Protective role of SARS-CoV-2 anti-S IgG against breakthrough infections among European healthcare workers during pre and post-Omicron surge—ORCHESTRA project

Purpose Anti SARS-CoV-2 vaccination initially showed high effectiveness in preventing COVID-19. However, after the surge of variants of concern, the effectiveness dropped. Several studies investigated if this was related to the decrease of the humoral response over time; however, this issue is still unclear. The aim of this study was to understand whether SARS-CoV-2 anti-S IgG levels can be used to predict breakthrough infection risk and define the timing for further booster doses administration. Method Within the framework of the ORCHESTRA Project, over 20,000 health workers from 11 European centers were enrolled since December 2020. We performed two Cox proportional hazards survival analyses regarding pre-Omicron (from January to July 2021) and Omicron (December 2021–May 2022) periods. The serological response was classified as high (above the 75th percentile), medium (25th-75th), or low (