Table 3.

Studies that evaluated the impact of severe acute respiratory syndrome coronavirus 2 infection as well as maternal vaccination on immunoglobulin G , immunoglobulin M, and immunoglobulin A antibody concentrations and the impact of severe acute respiratory syndrome coronavirus 2 infection on breast milk

Author	Study Description
Flannery et al,46 2021	1471 mother/newborn dyads were studied to assess the association between maternal and neonatal SARS-CoV-2–specific antibody concentrations. SARS-CoV-2 IgG and/or IgM antibodies were detected in 83 of 1471 women (6%) at the time of delivery, and IgG was detected in cord blood from 72 of 83 newborns (87%). IgM was not detected in any cord blood specimen, and antibodies were not detected in any infant born to a seronegative mother. Placental transfer ratios >1.0 were observed among women with asymptomatic SARS-CoV-2 infections as well as those with mild, moderate, and severe COVID-19. Cord blood antibody concentrations correlated with maternal antibody concentrations and with duration between onset of infection and delivery. The findings indicate the potential for maternally derived SARS-CoV-2–specific antibodies to provide neonatal protection from coronavirus disease 2019.
Perl et al,47 2021	Study included 84 breastfeeding mothers who provided 504 breast milk samples in Israel. All participants received 2 doses of the Pfizer-BioNTech vaccine 21 d apart. Breast milk samples were collected before administration of the vaccine and then once weekly for 6 wk starting at week 2 after the first dose. Robust secretion of SARS-CoV-2–specific IgA and IgG antibodies was found in breast milk for 6 wk after vaccination. IgA secretion was evident as early as 2 wk after the first vaccine when 61.8% of samples tested positive, increasing to 86.1% at week 4 (1 wk after the second vaccine). Anti–SARS-CoV-2–specific IgG antibodies remained low for the first 3 wk, which increased to 91.7% of samples tested positive at week 4, increasing to 97% at weeks 5 and 6. Antibodies found in breast milk showed strong neutralizing effects, suggesting a potential protective effect against infection in the infant.
Collier et al,48 2021	This was an evaluation of the immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern. This prospective cohort study enrolled 103 women (30 pregnant, 16 lactating, and 57 neither pregnant nor lactating) who received a COVID-19 vaccine and 28 women (22 pregnant and 6 nonpregnant unvaccinated) with confirmed SARS-CoV-2 infection. The women received either the mRNA-1273 (Moderna) or the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines. After the second vaccine dose, fever was reported in 4 pregnant women (14%), 7 lactating women (44%), and 27 nonpregnant women (52%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in all the women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants. COVID-19 mRNA vaccine administration was immunogenic in pregnant women, and vaccine-elicited antibodies were transferred to infant cord blood and breast milk. Importantly, pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern.
Prabhu et al,49 2021	This was an evaluation of the impact of mRNA vaccine administered to 122 pregnant women of whom 55 had received one and 67 who received both vaccine doses. This included 85 who received the Pfizer-BioNTech vaccine, and 37 who received the Moderna vaccine. All women tested negative for SARS-CoV-2 infection using RT-PCR on NP swabs; all women and neonates were asymptomatic at birth and until time of discharge. Of the women tested at birth, 87 (71%) produced an IgG response, 19 (16%) produced both IgM and IgG response, and 16 (13%) had no detectable antibody response; the latter were within 4 wk of initial vaccine dose. The number of women who mounted an antibody response and conferred passive immunity to their neonates increased as a function of the number of weeks elapsed. All women and cord blood samples, except for one, had detectable IgG antibodies by 4 wk after the first vaccine dose. The earliest detection of antibodies in women occurred 5 d postvaccine dose 1, and the earliest detection of antibodies in cord blood occurred 16 d postvaccine dose 1. Forty-four percent of cord blood samples from women who received only 1 vaccine dose had detectable IgG, whereas 99% from women who received both vaccine doses had detectable IgG in cord blood. Maternal IgG levels increased significantly week by week, starting 2 wk after the first vaccine dose as well as between the first and second weeks after the second vaccine dose. Maternal IgG levels were linearly correlated with cord blood IgG levels (r = 0.50, P<.0001).
Chambers et al,50 2020	This was a study of women who tested positive by RT-PCR tests to determine whether there is transmission of infectious virus to the infant through breast milk. Breast milk samples were self-collected and mailed to the study center. In some cases, women also provided stored samples collected before enrollment. Only women who tested positive by RT-PCR tests were included. In addition, conditions of Holder pasteurization commonly used in human milk banks were mimicked by adding SARS-CoV-2 (200 × median tissue culture infectious dose 50%) to breast milk samples from 2 different control donors who provided milk samples before the onset of the pandemic. There were 18 women who provided between 1 and 12 samples, with a total of 64 samples collected at varying time points before and after the positive SARS-CoV-2 RT-PCR test result. All but 1 woman had symptomatic disease. One breast milk sample had detectable SARS-CoV-2 RNA. The positive sample was collected on the day of symptom onset; however, an additional sample taken 2 d before symptom onset and 2 samples collected 12 and 41 d later tested negative for viral RNA. The breastfed infant was not tested. No replication-competent virus was detectable in any sample, including the sample that tested positive for viral RNA. Following Holder pasteurization, viral RNA was not detected by RT-PCR in the 2 samples that had been spiked with replication-competent SARS-CoV-2, nor was culturable virus detected. However, virus was detected by culture in nonpasteurized aliquots of the same 2 milk-virus mixtures. These findings are reassuring given the known benefits of breastfeeding and human milk provided through milk banks.