Comprehensive assessment of SARS-CoV-2-reactive antibodies in human milk to determine their potential as a COVID-19 therapeutic and as a means to prevent infection of breastfed babies

Project Summary 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 comparedto adults, approximately 10% of infants experience severe COVID-19 illness requiring advanced care, andrecently, a possible link has been reported between COVID-19 and a serious inflammatory disease recentlytermed "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 youngchildren are likely responsible for a significant amount of SARS-CoV-2 dissemination (5-7). Clearly, protectingthis population from infection remains essential. One potential mechanism of protection in babies is the passiveimmunity 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 Absmay be effective in treating COVID-19 by providing secretory (s) IgA and sIgM Abs, the major Ab componentsin milk. Abs of the s class are resistant to proteolytic degradation and likely highly functional in respiratorytissue (2, 6). Nearly all sIgA/sIgM in milk is derived from the mucosal immune system, including the respiratorytract; 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 mustbe comprehensively studied for their potential therapeutic and protective efficacy. Towards that aim, we haverecruited over 1600 lactating participants, including over 600 who have recovered from COVID-19 illness. Ourpilot 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 inmilk following infection and the long-term durability of this response; (b) Determine the neutralization capacityof these Abs; and (c) Evaluate the non-neutralizing, Fc-mediated functionality of these Abs. Thiscomprehensive research will determine if COVID19-specific Abs in milk have protective biologic functions andshould be considered as a source of therapeutic Abs. These data would provide a foundation for 'convalescentmilk Ab' efficacy studies, and have implications beyond the pandemic, serving to fill a relatively largeknowledge gap regarding human milk immunology.