Vertical Transmission of SARS-CoV-2 Is Rare but Immunity Is Compromised in Neonates

Most data about how COVID-19 affects pregnant women and their neonates come from case reports, small case series and systematic reviews. To fill this knowledge gap, Andrea G. Edlow, MD, MSc, an investigator in the Vincent Center for Reproductive Biology at Massachusetts General Hospital, and colleagues conducted a large prospective cohort study.

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In JAMA Open Network, they report no evidence of placental infection with the SARS-CoV-2 coronavirus or vertical transmission of the virus, but they describe the reduced transplacental transfer of anti–SARS-CoV-2 antibodies that may leave neonates and infants at risk of infection.

Study Methods

The researchers enrolled 127 pregnant adult women at Mass General and two other tertiary care hospitals in Boston between April 2 and June 13, 2020. 64 tested positive for SARS-CoV-2 and 63 did not. Infected women were followed until July 10, 2020.

Viral Load

SARS-CoV-2 viral load was measured in blood samples from 107 pregnant women (62 infected, 45 uninfected) and umbilical cord blood samples from their neonates. Viral load was also measured in respiratory samples (nasal swab, oropharyngeal swab, saliva or sputum) in 78 women (44 infected, 34 uninfected). Viral load measurements were:

• Maternal blood—no detectable viremia
• Umbilical cord blood—no detectable viremia
• Respiratory samples—11 women had a detectable viral load

Transplacental Antibody Transfer

Anti-SARS-CoV-2 antibodies were measured in 37 infected women and their neonates. They found:

• Anti–receptor binding domain immunoglobin G (anti-RBD IgG) was undetectable in 35% of infected women and 38% of neonates
• Anti-nucleocapsid IgG (anti-N IgG) was detected in 30% of infected women and 41% of their neonates

Among infected women, detectable viral load in respiratory samples was significantly associated with higher maternal anti-RBD IgG titers.

Mother-to-neonate transfer of anti–SARS-CoV-2 antibodies was significantly lower than the transfer of anti-influenza hemagglutinin A antibodies (average cord-to-maternal ratio: 0.72 for anti-RBD IgG, 0.74 for anti-N IgG, 1.44 for anti-influenza; P<0.001).

Placental Infection

Pathologic examinations of 44 placentas from infected women revealed no cases of SARS-CoV-2 RNA.

Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2)—entry receptors for SARS-CoV-2—were noted in the placenta, but they were not located together and TMPRSS2 expression was low.

Applying the Findings to the Clinic

The pattern of receptor distribution and the lack of viremia may explain why neonates appear to be protected against vertical transmission. However, it is certainly possible that reduced transplacental transfer of anti–SARS-CoV-2 antibodies increases the subsequent risk of COVID-19 for neonates and infants. As of July 25, 2020, infants 0 to 2 months old comprised nearly 20% of all COVID-19 cases among children aged 0 to 18 years, according to Morbidity and Mortality Weekly Report.

The findings from this new study should immediately inform the care of pregnant women and may eventually inform vaccination protocols as well.

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