Results
Between June 6, 2022 and September 20, 2022, there were 89 women
admitted to the NCKUH Maternal Unit for delivery. Of these, 46 were
either previously diagnosed with SARS-CoV-2 infection during pregnancy
or had a positive nasopharyngeal RT-PCR test result upon admission. Of
the 46 women with SARS-CoV-2 infection, 42 had paired maternal and cord
blood samples available for the analysis. Four women without SARS-CoV-2
vaccination had negative maternal plasma anti-S antibody levels;
therefore, they were not eligible for further analysis of transplacental
antibody transfer and were excluded from the SARS-CoV-2 infection group.
Of the 89 women, 43 had no history of SARS-CoV-2 infection and had
negative nasopharyngeal RT-PCR test results upon admission with paired
maternal and cord blood samples. Six women were excluded from the
SARS-CoV-2 negative group due to reactive anti-N antibody levels, which
indicated a possible previous asymptomatic SARS-CoV-2 infection without
documentation. Ultimately, 75 maternal-cord pairs were enrolled for
analysis, including 38 pairs from the SARS-CoV-2 infection group and 37
pairs from the SARS-CoV-2 negative group (Fig. S1).
Demographic, obstetric, and clinical characteristics of the participants
are summarized in Table 1. The median ages of the participants in the
SARS-CoV-2 and SARS-CoV-2 negative group were 32.5 (IQR, 29.75–38) and
34 (IQR, 30–37), respectively. Both groups had similar profiles in
terms of body mass index (BMI), gravidity, and gestational age at birth.
Cesarean section rate was higher in the SARS-CoV-2 negative group (49%
vs. 21%, p=0.012).
Both groups had similar vaccination profiles, and all the participants
included in the analysis received a vaccine. Approximately 60% of the
patients from both groups (58% in the SARS-CoV-2 group and 60% in the
non-SARS-CoV-2 group) were fully vaccinated with a primary series plus
one booster dose. Most of the patients (58% in the SARS-CoV-2 group and
62% in the non-SARS-CoV-2 group) received various types of vaccines,
including mRNA (NT162b2, Pfizer/BioNTech, or mRNA-1273, Moderna), viral
vector (ChAdOx1 nCoV-19, Oxford-AstraZeneca), and protein subunit
(MVC-COV1901, Medigen) vaccines. The difference in median intervals from
the last vaccination to delivery was not significant with median
intervals of 125 days in the SARS-CoV-2 group and 105 days in the
non-SARS-CoV-2 group (p=0.824). (Table 1)
The participants were categorized based on the timing of their last
vaccination: during the T3, T2, and before/during the T1 (Fig. 1). The
highest concentration of maternal and cord plasma anti-S antibodies was
observed in the T3 group among all the participants (median 10627.5
U/mL, IQR 6102.75–18021.5 U/mL in maternal plasma; median 16082.5, IQR
10805.5–19823.75 U/mL in cord plasma; p<0.001 and
<0.001, respectively) (Fig. 1A). For the SARS-CoV-2 negative
pregnant women, the anti-S titer was significantly higher in the T3
group (median 10442 U/mL, IQR 9535–13033 U/mL for maternal plasma;
median 14999 U/mL, IQR 12085–19042 U/mL for cord plasma;
p<0.001 and <0.001, respectively) than in the T1
(median 578.5 U/mL, IQR 160.25–6425 U/mL for maternal plasma; median
576.1 U/mL, IQR 184–3757 U/mL for cord plasma) and T2 (median 4565
U/mL, IQR 1749–10213.25 U/mL for maternal plasma; median 6017 U/mL, IQR
3838.75–11717.25 U/mL for cord plasma) groups (p<0.001 for
maternal plasma and <0.001 for cord plasma) (Fig. 1B).
However, the significance of vaccine timing on both maternal and cord
plasma anti-S titer was diminished when comparing the SARS-CoV-2
positive T1, T2, and T3 groups (Fig. 1C), which emphases the effect of
recent infection on the anti-S titer. (Table S1)
The nAbs response at different times after the last vaccination were
similar to those of anti-S antibodies. Maximum neutralizing responses
against both the Wuhan wild-type strain and Omicron variant were found
in the maternal and cord sera of the T3 group (Fig. 1D, 1G). The
neutralizing responses of the SARS-CoV-2 vaccine against the Omicron
variant were more pronounced in the SARS-CoV-2 negative participants,
and the neutralizing responses increased significantly across the T1,
T2, and T3 groups (T3 group of cord sera with median 98.15%, IQR
98.04–98.22% for the Wuhan strain; median 88.94, IQR 79.36–91.98%
for the Omicron strain; p <0.001) (Fig. 1E, 1H). However, the
nAb response rates in both maternal and cord sera were not significant
for participants with SARS-CoV-2 infection across the T1, T2, and T3
groups (Fig. 1F, 1I). (Table S2)
The levels of maternal and cord serum anti-S antibody concentrations
increased significantly seven days after SARS-CoV-2 infection (Fig. S2)
(Table S3) and peaked around 50 days from the day of the last
vaccination (Fig 2A) or SARS-CoV-2 infection (Fig. 2B). Delayed peaks
and declines were observed in the cord sera of both groups. The anti-S
antibodies were measurable in maternal and cord sera up to one year
after the last vaccination (Fig. 2A). A delayed appearance of anti-N
antibody in cord sera was also found following SARS-CoV-2 diagnosis.
While the anti-N antibodies were detected in 5 out of the total 46
maternal serum samples within 7 days from diagnosis, a delayed response
was observed in cord serum, with a rise in anti-N antibodies not
observed until 18 days after SARS-CoV-2 diagnosis. (Figure S3)
The transplacental transfer ratio (TR), which was calculated as the cord
serum antibody concentration divided by the maternal serum antibody
concentration measured the transplacental transfer of antibodies. Time
variable was presented as the time interval from delivery to the last
antigen exposure, either the last vaccination or infection, which ever
occurred last. The TRs of anti-S from the post-infection and
non-infection groups and anti-N from the post-infection group showed a
similar linear correlation with the time variable before 100 days (Fig.
3). The TRs peaked at approximately 100 days, reaching as high as 3–4,
then plateaued at approximately 1–2 after 150 days.