Comprehensive Serological Profile and Specificity of Maternal and Neonatal Cord Blood SARS CoV-2 Antibodies

Abstract

Objective: To describe the profile and specificity of maternal and neonatal cord-blood antibody profile in response SARS-CoV-2 virus exposure.

Methods: This is a Prospective cohort study of delivering patients at Thomas Jefferson University Hospital from April 2020-February 2021. Primary objective was to describe unique maternal and fetal antibody epitope titers and specificity in those patients with COVID-19 history. Serologic profile assessed with a multiplex platform. Antigens used were: HA-trimer Influenza A (Hong Kong H3), spike trimers for SARS-CoV-2, SARS-CoV-1, MERS-CoV, and betacoronaviruses HKU-1 and OC43, as well as the spike N-terminal domain (NTD), spike receptor binding domain (RBD), and nucleocapsid protein (N; full length) for SARS-CoV-2.

Results: 112 maternal samples and 101 maternal and cord blood pairs were analyzed. Thirty-seven had a known history of COVID-19 (positive PCR test) in the pregnancy and of those, 17 (47%) were diagnosed with COVID-19 within 30 days of delivery. Fifteen of remaining seventy-six (20%) without a known diagnosis had positive maternal serology. For those with history of COVID-19 we identified robust IgG response in maternal blood to CoV2 nucleocapsid (N), spike (S) full-length and S (RBD) antigens with more modest responses to the S (NTD) antigen. By contrast, the maternal blood IgM response appeared more specific to S (full-length), than N, S (RBD) or S (NTD) epitopes. There were significantly higher maternal and cord blood IgG response not just to CoV2 spike (p < 10 ^-18 ), but also CoV1 spike (p < 10 ^-9 ) and MERS spike (p < 10 ^-8 ). By contrast, maternal IgM responses were more specific to CoV2 (p < 10 ^-19 ), but to a lesser degree for CoV1 (p < 10 ^-5 ), and no significant differences for MERS. Maternal and cord-blood IgG were highly correlated for both S and N (R ² = 0.96 and 0.94).

Conclusions: Placental transfer is efficient, with robust N and S responses. Both nucleocapsid and spike antibody responses should be studied for a better understanding of COVID-19 immunity. IgG antibodies are cross reactive with related CoV-1 and MERS spike epitopes while IgM, which cannot cross placenta to provide neonatal passive immunity, is more SARS CoV-2 specific. Neonatal cord blood may have significantly different fine-specificity than maternal blood, despite the high efficiency of IgG transfer.