Differential pre-pandemic IgA reactivity against SARS-CoV-2 and circulating human coronaviruses measured in milk collected in Uganda and the USA

Objective Uganda, like other African countries, has registered fewer COVID-19 cases and deaths per capita than non-African countries. The lower numbers of cases and deaths in Uganda might be due to pre-existing cross-immunity induced by zoonotic coronaviruses or circulating common cold human coronaviruses (HCoVs) before the COVID-19 pandemic. In order to test this premise, we compared IgA reactivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HCoVs in breast milk of US and rural Ugandan mothers collected in 2018 before the COVID-19 epidemic. Ugandan and US pre-pandemic breast milk samples were run in duplicate on enzyme-linked immunoadsorbent assay (ELISA) to measure specific IgA antibody reactivity to the spike proteins of SARS-CoV-2, human coronaviruses (HCoV) NL63, OC43, HKU1, and 229E. Pooled plasma from US COVID-19 positive and negative cases were employed as positive and negative controls, respectively. One Ugandan pre-pandemic milk sample had remarkably high reactivity against all HCoVs and SARS-CoV-2 spike proteins. There was higher IgA reactivity against the betacoronavirus HCoV-OC43 in Ugandan pre-pandemic milk samples by comparison with US pre-pandemic milk samples (p = 0.018). By contrast, there was significantly higher IgA reactivity against the alphacoronaviruses HCoV-229E and HCoV-NL63 in US pre-pandemic milk samples by comparison with Ugandan pre-pandemic milk samples (p < 0.0001 and 0.035, respectively). Conclusion Some Ugandan mothers may have robust pre-existing immunity against SARS-CoV-2 due to cross-immunity induced by HCoVs which may be passed on to their infants via breastfeeding. The differential pre-pandemic reactivity of US mothers to HCoV 229E and HCoV NL63 may have contributed to suboptimal antibody responses to SARS-CoV-2.