Human Milk and COVID-19: Insights into Colostrum Composition and Immune Benefits


Human milk is renowned for its pivotal role in providing essential nutrients and bioactive compounds that facilitate the development and overall health of newborns.

Beyond its nutritional value, human milk is a reservoir of bioactive components that confer protection against infections and contribute to the development of the infant’s immune system [29].

These bioactive substances, primarily proteins, are particularly concentrated in colostrum, the milk produced during the initial lactation moments.

Notably, changes in the composition of human milk, triggered by infections in either the mother or the infant, reflect the health status of both and offer the nursing infant defense against diseases related to intestinal and respiratory infections [30][31][32].

However, with the emergence of the COVID-19 pandemic, mothers grappling with this disease have expressed heightened concerns about breastfeeding safety.

Addressing this concern, the primary objective of a recent study was to scrutinize the presence of the SARS-CoV-2 virus in colostrum samples.

The results of the study, based on RT-qPCR analysis, demonstrated that colostrum samples from mothers with active COVID-19 infections tested negative for the virus, thus alleviating the apprehension of viral transmission through breast milk.

To date, only a handful of studies have investigated the presence of SARS-CoV-2 in colostrum [14][33][34][35][36][37], with minimal instances of viral RNA detection in samples, potentially attributed to sampling contamination through breast skin contact or the absence of mask usage during sampling [38].

The second objective of the study was to employ a novel method, the sequential window acquisition of all theoretical fragment ion spectra-MS (SWATH-MS), to characterize the protein profile of colostrum collected from mothers with COVID-19, those who had recovered post-infection, and non-infected donors.

This innovative approach allowed for the identification of 301 abundant proteins across all colostrum samples. Many of the proteins identified had been previously reported in colostrum, such as complement factors, haptoglobin, lipoprotein lipase, mucins, osteopontin, and lactoferrin [39][40].

The outcomes of the study revealed an altered milk proteome in patients with active COVID-19 infections when compared to a control group.

These findings corroborated earlier research that utilized principal component analysis (PCA) to establish distinctions in colostrum proteomes between COVID-19 patients and a control group. Moreover, comparisons of serum proteins from COVID-19 patients using uniform manifold approximation and projection (UMAP) exhibited varying degrees of separation between different patient groups [41].

Notably, this study was the first to assess the proteome of colostrum from recovered mothers, indicating a persistent alteration in the colostrum proteome in these individuals as well.

In terms of protein enrichment analysis, the study found that COVID-19 colostrum exhibited 30 enriched gene ontology (GO) terms. Proteins associated with the extracellular space and vesicles were notably heightened in COVID-19 samples, suggesting substantial secretion of these proteins.

Exosomes, which play a vital role in infant immune development, were identified as facilitators of immune benefits in the colostrum. Additionally, proteins linked to leukocyte-mediated immunity, humoral immunity, and platelet activity were upregulated, which might relate to thrombotic events observed in COVID-19 patients [42][43][44].

Examination of differentially expressed colostrum proteins revealed noteworthy interactions, such as those involving proteins A2M, GAPDH, GC, and HP, which have roles in protease inhibition, protein transport, and macrophage activation.

Of particular interest was the observation of altered immune-related proteins and protein trafficking. Immunoglobulin A (IgA), a critical component of human milk and colostrum, was found to be overexpressed in COVID-19 colostrum, along with proteins associated with leukocyte recruitment, immune modulation, and cytokine regulation.

These findings align with previous research that has shown changes in these proteins’ concentrations in response to COVID-19. Moreover, several proteins involved in lipid metabolism, cytoskeletal function, and inflammatory response were found to be altered in COVID-19 colostrum. In contrast, certain proteins related to neutrophil degranulation and immune response were downregulated.

Interestingly, the protein kappa casein (CSN3), essential for lactation, was significantly reduced in COVID-19 colostrum, potentially impacting the expression of other milk proteins. Likewise, changes in proteins like CD14 suggested possible alterations in innate immunity and immune cell recruitment.

Additionally, the protein sex hormone-binding globulin (SHBG) was found to be downregulated in COVID-19 samples, contrary to previous reports of elevated SHBG levels in male COVID-19 patients.

These findings underscore the complexity of protein expression in response to infection and the need for comprehensive studies comparing serum and colostrum proteins.

Comparing this study to existing research, the timing of colostrum sample collection emerged as a crucial factor. The study collected samples within 20 hours of parturition, offering greater accuracy in analyzing colostrum composition compared to studies that collected samples on the third or fourth postpartum days.

Notably, the study detected a gradual normalization of colostrum composition in recovered patients, suggesting that changes observed in COVID-19 colostrum may dissipate with time.

In conclusion, this study sheds light on the alterations in colostrum composition in response to COVID-19 infection. The immune benefits of colostrum from mothers with COVID-19 suggest potential protection against the virus for neonates, akin to the immune benefits observed in human milk from HIV-affected mothers.

Although discrepancies exist in the literature regarding the impact of COVID-19 on human milk composition, these findings highlight the need for further research to uncover the precise role of these altered proteins in neonatal immune development and explore their potential application in COVID-19 treatment.

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