Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2

Thiele, Thomas; Ulm, Lena; Holtfreter, Silva; Schönborn, Linda; Kuhn, Sven Olaf; Scheer, Christian; Warkentin, Theodore E.; Bröker, Barbara M.; Becker, Karsten; Aurich, Konstanze; Selleng, Kathleen; Hübner, Nils-Olaf; Greinacher, Andreas

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. Wedeterminedthe frequency of anti-PF4/polyanionantibodies in healthy vaccinees andassessed whether PF4/polyanionEIA-positive sera exhibit platelet-activating propertiesafter vaccination with ChAdOx1 nCoV-19 (n=138) orBNT162b2 (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/polyanionEIA-positive samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanionEIAs 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 commonlyfollowing vaccination.