SARS-CoV-2, commonly termed COVID-19 for the illness it causes, has infected >4.1 million people, including >240,000 deaths. Though COVID-19 pathology in children is believed to be relatively mild compared to adults, approximately 10% of infants experience severe COVID-19 illness requiring advanced care, and recently, a possible link has been reported between COVID-19 and a serious inflammatory disease recently termed ?Pediatric Multi-System Inflammatory Syndrome Temporally Associated with COVID-19? (1-4). Furthermore, as COVID-19 symptoms do not appear to correlate with transmissibility, infants and young children are likely responsible for a significant amount of SARS-CoV-2 dissemination (5-7). Clearly, protecting this population from infection remains essential. One potential mechanism of protection in babies is the passive immunity provided through breastfeeding by a previously-infected mother, and if the SARS-CoV-2 antibody (Ab) response in milk is potent, these Abs may be highly beneficial as a COVID-19 therapeutic. These milk Abs may be effective in treating COVID-19 by providing secretory (s) IgA and sIgM Abs, the major Ab components in milk. Abs of the s class are resistant to proteolytic degradation and likely highly functional in respiratory tissue (2, 6). Nearly all sIgA/sIgM in milk is derived from the mucosal immune system, including the respiratory tract; therefore, we should expect a SARS-CoV-2-reactive sIgA/sIgM response, though the magnitude, functionality, and durability of this response remains unknown. As such, SARS-CoV-2-reactive milk Abs must be comprehensively studied for their potential therapeutic and protective efficacy. Towards that aim, we have recruited over 1600 lactating participants, including over 600 who have recovered from COVID-19 illness. Our pilot data using 15 samples found 93% obtained post-COVID-19 contain SARS-CoV-2-reactive sIgA Abs. Based on this early evidence, our proposed project intends to: (a) Measure the SARS-CoV-2-reactive Abs in milk following infection and the long-term durability of this response; (b) Determine the neutralization capacity of these Abs; and (c) Evaluate the non-neutralizing, Fc-mediated functionality of these Abs. This comprehensive research will determine if COVID19-specific Abs in milk have protective biologic functions and should be considered as a source of therapeutic Abs. These data would provide a foundation for ?convalescent milk Ab? efficacy studies, and have implications beyond the pandemic, serving to fill a relatively large knowledge gap regarding human milk immunology.

Public Health Relevance

It is important to determine if infants and young children might be protected from COVID-19 infection by the immunity that passes to them from breastfeeding. In addition, another critical use for milk-derived antibodies could be their incorporation into hyperimmune immunoglobulin preparations for treatment of COVID- 19 infection. This proposed research aims to examine what kind of immune response is typically generated in milk after COVID-19 infection, and will evaluate the potential for breastfeeding by previously-infected mothers to prevent or mitigate infant COVID-19 infection and provide a foundation for the potential inclusion of convalescent milk Abs as a treatment for COVID-19.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI158214-01
Application #
10177618
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Stemmy, Erik J
Project Start
2020-08-14
Project End
2023-07-31
Budget Start
2020-08-14
Budget End
2021-07-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029