Maternal and neonatal cord-blood antibody profile in response to SARS-CoV-2

Pregnant women have been discovered to be especially vulnerable to respiratory pathogens, and they are more likely to require critical care and die from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pre-term delivery, pre-eclampsia, and placental pathology are linked to SARS-CoV-2 infection.

Study: Comprehensive Serological Profile and Specificity of Maternal and Neonatal Cord Blood SARS CoV-2 Antibodies. Image Credit: Alina Troeva/ShutterstockStudy: Comprehensive Serological Profile and Specificity of Maternal and Neonatal Cord Blood SARS CoV-2 Antibodies. Image Credit: Alina Troeva/Shutterstock

Many aspects of adaptive immunity are drastically altered during pregnancy, depending on gestational age. In viral infections, such as influenza A infection, these adaptations have been investigated. Immunological adaptations in SARS-CoV2 infection during pregnancy have yet to be determined.

Several discoveries emerge from early research on coronavirus disease 2019 (COVID-19) patients: Antibody (ab) responses to CoV2-specific antigens are detectable 2-3 weeks after the onset of symptoms, and practically everyone who recovers from SARS-CoV2 infection produces ab responses with a wide range of neutralizing activity.

Many concerns remain, including the longevity of these responses, the isotype profile at various phases of infection, and the drivers of newborn passive immunity. The prevalence and timing of neonatal immunity after maternal exposure can be important factors to consider when repeating vaccination during pregnancy. As a result, research into maternal antibody transfer and fetus-derived antibodies has contributed to developing guidelines for pertussis and flu vaccination timing for maximum maternal and neonatal benefit.

These investigations did not assess the spectrum of SARS-CoV-2 antibody epitopes or cross-reactivity with related viruses, limiting the understanding of the breadth of the SARS-CoV-2 antibody response and the author’s ability to identify ideal epitopes for future research. The goal of the current research was to determine the profile and specificity of maternal serum and neonatal cord blood antibody responses to SARS-CoV-2 virus exposure in mothers.

A preprint version of the study is available on the medRxiv* server while the article undergoes peer review.

The study

Maternal samples, comprising maternal and cord blood pairs, were obtained over the study period. Thirty-six had a known history of COVID-19 during pregnancy (positive PCR test), and of those, 47% were diagnosed with COVID-19 within 30 days after delivery. Positive maternal serology (IgG or IgM to SARS172 CoV-2 spike) was found in fifteen of the remaining seventy-six patients without a confirmed diagnosis. This was reflected in positive cord blood IgG. This equates to a seroprevalence rate of 20% among study participants.

Ninety-two percent of the 36 people who had a SARS-CoV-2 infection verified by PCR had positive S-IgM (N=33), and 92% of the 182 (N=33) had positive S-IgG. The authors discovered that people diagnosed with COVID-19 have high CoV2 spike protein-specific IgM and IgG levels in their maternal blood and high IgG, but low IgM levels in their cord blood support the theory that IgM does not cross the placenta. Twenty percent (15 of 76) of people with no previous COVID-19 diagnosis were seropositive for CoV2 spike protein, consistent with serosurveillance studies.

The researchers studied maternal IgG and IgM responses to distinct coronavirus spike proteins to see if there was any cross-reactivity between coronaviruses. They discovered that subjects with past COVID-19 experience had significantly higher IgG responses to CoV2 spike, CoV1 spike, and MERS spike in maternal blood and cord blood, indicating a predominantly cross-reactive IgG response.

In contrast, it was discovered that IgM responses in maternal blood were more specific to CoV2, with patients with past COVID-19 experience having a considerably larger reaction to CoV2 (p 10-19), but a lower response to CoV1 and no significant differences for MERS.

In terms of size and epitope specificity, cord blood reactions largely resembled maternal blood responses for IgG. As expected, cord blood IgM responses were roughly 50- to 400-fold lower than their maternal blood counterparts.

Finally, a principal component analysis (PCA) plot of IgG and IgM responses to CoV2 antigens in the panel demonstrates that samples with prior COVID-19 exposure can be distinguished from samples without prior exposure and maternal samples can be distinguished from cord blood samples. For the CoV2 spike and N-terminal domain (N) antigens, the authors identified a good correlation of IgG but not IgM responses between paired maternal and cord blood samples. For both the CoV2 spike and CoV2 N antigens, a linear fit between maternal and cord blood IgG responses yields a slope of 1.01.

Implications

COVID-19 exposure in the mother is linked to a particular maternal and cord blood antibody profile, with nucleocapsid and full-length spike epitopes having the best specificity in identifying exposed vs. non-exposed individuals. The latency from exposure is related to the serologic profile.

IgG antibodies from the mother to the cord blood are transferred quite efficiently. IgG antibodies cross-react with related CoV-1 and MERS spike epitopes. In contrast, IgM antibodies, which cannot cross the placenta to provide neonatal passive immunity, are highly SARS CoV-2 specific, implying important qualitative differences between maternal and neonatal passive immunity.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Colin Lightfoot

Written by

Colin Lightfoot

Colin graduated from the University of Chester with a B.Sc. in Biomedical Science in 2020. Since completing his undergraduate degree, he worked for NHS England as an Associate Practitioner, responsible for testing inpatients for COVID-19 on admission.

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