•Knowledge of the extent of COVID-19 epidemic and the level of herd immunity is urgently needed•We develop a Multiplex bead-based IgG detection tool for pathogenic human coronaviruses.•The novel assay is highly sensitive and specific.•Our novel assay is more sensitive than a commercial EIA.•We show that an immunoassay using a single antigen can lead to false positive results. Knowledge of the COVID-19 epidemic extent and the level of herd immunity is urgently needed to help manage this pandemic. We used a panel of 167 samples (77 pre-epidemic and 90 COVID-19 seroconverters) and SARS-CoV1, SARS-CoV2 and MERS-CoV Spike and/or Nucleopcapsid (NC) proteins to develop a high throughput multiplex screening assay to detect IgG antibodies in human plasma. Assay performances were determined by ROC curves analysis. A subset of the COVID-19+ samples (n = 36) were also tested by a commercial NC-based ELISA test and the results compared with those of the novel assay. On samples collected ≥14 days after symptoms onset, the accuracy of the assay is 100 % (95 % CI: 100−100) for the Spike antigen and 99.9 % (95 % CI:99.7−100) for NC. By logistic regression, we estimated that 50 % of the patients have seroconverted at 5.7 ± 1.6; 5.7 ± 1.8 and 7.9 ± 1.0 days after symptoms onset against Spike, NC or both antigens, respectively and all have seroconverted two weeks after symptoms onset. IgG titration in a subset of samples showed that early phase samples present lower IgG titers than those from later phase. IgG to SARS-CoV2 NC cross-reacted at 100 % with SARS-CoV1 NC. Twenty-nine of the 36 (80.5 %) samples tested were positive by the commercial ELISA while 31/36 (86.1 %) were positive by the novel assay. Our assay is highly sensitive and specific for the detection of IgG antibodies to SARS-CoV2 proteins, suitable for high throughput epidemiological surveys. The novel assay is more sensitive than a commercial ELISA.