Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection

Maternal immune responses during pregnancy protect the growing fetus by clearing infection, preventing its vertical transmission, and through transplacental transfer of protective immune mediators to the fetus. How maternal immune response balances SARS-CoV-2 antiviral responses with transplacental transfer of protection to the fetus remains unclear. Our study shows that upon SARS-CoV-2 maternal infection, neutralizing antibodies (NAbs) are infrequently detected in cord blood. We uncovered that this is due to impaired IgG-NAbs placental transfer in symptomatic infection and to the predominance of maternal SARS-CoV-2 NAbs of the IgA and IgM isotypes, which are prevented from crossing the placenta. Crucially, the decision between favoring maternal antiviral response or transplacental transfer of immune protection to the fetus appears to hinge on the balance between IL-6 and IL-10 induced by SARS-CoV-2 infection, decreasing or increasing transplacental transfer of IgG-NAbs, respectively. In addition, IL-10 inversely correlates with maternal NK cell frequency. Finally, we found that ongoing infection favored perinatal transfer of maternal NK cells, highlighting a maternal sponsored mechanism to protect the newborn from horizontal transmission of infection. Our data point to an evolutionary trade-off which at once optimizes maternal viral clearance and vertical transfer of immune protection during the more susceptible perinatal period. Brief SummaryIn SARS-CoV-2 maternal infection, the balance between maternal antiviral response and transplacental transfer of cellular and humoral (NAb) protection hinges on maternal IL-6 and IL-10.