SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women | Breastfeeding | JAMA | JAMA Network
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Figure.  Changes in Levels of IgA and IgG in Breast Milk Over Time
Changes in Levels of IgA and IgG in Breast Milk Over Time

A, All the comparisons between time points are P < .001. B, The comparison point at week 4 is P = .004; at week 5, P <.001; and at week 6, P = .005.

Data points represent means; error bars, 95% CIs.

Table.  Maternal and Infant Characteristics
Maternal and Infant Characteristics
1.
State of Israel Ministry of Health. The COVID-19 vaccine operation launched today. State of Israel Ministry of Health; 2021. Posted December 19, 2020. Accessed February 24, 2021. https://www.gov.il/en/Departments/news/19122020-02
2.
Polack  FP, Thomas  SJ, Kitchin  N,  et al; C4591001 Clinical Trial Group.  Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.   N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577PubMedGoogle ScholarCrossref
3.
Israel Society of Obstetrics and Gynecology. Guidelines for COVID-19 vaccination in pregnant and nursing women. Guidelines in Hebrew. Published December 20, 2020. Accessed February 24, 2021. https://govextra.gov.il/media/30093/pregnancy-covid19-vaccine.pdf
4.
Information about COVID-19 Vaccines for People who are pregnant or breastfeeding. Centers for Disease Control and Prevention. Accessed February 24, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html
5.
Pace  RM, Williams  JE, Järvinen  KM,  et al.  Characterization of SARS-CoV-2 RNA, antibodies, and neutralizing capacity in milk produced by women with COVID-19.   mBio. 2021;12(1):1-11. doi:10.1128/mBio.03192-20PubMedGoogle ScholarCrossref
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    3 Comments for this article
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    IgA
    Robert Eibl, Dr. Med. | Alumni German Cancer Research Center Association
    I found it interesting to see a robust IgA response in breast milk 2 and 4 weeks after the first vaccination into the shoulder; I wonder if there is a similar IgA response for everybody, for example in the saliva as well, which may explain the high protection and low infection rate of anyone after vaccination with Comirnaty (TM) (Pfizer/Biontech).
    CONFLICT OF INTEREST: None Reported
    IgA Antibody Against SARS-CoV-2 Variants
    Takuma Hayashi, MBBS, DMSci, GMRC, PhD. | National Hospital Organization Kyoto Medical Center
    Secretory IgA is the most abundant in the first milk secreted within the first few days after delivery. In particular, infant babies have a low ability to make IgA on their own. Therefore, IgA in breast milk is important for preventing infection with SARS-CoV-2.

    In this paper, it is found that breast milk contains a large amount of IgA and IgG against SARS-CoV-2 after the second dose of the COVID-19 vaccine. In this respect, the importance of two doses of COVID-19 vaccine was shown.

    In preliminary studies, it has already been reported that a single dose of the
    BNT162b2 vaccine markedly induces neutralized IgG activation against the B.1.1.7 variant in people previously infected with original SARS-CoV-2. However, compared to the method of antibody titers of IgM and IgG against SARS-CoV-2, the method for evaluating the antibody titer of IgA against original SARS-CoV-2 and SARS-CoV-2 variants has not yet made great progress. In particular, it is important to establish a method for evaluating the antibody titer of IgA against SARS-CoV-2 variants, which has been pointed out to have strong infectivity and a high severity rate.

    Dr. Hayashi T. and Dr. Konishi I.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Anti-Covid Antibodies in Breast Milk
    Charles Brill, MD - Retired | Thomas Jefferson University
    Will the infants' digestive enzymes break down the antibodies?
    CONFLICT OF INTEREST: None Reported
    Research Letter
    April 12, 2021

    SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women

    Author Affiliations
    • 1Pulmonary Institute, Shamir Medical Center, Zerifin, Israel
    • 2The Center for Microbiome Research, Shamir Medical Center, Zerifin, Israel
    • 3IVF Unit, Shamir Medical Center, Zerifin, Israel
    • 4Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
    • 5Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    JAMA. 2021;325(19):2013-2014. doi:10.1001/jama.2021.5782

    On December 20, 2020, Israel initiated a national vaccination program against COVID-19. One prioritized group was health care workers, many of whom are breastfeeding women.1 Despite the fact that the vaccine trial did not include this population2 and no other vaccine-related safety data had been published, breastfeeding women belonging to risk groups were encouraged to receive the vaccine.3 The Centers for Disease Control and Prevention has also recommended that breastfeeding women belonging to vaccine-target groups be immunized.4 We investigated whether maternal immunization results in secretion of SARS-CoV-2 antibodies into breast milk and evaluated any potential adverse events among women and their infants.

    Methods

    We conducted a prospective cohort study of a convenience sample of breastfeeding women (either exclusive or partial) belonging to vaccine-target groups who chose to be vaccinated. Participants were recruited from all of Israel between December 23, 2020, and January 15, 2021, through advertisements and social media. All participants received 2 doses of the Pfizer-BioNTech vaccine 21 days apart. Breast milk samples were collected before administration of the vaccine and then once weekly for 6 weeks starting at week 2 after the first dose. Samples were kept frozen pending analysis. IgG levels were detected by the Elecsys Anti–SARS-CoV-2 S serology assay and read on the Cobas e801 analyzer with a level of more than 0.8 U/mL considered positive (La Roche Ltd) and IgA with the EUROIMMUN AG Anti-SARS-CoV-2 S Kit with an extinction ratio of samples over calibrator of more than 0.8 considered positive (Supplement). At enrollment, maternal and infant demographic information was collected, followed by weekly questionnaires coupled to breast milk collection soliciting information about interim well-being and vaccine-related adverse events. The study was approved by the Shamir Medical Center Institutional Review Board; written informed consent was obtained from mothers.

    Changes in the proportion of participants with positive test results and in antibody levels during the study were evaluated using paired-sample t tests, comparing antibody levels at each point with the baseline and correcting for multiple testing using the Benjamini-Hochberg procedure. A 2-sided significance threshold was set at P < .05. Analyses were performed with R version 3.6

    Results

    Eighty-four women completed the study, providing 504 breast milk samples. Women were a mean (SD) age of 34 (4) years and infants 10.32 (7.3) months (Table).

    Mean levels of anti–SARS-CoV-2-specific IgA antibodies in the breast milk increased rapidly and were significantly elevated at 2 weeks after the first vaccine (2.05 ratio; P < .001), when 61.8% of samples tested positive, increasing to 86.1% at week 4 (1 week after the second vaccine). Mean levels remained elevated for the duration of follow-up, and at week six, 65.7% of samples tested positive. Anti–SARS-CoV-2-specific IgG antibodies remained low for the first 3 weeks, with an increase at week 4 (20.5 U/mL; P = .004), when 91.7% of samples tested positive, increasing to 97% at weeks 5 and 6 (Figure).

    No mother or infant experienced any serious adverse event during the study period. Forty-seven women (55.9%) reported a vaccine-related adverse event after the first vaccine dose and 52 (61.9%) after the second vaccine dose, with local pain being the most common complaint (Table). Four infants developed fever during the study period 7, 12, 15, and 20 days after maternal vaccination. All had symptoms of upper respiratory tract infection including cough and congestion, which resolved without treatment except for 1 infant who was admitted for neonatal fever evaluation due to his age and was treated with antibiotics pending culture results. No other adverse events were reported.

    Discussion

    This study found robust secretion of SARS-CoV-2 specific IgA and IgG antibodies in breast milk for 6 weeks after vaccination. IgA secretion was evident as early as 2 weeks after vaccination followed by a spike in IgG after 4 weeks (a week after the second vaccine). A few other studies have shown similar findings in women infected with COVID-19.5 Antibodies found in breast milk of these women showed strong neutralizing effects, suggesting a potential protective effect against infection in the infant.

    The study has limitations. First, no functional assays were performed. However, previous studies have showed neutralizing capacities of the same antibodies as measured for this study. Second, serum antibody testing or SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction testing were not performed, which would have provided interesting correlates.

    Section Editor: Jody W. Zylke, MD, Deputy Editor.
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    Article Information

    Corresponding Author: Ilan Youngster, MD, MMSc, Pediatric Infectious Diseases Unit and the Center for Microbiome Research, Shamir Medical Center, Zerifin 70300, Israel (youngsteri@shamir.gov.il).

    Accepted for Publication: March 30, 2021.

    Published Online: April 12, 2021. doi:10.1001/jama.2021.5782

    Author Contributions: Dr Youngster had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Perl and Ms Uzan-Yulzari contributed equally as co–first authors. Mr Rinott and Dr Youngster contributed equally as co–senior authors.

    Concept and design: Perl, Uzan-Yulzari, I. Youngster.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Perl, Uzan-Yulzari, Asiskovich, M. Youngster, Rinott, I. Youngster.

    Critical revision of the manuscript for important intellectual content: Klainer, M. Youngster, Rinott, I. Youngster.

    Statistical analysis: Rinott, I. Youngster.

    Administrative, technical, or material support: Perl, Uzan-Yulzari, Klainer, Asiskovich, M. Youngster.

    Supervision: Perl, Rinott, I. Youngster.

    Other: Uzan-Yulzari, Klainer.

    Conflict of Interest Disclosures: None reported.

    Additional Contributions: We thank Elkana Kohn, PhD, and Netanel Agajany, MD (both for data collection) and Dvora Stahi, MSc (for data analysis), all affiliated with Shamir Medical Center, Zerifin, Israel; none was compensated for his or her contributions.

    References
    1.
    State of Israel Ministry of Health. The COVID-19 vaccine operation launched today. State of Israel Ministry of Health; 2021. Posted December 19, 2020. Accessed February 24, 2021. https://www.gov.il/en/Departments/news/19122020-02
    2.
    Polack  FP, Thomas  SJ, Kitchin  N,  et al; C4591001 Clinical Trial Group.  Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.   N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577PubMedGoogle ScholarCrossref
    3.
    Israel Society of Obstetrics and Gynecology. Guidelines for COVID-19 vaccination in pregnant and nursing women. Guidelines in Hebrew. Published December 20, 2020. Accessed February 24, 2021. https://govextra.gov.il/media/30093/pregnancy-covid19-vaccine.pdf
    4.
    Information about COVID-19 Vaccines for People who are pregnant or breastfeeding. Centers for Disease Control and Prevention. Accessed February 24, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html
    5.
    Pace  RM, Williams  JE, Järvinen  KM,  et al.  Characterization of SARS-CoV-2 RNA, antibodies, and neutralizing capacity in milk produced by women with COVID-19.   mBio. 2021;12(1):1-11. doi:10.1128/mBio.03192-20PubMedGoogle ScholarCrossref
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