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Most pregnant women who develop COVID-19 experience mild or asymptomatic illness and rarely transmit the disease to their infants in utero or postpartum. Findings from a new study suggest that specialized “decoy” proteins in amniotic fluid and breast milk protect fetuses and newborns from severe COVID-19.

SARS-CoV-2, the virus that causes COVID-19, gains entry to cells via various receptor proteins, including angiotensin-converting enzyme 2 (ACE2), CD26, CD147, and neuropilin-1 (NRP-1), among others. These proteins are typically embedded in cellular membranes, but they can also be found in soluble form, existing freely in bodily fluids. Some evidence suggests that soluble forms of ACE2, in particular, serve as “viral traps,” or decoys, effectively preventing SARS-CoV-2 from interacting with membrane-bound forms.

The authors of the study analyzed amniotic fluid (collected at 37 weeks' gestation) and breast milk (collected at two and six weeks postpartum) that had been stored prior to the COVID-19 pandemic. They centrifuged the samples and then measured the amount of soluble ACE2, CD26, CD147, and NRP-1 present.

Their analysis revealed that all the samples contained an abundance of the soluble forms of the various proteins. Amniotic fluid contained more CD26 than breast milk, but breast milk contained higher amounts of ACE2 and NRP-1. In addition, the soluble proteins in amniotic fluid were of different isoforms (shorter) than those in breast milk. These findings suggest that soluble receptors in breast milk and amniotic fluid act as decoy receptors to reduce the risk of SARS-CoV-2 infection and/or severe COVID-19 outcomes in fetuses and infants.

Interestingly, human milk oligosaccharides (HMOs) in breast milk serve as decoys to protect the infant from gut infections. In order for pathogenic bacteria to cause infection, they must first target and bind to specific carbohydrates found on the cells that line the gut. However, the overall structure and shape of HMOs mimics that of the carbohydrate targets. The pathogens bind to the HMOs, instead, foiling their ability to establish themselves in the gut. Learn more about HMOs and other immunomodulatory aspects of breast milk in our overview article.

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