Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: prospective cohort study

Abstract

ObjectiveTo investigate maternal immunoglobulins’ (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants.DesignA prospective observational study.SettingPublic healthcare system in Santa Clara County (California, USA).ParticipantsWomen with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 2021.OutcomesSARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life.ResultsOf 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 0.66%). IgG levels significantly correlated between the maternal and cord blood (Rs=0.93, p<0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60–180 days before delivery compared with <60 days (1.2 vs 0.6, p<0.0001). Infant IgG seroreversion rates over follow-up periods of 1–4, 5–12, and 13–28 weeks were 8% (4 of 48), 12% (3 of 25), and 38% (5 of 13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to 6 months of age. Two newborns showed seroconversion at 2 weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection.ConclusionsMaternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than 2 months before delivery. Maternally derived passive immunity may persist in infants up to 6 months of life. Neonates are capable of mounting a strong antibody response to perinatal SARS-CoV-2 infection.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and early infancy

“…Additionally, no infants in our study had a fetal immune response to Spike protein as demonstrated by a negative anti-SARS-CoV-2 IgM antibody in cord blood and infant follow up samples. This further supports the lack of transfer of vaccine products, as only IgG is transferred from the mother, and IgM production would indicate an endogenous fetal immune response which has rarely been seen in natural infection with SARS-CoV-2 during pregnancy 16,[21][22][23] . This provides additional reassurance that mRNA vaccination is safe during pregnancy.…”

“…This is consistent with known persistence of maternally-derived antibodies from other vaccinations including pertussis, rubella, varicella [24][25][26] . Additionally, we have previously found persistence of anti-SARS-CoV-2 IgG antibodies in infants after natural infection up to 6 months 16 . However, the functional capability of these antibodies as compared to anti-SARS-CoV-2 vaccination-derived antibodies is unknown.…”

“…In addition to protecting the mother against severe disease, vaccination during pregnancy may protect the newborn through passive transfer of maternal immunoglobulin. SARS-CoV-2 infection and vaccination during pregnancy produces an IgG response that is transferred to the fetus [10][11][12][13][14][15][16] . Evidence of newborn protection might help address maternal concerns about adverse effects.…”

Placental deficiency during maternal SARS-CoV-2 infection

“…Furthermore, the transmission rate of SARS-CoV-2 S antibody was associated with the severity of the disease as reported by previous studies [ 15 , 28 , 29 ]. A recent cohort study including 145 mothers with SARS-CoV-2 infection indicated that the transfer rate was higher in infected women in the second trimester or women with onset of infection more than 60 days before delivery [ 30 ]. The extent to which vertical transmission of maternal acquired antibodies in response to SARS-CoV-2 infection during pregnancy is a key factor for understanding possible neonatal protection to develop efficient vaccination strategies.…”

Neonates and COVID-19: state of the art

“…Transfer ratios increase with increasing time between onset of maternal infection and delivery with maximum at 60−180 days before delivery. 52 – 55 Thus, maternal vaccination may protect the infant after an adequate interval from vaccination to delivery (of at least 4 weeks). 56 Maternally derived anti-SARS-CoV-2 IgG may persist in infants up to 6 months of life.…”