Development of SARS-CoV-2 specific IgG and IgA antibodies in serum and milk with different SARS-COV-2 vaccines in lactating women.

BACKGROUND: Our main objective was to determine the evolution of IgG and IgA antibodies directed against SARS-CoV-2 protein S in the blood of lactating women and in breast milk. METHODS: A cohort of 110 uninfected and vaccinated breastfeeding women was followed-up for 6 months at the Marqués de Valdecilla University Hospital, Spain, in 2020. An additional group of 23 breastfeeding mothers who had no previously documented infection and had not been vaccinated against SARS-CoV-2 were included as a control group. The antibodies in blood and breast milk and their evolution at 6 months post-vaccination were analysed. RESULTS: One hundred ten breastfeeding mothers were included; 70 women (63.6%) were vaccinated with two doses of BNT162b2, 20 women (18.2%) received two doses of mRNA-1273, and 20 women (18.2%) received a single dose of ChAdOx1-S. No evidence of differences between concentrations of antibodies was found according to the type of vaccine, with the exception of serum IgA antibodies, which was higher in women vaccinated with mRNA-1273: mean [95%CI]: 0.05 AU/mL [0.03,0.06] with mRNA-1273, 0.02 AU/mL [0.01,0.03] with BNT162b2 and 0.01 AU/mL [0.00,0.03] with ChAdOx1-S, ANOVA p value = 0.03. The lack of difference between vaccines was also found when anti-S1 specific IgG in serum and breast milk were measured. CONCLUSIONS: In lactating women vaccinated against COVID-19, anti-SARS-CoV-2 antibodies can be detected in both serum and breastmilk 6 months after receiving the second dose, although their concentrations decreased when compared with concentrations reached immediately after vaccination.

COVID-19 in pregnancy: possible mechanisms not to be discounted.

SARS-CoV-2 has infected more than 16 million people worldwide. Related complications and death from COVID-19 disease and their underlying pathophysiology are intensely investigated. Pregnant women are among the affected. Although the severity of disease in pregnancy does not appear to be increased, the effects of infection on pregnancy should not escape careful examination. The currently known receptor for the virus, ACE2, regulates the renin-angiotensin system and is increased during pregnancy. Virus-receptor interactions may have significant effects on placental function, fetal development, and maternal immunity. The manifestation of cardiovascular complications of infection produces the hypothesis that a significant effect of the virus may be its influence on the maternal vascular system. Interference with the vascular adaptations to pregnancy and the post-partum may have implications for concurrent and future pregnancies as well as for long-term cardiovascular health. We should not miss the opportunity to learn from this virus about the physiology of pregnancy.

Induction of SARS-CoV-2-Specific IgG and IgA in Serum and Milk with Different SARS-CoV-2 Vaccines in Breastfeeding Women: A Cross-Sectional Study in Northern Spain.

Breastfeeding mothers were excluded from the clinical trials conducted for vaccines against SARS-CoV-2. Since the start of the vaccination, some doubts have arisen regarding its compatibility with breastfeeding. The aim of this study was to analyse the presence of anti-SARS-CoV-2 antibodies in breast milk and serum (IgG and IgA) of vaccinated breastfeeding women. The main variables of the observational study were: adverse related events after vaccination and determination of the presence of IgG and IgA isotypes antibodies in serum and in breast milk of vaccinated women against the SARS-CoV-2 antigens. Results: 110 breastfeeding mothers were included; 70 women (63.6%) were vaccinated with two doses of BNT162b2, 20 women (18.2%) with two doses of mRNA-1273, and 20 women (18.2%) with a single dose of ChAdOx1-S. Regarding adverse reactions and vaccine safety, 38 women had no adverse reactions; 20 (18.2%) had general malaise or adenopathies; 10 (9.1%) had a headache; and 7 (6.4%) had fever. When analysing IgG antibodies, significantly higher levels of antibodies were found in serum and breast milk from mothers vaccinated with BNT162b2 or mRNA-1273 vs. ChAdOx1-S (p < 0.001 and p = 0.001, respectively). Analysing IgA antibodies, significant differences were found when comparing mean values in serum from mothers vaccinated with BNT162b2 or mRNA-1273 vs. ChAdOx1-S (0.12, 0.16, and 0.02, respectively; p < 0.001) and breast milk of mothers vaccinated when comparing BNT16b2 vs. ChAdOx1-S. All vaccinated breastfeeding mothers had serum anti-S1 IgG antibodies in response to vaccination against SARS-CoV-2, regardless of the commercial vaccine administered. Conclusions: the anti-SARS-CoV-2 vaccines were well tolerated by the mothers and the breastfed infant. In addition, breastfeeding mothers offer their infants IgA and IgG isotype antibodies directed against SARS-CoV-2 protein S in breast milk.

Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study.

BACKGROUND: Pregnant and lactating women were excluded from initial coronavirus disease 2019 vaccine trials; thus, data to guide vaccine decision making are lacking. OBJECTIVE: This study aimed to evaluate the immunogenicity and reactogenicity of coronavirus disease 2019 messenger RNA vaccination in pregnant and lactating women compared with: (1) nonpregnant controls and (2) natural coronavirus disease 2019 infection in pregnancy. STUDY DESIGN: A total of 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 nonpregnant women) were enrolled in a prospective cohort study at 2 academic medical centers. Titers of severe acute respiratory syndrome coronavirus 2 spike and receptor-binding domain immunoglobulin G, immunoglobulin A, and immunoglobulin M were quantified in participant sera (n=131) and breastmilk (n=31) at baseline, at the second vaccine dose, at 2 to 6 weeks after the second vaccine, and at delivery by Luminex. Umbilical cord sera (n=10) titers were assessed at delivery. Titers were compared with those of pregnant women 4 to 12 weeks from the natural infection (n=37) by enzyme-linked immunosorbent assay. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Postvaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed-effects model, with correction for multiple comparisons, were used to assess differences among groups. RESULTS: Vaccine-induced antibody titers were equivalent in pregnant and lactating compared with nonpregnant women (pregnant, median, 5.59; interquartile range, 4.68-5.89; lactating, median, 5.74; interquartile range, 5.06-6.22; nonpregnant, median, 5.62; interquartile range, 4.77-5.98, P=.24). All titers were significantly higher than those induced by severe acute respiratory syndrome coronavirus 2 infection during pregnancy (P<.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord than maternal sera, although this finding did not achieve statistical significance (maternal sera, median, 104.7; interquartile range, 61.2-188.2; cord sera, median, 52.3; interquartile range, 11.7-69.6; P=.05). The second vaccine dose (boost dose) increased severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G, but not immunoglobulin A, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups. CONCLUSION: Coronavirus disease 2019 messenger RNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in nonpregnant women. Vaccine-induced immune responses were statistically significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.

The coronavirus disease 2019 vaccine in pregnancy: risks, benefits, and recommendations.

The coronavirus disease 2019 has caused over 2 million deaths worldwide, with over 412,000 deaths reported in Unites States. To date, at least 57,786 pregnant women in the United States have been infected, and 71 pregnant women have died. Although pregnant women are at higher risk of severe coronavirus disease 2019-related illness, clinical trials for the available vaccines excluded pregnant and lactating women. The safety and efficacy of the vaccines for pregnant women, the fetus, and the newborn remain unknown. A review of maternal and neonatal coronavirus disease 2019 morbidity and mortality data along with perinatal vaccine safety considerations are presented to assist providers with shared decision-making regarding vaccine administration for this group, including the healthcare worker who is pregnant, lactating, or considering pregnancy. The coronavirus disease 2019 vaccine should be offered to pregnant women after discussing the lack of safety data, with preferential administration for those at highest risk of severe infection, until safety and efficacy of these novel vaccines are validated.