Samples from households with a known index case (n = 971) were examined with MULTICOV-AB to determine whether the antibody response to endemic coronaviruses (HCoV) provides any protection against infection with SARS-CoV-2. Initial screening of the population showed that seroprevalence increases with age, although several samples were within the blank range of the HCoV assays, indicating the presence of naïve samples (a). Naïve samples were defined as those having less than one-tenth the mean antibody response (indicated by dotted line), with the majority of these samples occurring in children under the age of five. HCoV-OC43 is shown as an example, all other HCoVs can be found as Fig. S9. Boxes represent the median, 25th and 75th percentiles, while whiskers show the largest and smallest non-outlier values. Outliers were identified using upper/lower quartile ±1.5 times IQR. b Line graph showing the longitudinal response of these naïve samples from T1 to T2, with new infections in HCoV-OC43 shown in red. c Box and whisker plot showing there is no significant difference in HCoV-OC43 antibody response between SARS-CoV-2 seropositive and seronegative individuals, among either adults (blue, n = 440, p = 0.974) or children (orange, n = 436, p = 0·214). Boxes represent the median, 25th and 75th percentiles, while whiskers show the largest and smallest non-outlier values. Outliers were identified using upper/lower quartile ±1·5 times IQR. Statistical significance was calculated by Mann–Whitney-U (two-sided) with *** indicating a p value < 0·001 and ns indicating a p value > 0·05. d When comparing paired samples longitudinally within the SARS-CoV-2 seropositive subgroup, there was no increase in HCoV-OC43 S1 response in either adults (blue, n = 76) or children (orange, n = 103) following SARS-CoV-2 infection. Change in response is presented as log2-fold change from T1 to T2 and only samples with either log2-fold change greater than 1 or smaller than −1 are shown. Spearman’s rank was used to calculate the ordinal association between the change in response for HCoV-OC43 and SARS-CoV-2. The same figures for the endemic coronaviruses HCoV-NL63, HCoV-HKU1 and HCoV-229E can be found as Figs. S9, S11 and S12. HCoV human Coronavirus, MFI Median Fluorescence Intensity, S1 Spike S1 domain., S1 Spike S1.