COVID-19-positive Mothers Pass on SARS-CoV-2 Antibodies, but Not Virus, to Infants

  • New research on milk from COVID-19-positive mothers supports public health guidelines that encourage continued breastfeeding during and after infection.
  • Human milk does not contain viral RNA for SARS-CoV-2 and is not a source of virus transmission.
  • Milk from mothers with COVID-19 contains antibodies that bind to and neutralize SARS-CoV-2 for several months after initial infection.
  • Research on human milk and SARS-CoV-2 increases our understanding of how viral infections influence human milk composition.

 

The pace of scientific research is usually quite slow; the time frame between applying for financial support to publishing results in scientific journals is measured in years, not months. But that was before SARS-CoV-2. The urgency to understand the who, what, why, when, and how of this novel coronavirus has accelerated the way grant money is distributed, increased scientific collaboration, and loosened requirements on when scientific papers are published online. This change of pace can clearly be seen in human milk research, resulting in a “liquid gold rush” [1] of studies focused on human milk composition and SARS-CoV-2.

The July issue of SPLASH! highlighted three SARS-CoV-2-focused human milk research projects that were just getting underway in late spring and early summer 2020. As the year comes to a close, data from these studies are already being used to answer critical questions about the composition of milk from mothers that tested positive for COVID-19.

Is Breastfeeding a Mode of Viral Transmission?

In June, the World Health Organization (WHO) issued a statement [2] to encourage mothers that tested positive for (or suspected they had) COVID-19 to continue breastfeeding. All available evidence suggested the benefits provided by breastfeeding outweighed the potential risks of viral transmission, particularly in regions that lacked access to appropriate milk alternatives.

At the time the WHO guidelines were issued, there were over 20 publications on viral RNA from SARS CoV-2 in breast milk, but nearly all of these studies suffered from methodological issues, making it difficult to say definitively if breast milk was a source of viral transmission. In response, Dr. Michelle McGuire, Director and Professor in the School of Family and Consumer Sciences at the University of Idaho, and her colleagues quickly developed and published a best practices guide for breast milk collection during an infectious disease outbreak [3]. It included optimal methods for milk collection, handling, storage, and analysis to minimize the risks of contamination, false positives, and false negatives. Then, they put their methods into practice in their own study [4, available as a preprint] enrolling nearly 50 breastfeeding mothers that tested positive for COVID-19.

“Our science supports the WHO guidelines,” explains McGuire. “We haven’t found any viral RNA in the [37] samples from 18 mothers.” A similar study [5] published online (as a preprint) in August came to almost the same conclusion. Only one out of 64 samples collected from 18 mothers had detectable viral RNA. Importantly, they demonstrated that the RNA was not infectious [5].

Being able to eliminate milk as a potential source for virus transmission was critical, but it is not the only risk from breastfeeding. To better inform public health policy, McGuire’s study wanted to understand the potential risk of transmission from the breast itself. Mothers that provided milk samples also supplied swabs of their areola taken before and after cleaning. Only 8 of the 70 swabs tested contained viral RNA, and only one (collected prior to cleaning) had conclusive evidence of SARS-CoV-2 RNA [4]. “At this point, we can’t say if the viral RNA is viable. We used all of the sample to perform PCR to identify viral RNA,” says McGuire. “But this was a really interesting finding and definitely something we are going to follow-up on.” In the meantime, their data suggest that washing the breast before nursing or pumping could reduce or eliminate any potential risk [4]. They found no viral RNA from swabs taken after washing, even from the mother who provided the swab with conclusive evidence of SARS-CoV-2 RNA.

Do Mothers with COVID-19 Pass on Antibodies to SARS-CoV-2 in Milk?

The SARS-CoV-2 virus may not pass from mother to infant in milk, but antibodies directed at the virus most definitely do. In May 2020, Dr. Rebecca Powell, Assistant Professor of Medicine and Infectious Diseases at the Icahn School of Medicine at Mount Sinai, shared the results of her lab’s preliminary study that found 80% of COVID-19-positive mothers (12 out of 15) had SARS CoV-2-reactive antibodies in their milk [6].

Now, after several more months of research and larger sample sizes, Powell can make an even more definitive statement about milk antibodies. Out of 50 milk samples, “95% generated an antibody response,” explains Powell. “And as our sample size continues to grow, this number will become even more reliable.”

Dutch researchers at the University Medical Center, Amsterdam have similar findings. Dr. Kasper Hettinga, Associate Professor in Food Sciences and Agrotechnology at Wageningen University, and colleagues found 24 of 29 mothers with confirmed cases (83%) and 6 of 9 suspected cases (67%) had SARS-CoV-2-reactive antibodies in milk [7, available as a preprint].

Powell and Hettinga both initially focused on identifying SARS-CoV-2-specific secretory immunoglobulin A (sIgA, the predominant milk antibody) in milk samples collected two months after infection. “This is when we would expect the peak antibody response,” explains Powell. But in both studies, mothers continued to send in milk samples, some up to 200 days post-infection. “Antibodies were present throughout this whole time period,” says Hettinga. “The antibody response four months after infection was the same as we saw at two months,” adds Powell. “This is different than what we see in serum, where antibodies decrease over time. The mucosal immune response seems to last much longer.”

Perhaps even more exciting is that the virus-fighting capabilities of these antibodies don’t appear to diminish over time. Hettinga and McGuire’s research groups both report that SARS-CoV-2 sIgA were able to neutralize the virus in vitro [4, 7], and Hettinga shares that “the virus neutralization was stable over time, even through samples collected 200 days after infection.”

It is not possible to say whether a stable antibody response for this long is a typical response to a viral infection. “It just hasn’t been studied that thoroughly,” says Powell. “We don’t know if this is unique to SARS-CoV-2 or how sIgA works in general in milk.” To understand how long the antibody persists, both Powell and Hettinga would like to continue to follow COVID-19-positive mothers for at least the next year, if possible.

The Science Moves Forward: Milk Research during a Pandemic

Determining how long sIgA persists in milk after infection is just one of many questions McGuire, Powell, and Hettinga hope to answer about the maternal and infant response to SARS-CoV-2, and the pandemic more broadly. “Mothers and infants have been quarantined, which is a really unique situation,” says McGuire. “What are the effects of the virus and this isolation on milk?” She suggests searching for unique features of milk collected during the pandemic using an “omics” approach (e.g., the metabolome, the lipidome, the glycome, and free amino-acid profiles).

Powell’s lab is developing a study using an animal model to investigate the in vivo neutralization capabilities of sIgA. Using hamsters (which Powell describes as “a surprisingly good animal model for studying SARS-CoV-2”) and extracted sIgA specific to SARS-CoV-2 from human milk, the team will investigate if sIgA can prevent infection in infants and whether it can be used to treat infection in adults.

Hettinga and colleagues had also planned in vivo research trials by providing severely ill elderly (human) patients with pasteurized whole milk. Unfortunately for their research program, but thankfully for the population, the number of these types of COVID-19 patients in The Netherlands has decreased dramatically since late spring.

But the science moves on, with Hettinga’s team focused on the structure and function of milk sIgA directed at SARS-CoV-2. They have already found that mothers have unique profiles in their milk sIgA antigen-binding domains, the part of the antibody that recognizes and binds to the SARS-CoV-2 virus [7]. “Individual mothers are quite stable over time in the mass of the IgA she produces, but the mass varies a lot across the mothers in the study,” explains Hettinga. Next up is determining whether this variability in mass relates to which part of the virus the antibody recognizes, to the neutralizaition ability of the antibody, or to the severity of the illness in the mother.

The answers to these questions, and those being asked by McGuire and Powell, are important for understanding the novel coronavirus, but speak to broader public health issues as well. “What we really want to know is, how does milk protect infants from airway infections,” says Hettinga. “These studies will let us test a lot of the hypotheses. Even if COVID-19 goes away, we will always have airway infections in infants so it remains an important question to understand.”

 

1. Palmquist AEL, Asiodu IV, Quinn EA. 2020. The COVID-19 liquid gold rush: critical perspectives of human milk and SARS-CoV-2 infection. American Journal of Human Biology https://doi.org/10.1002/ajhb.23481

2. WHO Statement on Breastfeeding and COVID-19: https://www.who.int/news-room/commentaries/detail/breastfeeding-and-covid-19

3. McGuire MK, Seppo A, Goga A, Buonsenso , Collado MC, Donovan SM, Muller JA, Ofman G, Monroy-Valle M, O’Connor DL, Pace RM, Van de Perre P. 2020. Best practices for human milk collection for COVID-19. Preprint (Version 1), Research. https://doi.org/10.21203/rs.3.rs-84403/v1

4. Pace RM, Williams JE, Jarvinen KM, Belfort MB, Pace CDW, Lackey KA, Gogel AC, Nguyen-Contant P, Kanagaiah P, Fitzgerald T, Ferri R, Young B, Rosen-Carole C, Diaz N, Meehan CL, Caffe B, Sangster MY, Topham D, McGuire MA Seppo A, McGuire MK. 2020. COVID-19 and human milk: SARS-CoV-2, antibodies, and neutralizing capacity. MedRxiv Preprint. https://doi.org/10.1101/2020.09.16.20196071

5. Chambers DC, Krogstad P, Betrand K, Contreras D, Bode L, Tobin N, Aldrovandi G. 2020. Evaluation of SARS-CoV-2 in breastmilk from 18 infected women. MedRxiv Preprint. https://doi.org/10.1101/2020.06.12.20127944

6. Fox A, Marino J, Amanat F, Krammer F, Hahn-Holbrook J, Zolla-Pazner, Powell RL. 2020. Evidence of a significant secretory-IgA-dominant SARS-CoV-2 immune response in human milk following recovery from COVID-19. MedRxiv Preprint. https://doi.org/10.1101/2020.05.04.20089995

7. van Keulen BJ, Romijn M, Bondt A, Dingess KA, Kontopodi E, van der Straten K, den Boer MA, Bosch BJ, Brouwer PJM, de Groot CJM, Hoek M, Li Wentao, Pajkrt D, Sanders RW, Schoonderwoerd A, Tamara S, Timmermans RAH, Vidarsson G, Stittelaar KJ, Rispens TT, Hettinga KA, van Gils MJ, Hec, AJR, van Goudoever JB. 2020. Breastmilk: a source of SARS-CoV-2 specific Ig antibodies. MedRxiv Preprint. https://doi.org/10.1101/2020.08.18.20176743

 

Contributed by
Dr. Lauren Milligan Newmark
Researcher, Science Writer