Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in PF4/polyanion enzyme immunoassays (EIAs) and serum-induced platelet activation is maximal in the presence of PF4. We determined the frequency of anti-PF4/polyanion antibodies in healthy vaccinees and assessed whether PF4/polyanion EIA-positive sera exhibit platelet-activating properties after vaccination with ChAdOx1 nCoV-19 (n=138) or BNT162b2 (BioNTech/Pfizer; n=143). In total, 19 of 281 participants tested positive for anti-PF4/polyanion antibodies post-vaccination (All: 6.8% [95%CI, 4.4-10.3]; BNT162b2: 5.6% [95%CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95%CI, 4.5-13.7%]). Optical densities were mostly low (between 0.5-1.0 units; reference range, <0.50) and none of the PF4/polyanion EIA-positive samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanion EIAs can occur after SARS-CoV-2 vaccination with both mRNA- and adenoviral vector-based vaccines, but the majority of these antibodies likely have minor (if any) clinical relevance. Accordingly, low-titer positive PF4/polyanion EIA results should be interpreted with caution when screening asymptomatic individuals after vaccination against Covid-19. Pathogenic platelet-activating antibodies that cause VITT do not occur commonly following vaccination.
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