Study Strengths
One of the major strengths of our study is the use of two independent
assays to confirm seroprevalence and antibody levels. The Elecsys
Anti-SARS-CoV-2 assay uses a recombinant protein representing the
nucleocapsid (N) antigen for the determination of antibodies against
SARS-CoV-2 (14). The Abbot SARS-CoV-2 IgG assay is a chemiluminescent
microparticle immunoassay (CMIA) intended for the qualitative detection
of IgG antibodies to SARS-CoV-2, which also targets the nucleocapsid
protein. Both tests enable a comprehensive determination of the immune
reaction to SARS-CoV-2 and provides reliable sensitivity and specificity
(14, 15).
Our demonstration of anti- SARS-CoV-2 IgG antibodies in five umbilical
cord samples taken in women who had confirmed evidence of infection, is
noteworthy and confirms transplacental passage of anti-SARS-CoV-2
antibodies and raises the possibility of the presence of passive
immunity.
Transplacental passage of SARS-CoV-2 RNA has not been demonstrated (16,
17, 18, 19), a finding consistent with previous experience in SARS and
MERS (20), however our demonstration of transplacental passage of IgG
antibodies could potentially play an important role in future
vaccination strategies. To date, there is limited evidence of IgG
presence in cord blood. The SARS-CoV-2 genome was detected in one
umbilical cord in a study from Lombardy Italy and IgG in one cord sample
reported from Wuhan China (7, 8).
Interestingly, IgG antibody persisted and was present in an umbilical
cord blood sample 66 days post diagnosis of maternal SARS-CoV-2
suggesting transplacental passage of antibodies even when maternal
antibodies have waned. While the maternal blood sample no longer
demonstrated the presence of antibodies, the cord blood was positive for
IgG anti SARS-CoV-2. (patient c19 31, Table 2). Transplacental migration
of IgG antibodies begin from 13 weeks and peak in the second and third
trimester (21), clearly demonstrated by studies of antenatal influenza
vaccination where cord blood antibody levels are significantly higher
when the mother is vaccinated in either trimesters 2 or 3 (23, 24) The
efficiency of IgG transfer can vary from one antigen-specificity to
another. In normal pregnancy, the transfer efficiency of IgG against
pertussis can be up to 200% whereas for group B streptococcus it is
only 70% (22). Our findings suggest high efficiency of transfer of IgG
in the novel SARS-CoV-2, however larger cohorts will be required to
substantiate these findings.
These data may help direct future antenatal vaccination programs.
Antibodies have been detected in cord bloods of up to 80% of babies
born to mothers who participated in a vaccination schedule (25).
Maternal vaccination in pregnancy can therefore enhance passive antibody
transfer as the neonatal immune system begins to mature. Knowledge of
anti-SARS-CoV-2 cord blood antibody levels could help guide any future
vaccination protocol in pregnancy.
Serological assessment of pregnant women may provide a more accurate
assessment of seroprevalence. A study from Philadelphia demonstrated a
seropositivity rate of 6.2% (80/1293) in a pregnant population. This
was considerably higher than the estimated infection rate of 1.4% in
that areas general population (27). We detected a very low prevalence
rate from RT-PCR alone (1/608, 0·16%, 95%CI 0%-0·9%). However, in
keeping with other published reports, our study of asymptomatic women
also demonstrates a very low serological prevalence SARS-CoV-2(28).
Whilst the seropositivity rate of IgM was almost three times higher than
that of IgG anti-SARS-CoV-2 antibodies (IgM =21/598, 3.51% and IgG=
10/598, 1.67%) both were low within our asymptomatic population.
An assessment of the temporal response in pregnancy suggests that IgM
antibodies persisted for up to 122 days post baseline testing (Table 1)
while IgG was no longer detectable in the majority. In other
longitudinal studies of antibodies in a non-pregnant populations, IgM
levels decreased rapidly in recovered patients (29). Our pregnant
population were asymptomatic or exhibited mild symptoms only. In
previous SARS pandemics, IgM antibodies to SARS‐CoV persist for a much
shorter period of time and detectable IgG antibodies and neutralizing
viral antibodies persisted for up to 720 days (30, 31). Overall the
longevity of the immune response to SARS-CoV-2 is unknown. In SARS-CoV-1
infected patients, 90% and 50% have been shown to maintain IgG
antibodies for two and three years respectively (32).