SARS-CoV-2 spike-dependent platelet activation in COVID-19 vaccine-induced thrombocytopenia

Coronavirus disease (COVID-19) is a severe viral illness that has resulted in signi fi cant morbidity and mortality worldwide. Several vaccines have been created that can prevent disease transmission as well as disease severity and mortality. All COVID-19 vaccines use the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein as the antigenic substrate. However, serious adverse reac-tions have been reported, including more than 150 cases of thrombocytopenia after vaccination. 1 A pre-cise mechanism linking COVID-19 vaccination and severe thrombocytopenia has yet to be con fi rmed. Identifying this mechanism could facilitate the development of a diagnostic test. The serotonin release assay (SRA) is the gold standard diagnostic test for heparin-induced thrombocytopenia (HIT), 2 which is characterized by severe thrombocytopenia and a risk of thrombosis. By using the SRA, we recently showed that a subset of critically ill patients with COVID-19 tested positive for platelet-activating immune complexes. 3 Similarly, Althaus et al 4 showed that immunoglobulin G (IgG) antibodies from critically ill patients who have COVID-19 can also activate platelets and lead to thrombotic events. Here, we used a modi fi ed SRA to demonstrate spike-dependent, platelet-activating immune complexes in a patient who had vaccine-induced thrombocytopenia (VIT) after receiving the Moderna COVID-19 mRNA vaccine. Blood samples were referred to the McMaster Platelet Immunology Laboratory for seconds), international normalized ratio of 1.1 (normal, 0.8-1.3), and partial thromboplastin time of 30 seconds (normal, 22-35 seconds). The presence of a lupus anticoagulant was likely excluded, given the use of a lupus-sensitive reagent for partial thromboplastin time testing. Anti-PF4/heparin antibodies were not detected (opti-cal density [OD], 0.221) and the SRA tests, with or without heparin or exogenous PF4, were negative.