* Authors on the Steering Committee contributed equally to the oversight of the study, including study design and maintaining the quality of study conduct. CONTRIBUTORS Owen O'Connor, Barbara Pro, Tim Illidge and Lorenz Trumper formed the ECHELON-2 steering committee and contributed equally to the oversight of the study, including study design and maintaining the quality of study conduct.

Messenger RNA-based vaccines against COVID-19 induce a robust anti-SARS-CoV-2 antibody response with potent viral neutralization activity. Antibody effector functions are determined by their constant region subclasses and by their glycosylation patterns, but their role in vaccine efficacy is unclear. Moreover, whether vaccination induces antibodies similar to those in patients with COVID-19 remains unknown. We analyze BNT162b2 vaccine-induced IgG subclass distribution and Fc glycosylation patterns and their potential to drive effector function via Fcg receptors and complement pathways. We identify unique and dynamic pro-inflammatory Fc compositions that are distinct from those in patients with COVID-19 and convalescents. Vaccine-induced anti-Spike IgG is characterized by distinct Fab-and Fc-mediated functions between different age groups and in comparison to antibodies generated during natural viral infection. These data highlight the heterogeneity of Fc responses to SARS-CoV-2 infection and vaccination and suggest that they support long-lasting protection differently.

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In December 2020 the Israeli Health Ministry began a mass vaccination campaign with the BNT162b2 vaccine. This was an important step in overcoming the severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2) pandemic. Autoimmune phenomenon have been described after receiving vaccinations. Here we describe a case series of patients who developed acquired Thrombotic Thrombocytopenic Purpura, a rare autoimmune disease, within several days of receiving the BNT162b2 vaccine. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13(ADAMTS13) activity should be evaluated in patients with history of aTTP before and after any vaccination, especially the SARS‐CoV‐2 vaccination, and immunosuppression treatment should be considered before vaccination in cases of low ADAMTS13 activity. Patients should be closely monitored after the vaccine for clinical situation and laboratory data. Post vaccination thrombocytopenia assessment should include immune thrombocytopenic purpura, vaccine‐induced immune thrombotic thrombocytopenia and acquired thrombotic thrombocytopenic purpura.