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

Abstract

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 platelet factor 4 (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+ 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 postvaccination (All: 6.8% [95% confidence interval (CI), 4.4-10.3]; BNT162b2: 5.6% [95% CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95% CI, 4.5% to 13.7%]). Optical densities were mostly low (between 0.5 and 1.0 units; reference range, <0.50), and none of the PF4/polyanion EIA+ samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanion EIAs can occur after severe acute respiratory syndrome coronavirus 2 vaccination with both messenger RNA- and adenoviral vector-based vaccines, but many 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.

Graphical abstract

Figure 1.

Anti-PF4/polyanion IgG in relation to the time point of vaccination (day 0) with BNT162b2 and ChAdOx1 nCoV-19. An OD of >0.5 units was considered positive (gray shaded area: reference range OD <0.5). SeCo substudy: (A-B) Sera of 111 individuals who were vaccinated twice with BNT162b2 (A); 123 individuals vaccinated once with ChAdOx1 nCoV-19 (B). (C-D) Seropositive subjects with available baseline samples vaccinated with BNT162b2 (C) and vaccinated with ChAdOx1 nCoV-19 (D). Baseline samples were taken at a median of 261 days before BNT162b2 and at a median of 169 days before ChAdOx1 nCoV-19 vaccination. (E-F) AICOVI substudy: Sera of 47 participants tested at prevaccination baseline (day 0) and at days 7 and 14 after 2 doses of BNT162b2 (first dose, day 0; second dose, day 28) (E), and 1 dose of ChAdOx1 nCoV-19 (day 0) (F). Subjects with increasing ODs after vaccination are shown by triangles.