The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a major threat to global health. The high mortality rate reported during the early stage of the COVID-19 pandemic resulted in panic among patients, including lactating mothers.1–3 The detection of SARS-CoV-2 RNA in breastmilk raised great concerns regarding the possibility of mother-to-child transmission (MTCT) of the virus.4 According to several reports on the presence of SARS-CoV-2 in breastmilk, some experts suggested that breastfeeding should be conducted with caution, while others recommended that, infants should be separated from their mother and breastfeeding should be discontinued.5–7
Is it necessary to adopt such strict measures for the prevention of MTCT of SARS-CoV-2? Firstly, although some studies reported the presence of SARS-CoV-2 RNA in breastmilk, others did not detect any viral RNA.4,8–10 Therefore, additional detection methods (e.g., viral protein detection) are required to confirm the presence or absence of SARS-CoV-2 in breastmilk. Secondly, even if SARS-CoV-2 RNA is detected, it is unknown whether breastmilk contains live virus. Thus far, infectious viruses have not been isolated from breastmilk, and MTCT of SARS-CoV-2 via breastmilk has not been reported.4,8 Thirdly, it is not possible to culture the infectious viral particles isolated from the breastmilk of mothers with ongoing SARS-CoV-2 infection, regardless of the detection of viral RNA in breastmilk.11,12 Therefore, there is a low probability for the presence of infectious SARS-CoV-2 particles in breastmilk. Moreover, several national and international guidelines revised their recommendations on breastfeeding and clearly stated that breastmilk is safe and could be directly used to feed infants.13–15 To avoid possible transmission via other routes, such as the respiratory tract, an expert consensus on breastfeeding in case of maternal infections suggests that infants born to mothers with influenza virus or SARS-CoV-2 can be fed with expressed breast milk without requirement for sterilization.13
Is SARS-CoV-2 infectious when mixed into the breastmilk? The presence of SARS-CoV-2 infectious viral particles in breastmilk is currently unknown. Nonetheless, there is an urgent need to investigate whether the virus remains infectious when mixed with breastmilk. Fan et al.16 reported that, although SARS-CoV-2 or pangolin coronavirus (GX_P2V) can be easily cultured in vero-E6 and Huh7.5 cells, exposure to various concentrations of human breastmilk collected prior to the emergence of COVID-19 completely blocked the infectivity of these viruses. In addition, this activity is not associated with the presence of IgA antibodies in milk. Moreover, the investigators found that lactoferrin possesses significant anti–SARS-CoV-2 activity, and whey protein isolated from breastmilk has markedly higher capacity to block the infectivity of SARS-CoV-2 compared to lactoferrin. According to the results of that study, breastmilk may contain other antiviral components that play an important role in inhibiting SARS-CoV-2 infection.
Breastmilk is rich in nutrients and various bioactive molecules, such as cytokines, growth factors, immune cells, antibodies, and other components that can inhibit different types of viral infection.17 It was reported that breastmilk has antiviral activity against various viruses, such as influenza virus, Zika virus, hepatitis B virus, human immunodeficiency virus, etc.18,19 It is well established that antibodies with specific neutralizing activity to SARS-CoV-2 are typically induced by SARS-CoV-2 infection or vaccination. Breastmilk contains high level of antibodies (e.g., IgA) after viral infection or vaccination, which is an effective approach to inhibiting SARS-CoV-2.20 In addition, other components such as lactoferrin, mucin 1 (MUC1), MUC4, and lactalbumin, have shown high antiviral activity. Interestingly, SARS-CoV-2 can also be inhibited by these components.16 Lai et al.21 revealed that lactoferrin, MUC1, and lactalbumin showed significant activity against SARS-CoV-2 and its variants. Mechanistically, these factors could inhibit viral attachment through interference with the interaction between heparan sulfate proteoglycan and viral protein, as well as block viral replication by inhibiting viral RNA-dependent RNA polymerase activity.
Based on the broad antiviral activity of human breastmilk, its components offer promise for the development of antiviral drugs in the future.22–24 The 3-hydroxyphthalic anhydride modified β-lactoglobulin LG (3HP-β-LG), an active component in anti-human papillomavirus (HPV) biological dressing (JB01-BD), has been used in clinics since 2013 to block cervical infection by HPV. Hua et al.25 reported that 3HP-β-LG via intravaginal application also showed high anti-SARS-CoV-2 activity. Hence, this component of breastmilk was successfully used as a drug to inhibit HPV. Similarly, other components (e.g., lactoferrin, MUC1, and lactalbumin) that have exhibited broad and high activity against SARS-CoV-2 and other viruses can be used to design new antiviral drugs.16,19,21 Importantly, climate change and intense globalization have created favorable conditions for viral transmission. Therefore, there is a pressing need to design drugs with broad antiviral activity for overcoming outbreaks of emerging infectious diseases. Currently, the World Health Organization has prioritized eight viral diseases (including COVID-19, Ebola, and Zika) for which research and development is urgently warranted.26 Drug development using common targets against a bundle of representative highly pathogenic viruses, particularly those that have caused epidemic in the last decades, will assist healthcare professionals in the fight against emerging viruses in the future.
Conflicts of Interest
Yi-Hua Zhou is an editorial board member of Maternal-Fetal Medicine. The article was subject to the journal’s standard procedures, with peer review handled independently of this editor and the associated research groups.
1. Davis BD, McKnight DE, Teodorescu D, et al. Quantifying depression-related language on social media during the COVID-19 pandemic. Int J Popul Data Sci 2020;5(4):1716. doi: 10.23889/ijpds.v5i4.1716.
2. Khubchandani J, Kandiah J, Saiki D. The COVID-19 pandemic, stress, and eating practices in the United States. Eur J Investig Health Psychol Educ 2020;10(4):950–956. doi: 10.3390/ejihpe10040067.
3. The Lancet. The COVID-19 pandemic in 2023: far from over. Lancet 2023;401(10371):79. doi: 10.1016/S0140-6736(23)00050-8.
4. Groß R, Conzelmann C, Müller JA, et al. Detection of SARS-CoV-2 in human breastmilk. Lancet 2020;395(10239):1757–1758. doi: 10.1016/S0140-6736(20)31181-8.
5. Perrine CG, Chiang KV, Anstey EH, et al. Implementation of hospital practices supportive of breastfeeding in the context of COVID-19—United States, July 15–August 20, 2020. MMWR Morb Mortal Wkly Rep 2020;69(47):1767–1770. Published 2020 Nov 27. doi: 10.15585/mmwr.mm6947a3.
6. Wang L, Shi Y, Xiao T, et al. Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition). Ann Transl Med 2020;8(3):47. doi: 10.21037/atm.2020.02.20.
7. Editorial Office. Fighting the novel coronavirus: the publication of the Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition). Ann Palliat Med 2020;9(2):524–525. doi: 10.21037/apm.2020.02.02.
8. Chambers C, Krogstad P, Bertrand K, et al. Evaluation for SARS-CoV-2 in breast milk from 18 infected women. JAMA 2020;324(13):1347–1348. doi: 10.1001/jama.2020.15580.
9. Zhu C, Liu W, Su H, et al. Breastfeeding risk from detectable severe acute respiratory syndrome coronavirus 2 in breastmilk. J Inf Secur 2020;81(3):452–482. doi: 10.1016/j.jinf.2020.06.001.
10. Tam PCK, Ly KM, Kernich ML, et al. Detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human breast milk of a mildly symptomatic patient with coronavirus disease 2019 (COVID-19). Clin Infect Dis 2021;72(1):128–130. doi: 10.1093/cid/ciaa673.
11. Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet 2020;395(10226):809–815. doi: 10.1016/S0140-6736(20)30360-3.
12. Costa S, Posteraro B, Marchetti S, et al. Excretion of SARS-CoV-2 in human breast milk. Clin Microbiol Infect 2020;26(10):1430–1432. doi: 10.1016/j.cmi.2020.05.027.
13. Society of Perinatal Medicine, Chinese Medical Association. Expert consensus on breastfeeding in case of maternal infections (in Chinese). Chin J Perinat Med 2021;24(7):481–489. doi: 10.3760/cma.j.cn113903-20210530-00507.
14. Pérez-Bermejo M, Peris-Ochando B, Murillo-Llorente MT. COVID-19: Relationship and impact on breastfeeding-a systematic review. Nutrients 2021;13(9):2972. doi: 10.3390/nu13092972.
15. WHO frequently asked questions: Breastfeeding and COVID-19 for health care workers. J Hum Lact 2020;36(3):392–396. doi: 10.1177/0890334420939556.
16. Fan H, Hong B, Luo Y, et al. The effect of whey protein on viral infection and replication of SARS-CoV-2 and pangolin coronavirus in vitro. Signal Transduct Target Ther 2020;5(1):275. doi: 10.1038/s41392-020-00408-z.
17. Sokou R, Konstantinidi A, Boutsikou T, et al. Breastfeeding in the era of COVID-19. A narrative review. J Obstet Gynaecol 2022;42(4):539–545. doi: 10.1080/01443615.2021.1929112.
18. Florisa R, Recio I, Berkhout B, et al. Antibacterial and antiviral effects of milk proteins and derivatives thereof. Curr Pharm Des 2003;9(16):1257–1275. doi: 10.2174/1381612033454810.
19. Luo Y, Xiang K, Liu J, et al. Inhibition of in vitro infection of hepatitis B virus by human breastmilk. Nutrients 2022;14(8):1561. doi: 10.3390/nu14081561.
20. Kelly JC, Carter EB, Raghuraman N, et al. Anti-severe acute respiratory syndrome coronavirus 2 antibodies induced in breast milk after Pfizer-BioNTech/BNT162b2 vaccination. Am J Obstet Gynecol 2021;225(1):101–103. doi: 10.1016/j.ajog.2021.03.031.
21. Lai X, Yu Y, Xian W, et al. Identified human breast milk compositions effectively inhibit SARS-CoV-2 and variants infection and replication. iScience 2022;25(4):104136. doi: 10.1016/j.isci.2022.104136.
22. Zhou YH, Luo Y, Xiang K. Thinking more about inhibition of breast Milk on the infectivity of SARS-CoV-2. JAMA Pediatr 2022;176(5):526–527. doi: 10.1001/jamapediatrics.2021.6613.
23. Chatterjee M, van Putten JPM, Strijbis K. Defensive properties of mucin glycoproteins during respiratory infections—relevance for SARS-CoV-2. MBio 2020;11(6):e02374–e02320. doi: 10.1128/mBio.02374-20.
24. Hu Y, Meng X, Zhang F, et al. The in vitro antiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor. Emerg Microbes Infect 2021;10(1):317–330. doi: 10.1080/22221751.2021.1888660.
25. Hua C, Ma Q, Zhu Y, et al. Repurposing of a clinically used anti-HPV agent to prevent and treat SARS-CoV-2 infection as an intranasal formulation. Signal Transduct Target Ther 2021;6(1):318. Published 2021 Aug 26. doi: 10.1038/s41392-021-00737-7.
26. Lu L, Su S, Yang H, et al. Antivirals with common targets against highly pathogenic viruses. Cell 2021;184(6):1604–1620. doi: 10.1016/j.cell.2021.02.013.