Immune Response of Neonates Born to Mothers Infected With SARS-CoV-2

Abstract

IMPORTANCEAlthough several studies have provided information on short-term clinical outcomes in children with perinatal exposure to SARS-CoV-2, data on the immune response in the first months of life among newborns exposed to the virus in utero are lacking. OBJECTIVE To characterize systemic and mucosal antibody production during the first 2 months of life among infants who were born to mothers infected with SARS-CoV-2. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study enrolled 28 pregnant women who tested positive for SARS-CoV-2 infection and who gave birth at Policlinico Umberto I in Rome, Italy, from November 2020 to May 2021, and their newborns. Maternal and neonatal systemic immune responses were investigated by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breastmilk and infant saliva 48 hours after delivery and 2 months later. EXPOSURES Maternal infection with SARS-CoV-2 in late pregnancy. MAIN OUTCOMES AND MEASURES The systemic immune response was evaluated by the detection of SARS-CoV-2 IgG and IgA antibodies and receptor binding domain-specific IgM antibodies in maternal and neonatal serum. The mucosal immune response was assessed by measuring spike-specific antibodies in breastmilk and in infant saliva, and the presence of antigenantibody spike IgA immune complexes was investigated in breastmilk samples. All antibodies were detected using an enzyme-linked immunosorbent assay. RESULTSIn total, 28 mother-infant dyads (mean [SD] maternal age, 31.8 [6.4] years; mean [SD] gestational age, 38.1 [2.3] weeks; 18 [60%] male infants) were enrolled at delivery, and 21 dyads completed the study at 2 months' follow-up. Because maternal infection was recent in all cases, transplacental transfer of virus spike-specific IgG antibodies occurred in only 1 infant. One case of potential vertical transmission and 1 case of horizontal infection were observed. Virus spike proteinspecific salivary IgA antibodies were significantly increased (P = .01) in infants fed breastmilk (0.99 arbitrary units [AU]; IQR, 0.39-1.68 AU) vs infants fed an exclusive formula diet (0.16 AU; IQR, 0.02-0.83 AU). Maternal milk contained IgA spike immune complexes at 48 hours (0.53 AU; IQR, 0.25-0.39 AU) and at 2 months (0.09 AU; IQR, 0.03-0.17 AU) and may have functioned as specific stimuli for the infant mucosal immune response. CONCLUSIONS AND RELEVANCEIn this cohort study, SARS-CoV-2 spike-specific IgA antibodies were detected in infant saliva, which may partly explain why newborns are resistant to SARS-CoV-2 infection. Mothers infected in the peripartum period appear to not only passively protect the (continued) Key Points Question What is the association of maternal SARS-CoV-2 infection with immune response in offspring in the first 2 months of life? Findings In this cohort study of 21 mothers who tested positive for SARS-CoV-2 at delivery and their 22 newborns, there was 1 case of potential motherinfant vertical virus transmission and 1...

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“…Maternal breastmilk has been more closely examined as a potential protective mechanism for infants of women who were previously infected with SARs-CoV-2 or immunized with the vaccine. Multiple studies have shown that maternal spike specific IgA targeting SARs-CoV-2 is found in breastmilk of mothers previously infected or vaccinated 100 , 101 , 102 without evidence of SARs-CoV-2 transmission. 103 Similarly, breastfed infants have been shown to have salivary IgA specific for SARs-CoV-2, which is important for stimulating the mucosal immune response.…”

“… 103 Similarly, breastfed infants have been shown to have salivary IgA specific for SARs-CoV-2, which is important for stimulating the mucosal immune response. 102 While very premature infants are not capable of initiating breastfeeding until much later in their NICU stay, expressed maternal breastmilk has been encouraged and should be used whenever possible.…”

Overview of Breastfeeding Under COVID-19 Pandemic

“…However, some believe that subclinical mastitis will lead to the destruction of the milk-blood barrier and the leakage of mRNA from the blood into milk ( 100 ). Infants having milk after vaccination have no adverse reactions within 28 days after ingestion ( 94 ), and specific antibodies can be detected in infant saliva and oral mucosa ( 11 , 12 ). Therefore, after vaccination, mothers can transfer antibodies to infants to protect them from COVID-19 infection ( 101 , 102 ).…”

“…The specific antibodies against SARS-CoV-2 have been proved in breastmilk from infected or vaccinated [BNT162b2 ( 18 , 19 ), mRNA-1273 ( 19 ), ChAdOx1-S ( 20 ), CoronaVac ( 21 )] mothers ( 22 , 23 ). Interestingly, specific antibodies are also found in neonatal umbilical cord blood and saliva of breastfed infants ( 11 , 24 , 25 ), proving the antibodies could be transferred to and protect the infants without significant adverse effects, which could explain the resistance of some neonates to SARS-CoV-2 ( 12 ). Moreover, anti SARS-CoV-2 secretory immunoglobulin A (IgA) can passively protect neonates ( 5 , 12 , 22 ), while the IgA-spike antigen immune complex can also actively stimulate and strengthen the autoimmune system of newborns ( 12 ).…”

“…Interestingly, specific antibodies are also found in neonatal umbilical cord blood and saliva of breastfed infants ( 11 , 24 , 25 ), proving the antibodies could be transferred to and protect the infants without significant adverse effects, which could explain the resistance of some neonates to SARS-CoV-2 ( 12 ). Moreover, anti SARS-CoV-2 secretory immunoglobulin A (IgA) can passively protect neonates ( 5 , 12 , 22 ), while the IgA-spike antigen immune complex can also actively stimulate and strengthen the autoimmune system of newborns ( 12 ). Since there are still a few clinical trials on vaccination for lactating women and the relevant results may be associative ( 4 ), it is suggested that lactating women should receive the vaccine after considering their situation and consulting with doctors.…”