Methods
A prospective cohort study was conducted at the National Cheng Kung
University Hospital (NCKUH), a medical center in Southern Taiwan,
between June 6, 2022 and September 20, 2022. Eligible participants
included the following: pregnant women who delivered at the NCKUH; women
with or without a primary SARS-CoV-2 infection officially reported to
the Central Epidemic Command Center (CECC) of Taiwan; women with cord
blood sample available upon delivery and maternal blood sample available
within three days from delivery; and participants who provided informed
consent. Our study population did not have a second SARS-CoV-2
infection.
The participants were categorized based on the timing of their last
vaccination, including during the third trimester (T3), second trimester
(T2), and before and during the first trimester (T1). The diagnosis of
SARS-CoV-2 was confirmed by real-time polymerase chain reaction (RT-PCR)
or antigen testing of respiratory tract specimens, according to the
guidelines of the CECC of Taiwan. The study was approved by the
Institutional Review Board of NCKUH (IRB: B-ER-111-164), and all the
participants provided informed consent.
Clinical and laboratory data were collected using questionnaires and
electronic medical records. Cord blood was obtained from the umbilical
cord immediately after delivery. Blood samples were centrifuged at 1000
g for 10 min at room temperature, and plasma samples were aliquoted into
dedicated pre-coded tubes and stored at –80°C until analysis.
Serological Testing
Severe acute respiratory syndrome coronavirus 2 antibody levels were
measured in the maternal and fetal cord plasma using the Elecsys
Anti-SARS-CoV-2 and Anti-SARS-CoV-2 S kits (Roche Diagnostics,
Switzerland). Immunoglobulin M and G antibodies against the nucleocapsid
(anti-N) and receptor-binding domain of the spike (anti-S) of SARS-CoV-2
were detected. The cut-off for positivity was ≥1.0 or the anti-N assay
and ≥0.8 U/mL for the anti-S_RBD assay. The value of the anti-S_RBD
assay between 0.4–250 U/mL
represents the linear range, and samples >250 U/mL were
diluted with a Diluent Universal provided by the kit. The
cPassTM surrogate virus neutralization test (GenScript
Biotech Corp., USA) was conducted to measure neutralizing antibody (nAb)
titers against different SARS-CoV-2 variants. Ninety-six-well plates
coated with recombinant hACE2 and recombinant S-RBD from Wuhan and
Omicron BA.2 variants were used in the experiments, according to the
manufacturer’s instructions. An inhibition percentage ≥30% was
considered seropositive for SARS-CoV-2 nAbs. Additionally, the percent
inhibition of the Wuhan strain was converted to IU/mL using a previously
proposed formula.(18)