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).