Durable antibody and effector memory T cell responses in breastmilk from women with SARS-CoV-2

Abstract

BackgroundGiven that only 25% of pregnant women elect to receive a COVID-19 vaccine, maternal SARS-CoV-2 infection remains an important route of conferring protective passive immunity to breastfed infants of mothers who are not vaccinated.MethodsWe enrolled 30 lactating participants between December 2020 and March 2021 who had a positive PCR-test and their first COVID-19 symptoms within the previous 21 days. Participants were asked to provide serial bilateral milk samples at 12 timepoints (~ every 3 days) over a period of 35 days. A second set of samples was collected at least four months after the beginning of the first set. Participants also were asked to provide their dried blood spots and infant stool samples. All samples were tested for receptor-binding domain (RBD)-specific immunoglobulin (Ig)A, IgG, and IgM. Milk samples were assessed for neutralizing ability against the spike protein and four SARS-CoV-2 variants: D614G, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1). Permeability of the breast epithelium was assessed by measuring the sodium to potassium ions (Na:K) in milk. Using flow cytometry, memory CD4 and CD8 T cells (CD45RO+ and CCR7+/-) and mucosal-homing CD4 and CD8 T cells (CD103+) were determined in cells from milk expressed at 35 days and at least 4 months after their first milk donation.ResultsMilk antibodies from SARS-CoV-2 positive participants neutralized the spike complex. Milk from 73, 90, and 53% of participants had binding reactivities to RBD-specific IgA, IgG, and IgM, respectively. In contrast to blood spots, which showed increased levels of IgG, but not IgA or IgM, the COVID-19 response in milk was associated with a robust IgA response. Twenty-seven percent of participants had increased breast-epithelium permeability, as indicated by Na:K ≥ 0.6. The percentage of CD45RO+CCR7- effector-memory T cells in the day ≥120 milk samples was significantly higher than day 35 samples (P< 0.05).ConclusionsAntibodies in milk from participants with recent SARS-CoV-2 infection and those who recovered can neutralize the spike complex. For the first time we show that breastmilk T cells are enriched for mucosal memory T cells, further emphasizing the passive protection against SARS-CoV-2 conferred to infants via breastmilk.

Challenges of breastfeeding during COVID-19 and baby friendly protocols adopted at a maternity health center in the northern Emirates of UAE: a comprehensive review

“…In a recently published paper, it was observed that T cells play a more significant role in controlling COVID-19 than other immune cells, and therefore along with measurement of neutralizing antibodies that are known to offer protection, it is important to know the T cell count. In a recent study, the breastmilk before and after COVID-19 infection found that there was an increase in the percentage of macrophages expressing INF-alpha and this signifies the role of macrophages as the main component in the innate immunity of the milk [ 15 ].…”

The Use of Higher Secretory Immune Response of IgG And IgA in Breast Milk and Blood as a Donor Therapy in COVID-19 Survivor Mothers

“…All mothers who had recovered from COVID-19 had antibodies in their breast milk, providing opportunities to use this as a treatment for critically ill infants or to prevent severe illness in susceptible infants. Breast milk also contained high levels of IgA antibodies, which were particularly effective against diseases attacking the respiratory tract, such as COVID-19 [7].…”

“…Further studies must compare the potency of the antibodies present in breast milk to those present in the blood. The levels of sIgA in breast milk surpassed those found in plasma, and sIgA provided substantial protection for the respiratory tract [7,20].…”

“…Furthermore, it contains immune substances, which act as a protector for babies who are passively immunized [6]. In mothers exposed to COVID-19, it contains immunity that protects babies from the virus [6,7] Breastfeeding mothers suffering from SARS-CoV-2 have been reported to have increased levels of T-cells enriched with functional mucosal memory for infant protection [8]. Based on findings, there was no evidence of SARS-CoV-2 RNA in the breast milk of individuals with SARS-CoV-2.…”

“…Breast milk is rich in secretory-type antibodies (sIgG), which can be transferred to infants through breastfeeding [10]. According to previous reports, purified antibodies also have therapeutic effect on affected adults [7]. Therefore, this study aimed to analyze the relationship between IgG and IgA levels in breast milk and blood of breastfeeding mothers who have recovered from COVID-19, as well as assess the adherence to breastfeeding protocols and other determinants.…”