Dynamic Changes in Antibodies and Proteome in Breast Milk of Mothers Infected with Wild-Type SARS-CoV-2 and Omicron: A Longitudinal Study

Background: Breast milk confers essential passive immunity to infants, particularly during viral pandemics. This study investigates dynamic changes in SARS-CoV-2-specific antibodies and proteome in the breast milk of mothers infected with either the wild-type or Omicron variants, addressing gaps in longitudinal dynamics and conserved or variant-specific immune responses. Methods: A prospective cohort of 22 lactating mothers infected with Omicron variant (December 2022-January 2023) was analyzed alongside a published dataset of wild-type-infected mothers (January-May 2020). Breast milk samples were collected at eight time points (1, 4, 7, 14, 21, 28, 35, 42 days post-infection) from the Omicron cohort for ELISA quantification of SARS-CoV-2-specific IgA, IgG, and IgM. Proteomic analysis was conducted for both cohorts. Results: Macronutrient composition remained stable throughout the post-infection period. SARS-CoV-2-specific IgA and IgG demonstrated biphasic kinetics, rapidly rising by day 14 (IgA: 0.03 to 0.13 ng/mL; IgG: 0.91 to 37.00 ng/mL) and plateauing through day 42. In contrast, IgM levels remained unchanged. Proteomic profiling identified 135 proteins associated with IgA/IgG dynamics, including variant-specific and conserved proteins. Conclusions: Breast milk maintains nutritional integrity while mounting robust immune responses during SARS-CoV-2 infection. These findings underscore breastfeeding as a safe and protective practice during COVID-19.