In a recently released study in Pediatrics, Dr. Maria Grazia Capretti and colleagues from Bologna Italy describe one-year outcomes of neonates exposed to SARS-CoV-2 during pregnancy and explore placental transfer and persistence during infancy of SARS-CoV-2 antibodies (10.1542/peds.2022-056206). This fascinating study collected information on mothers infected with SARS-CoV-2 infection during pregnancy who delivered at the authors’ institution in Bologna Italy between April 2020 and April 2021; infants were followed to 1 year of age. The study is quite remarkable in its thoroughness and thoughtfulness. During this hectic period of the pandemic there was medical confusion and many knowledge gaps regarding COVID-19 illness in pregnancy, and this exceptional study gathered prospective and comprehensive information.
For the first few months of 2020 after the study began, women were initially diagnosed with SARS-CoV-2 via antibody screening at delivery, and then in November of 2020 a history of exposure combined with a nasopharyngeal swab was used for diagnosis. Maternal illness severity and trimester of illness (when possible) were noted, and infants underwent hearing testing, cerebral and abdominal ultrasounds, and fundoscopic exam in the first 3 months of life. Antibodies to SARS-CoV-2 were gathered from both mothers and infants by 48 hours after delivery and assessed during follow up until negative. A “transplacental transfer ratio” for antibodies was calculated as the infant IgG concentration divided by maternal IgG concentration at birth. Most intriguingly, the authors specifically looked for any infants who met World Health Organization (WHO) criteria for intrauterine infection with SARS-CoV-2, which requires 1) evidence of maternal SARS-CoV-2 infection during pregnancy, 2) in utero fetal SARS-CoV-2 exposure, and 3) SARS-CoV-2 persistence or immune response in the infant. Placental cells may express the angiotensin-converting enzyme 2 receptor and transmembrane protease serine-2 so there is biological plausibility for in utero transmission.1
The results are reassuring yet open up multiple avenues for future research. Of the 2,745 infants born at the hospital of interest during the study period, 130 mothers had SARS-CoV-2 infection during pregnancy, of whom 24 had peripartum infection (2 weeks before or immediately after delivery) and were not included; thus 106 women were studied, including 100 who had antibodies done within 48 hours of delivery. One infant fulfilled WHO criteria for possible in utero transmission with both infant and maternal IgG and IgM positivity at delivery. Overall, exposed infants were well, did not have medical illness or anomalies, and thrived. Transplacentally acquired maternal antibodies (SARS-CoV-2 IgG) waned with time and were gone (in 97%) by 6 months of age, which is not surprising but may be relevant foundational data for infant vaccine trials. This article made me wonder if vertical transmission will be identified more frequently as clinicians and researchers learn more about it, and also whether the encouraging infant outcomes described here for infants whose mothers had SARS-CoV-2 during pregnancy are as representative as one hopes. I have shared just a few highlights, and there is much more to learn from this intriguing study, and I hope you will find it as thought-provoking as I did.
- Faure-Bardon V, Isnard P, Roux N, Leruez-Ville M, Molina T, Bessieres B, Ville Y. Protein expression of angiotensin-converting enzyme 2, a SARS-CoV-2-specific receptor, in fetal and placental tissues throughout gestation: new insight for perinatal counseling. Ultrasound Obstet Gynecol. 2021 Feb;57(2):242-247. doi: 10.1002/uog.22178. PMID: 32798244; PMCID: PMC7461228.