Titres and neutralising capacity of SARS-CoV-2-specific antibodies in human milk: a systematic review

Low, Jia Ming; Low, Yue Wey; Zhong, Youjia; Lee, Cheuk Yiu Charlotte; Chan, Ming; Ng, Nicholas Beng Hui; Amin, Zubair; Ng, Yvonne Peng Mei

OBJECTIVE: Synthesise evidence on production of SARS-CoV-2 antibodies in human milk of individuals who had COVID-19, and antibodies’ ability to neutralise SARS-CoV-2 infectivity. DESIGN: A systematic review of studies published from 1 December 2019 to 16 February 2021 without study design restrictions. SETTING: Data were sourced from PubMed, MEDLINE, Embase, CNKI, CINAHL and WHO COVID-19 database. Search was also performed through reviewing references of selected articles, Google Scholar and preprint servers. Studies that tested human milk for antibodies to SARS-CoV-2 were included. PATIENTS: Individuals with COVID-19 infection and human milk tested for anti-SARS-CoV-2 neutralising antibodies. MAIN OUTCOME MEASURES: The presence of neutralising antibodies in milk samples provided by individuals with COVID-19 infection. RESULTS: Individual participant data from 161 persons (14 studies) were extracted and re-pooled. Milk from 133 (82.6%) individuals demonstrated the presence of anti-SARS-CoV-2 immunoglobulin A (IgA), IgM and/or IgG. Illness severity data were available in 146 individuals; 5 (3.4%) had severe disease, 128 (87.7%) had mild disease, while 13 (8.9%) were asymptomatic. Presence of neutralising antibodies in milk from 20 (41.7%) of 48 individuals neutralised SARS-CoV-2 infectivity in vitro. Neutralising capacity of antibodies was lost after Holder pasteurisation but preserved after high-pressure pasteurisation. CONCLUSION: Human milk of lactating individuals after COVID-19 infection contains anti-SARS-CoV-2-specific IgG, IgM and/or IgA, even after mild or asymptomatic infection. Current evidence demonstrates that these antibodies can neutralise SARS-CoV-2 virus in vitro. Holder pasteurisation deactivates SARS-CoV-2-specific IgA, while high-pressure pasteurisation preserves the SARS-CoV-2-specific IgA function.