark gray), < 1 for circles below the diagonal line (light gray); circles below the horizontal dashed line (threshold for anti-N IgG positive ⩾ 1.4) represents cord blood samples below the anti-N IgG positive threshold (light gray).