No link between type I interferon autoantibody positivity and adverse reactions to COVID-19 vaccines

Abstract

Type I interferons act as gatekeepers against viral infection, and autoantibodies that neutralize these signaling molecules have been associated with COVID-19 severity and adverse reactions to the live-attenuated yellow fever vaccine. On this background, we sought to examine whether autoantibodies against type I interferons were associated with adverse events following COVID-19 vaccination. Our nationwide analysis suggests that type I interferon autoantibodies were not associated with adverse events after mRNA or viral-vector COVID-19 vaccines.

Fig. 1. Heatmap and scatterplot visualization of autoantibodies against type I interferons in the study groups.

Heatmap (a) illustrates autoantibody levels against type I interferons in all individuals. Color and color intensity show antibody response from the assay as described by the key. Clustering has been disabled for both rows and columns. The APS1 group shows elevated autoantibody levels for almost all examined antigens, barring IFNE and IFNK. This consistent increase in autoantibodies against multiple type I interferons is not observed in neither the BD nor the AEFI groups. Scatterplots (b) are used to compare antibody levels between the APS1 (n = 19), BD (n = 106) and AEFI (n = 290) groups, with respect to the type of vaccine for the AEFI group. The dashed lines in the scatterplots for interferons represent the threshold for ‘elevated response’ (1500 AUs). Boxplots were used to summarize data (median, 1st–3rd quartiles, whiskers represent 1.5X of interquartile range where applicable). The Y-axis has been kept constant throughout the scatterplot matrix to improve visibility and enable comparative assessment. When the three groups were compared in terms of antibody levels (Kruskal-Wallis test), it was found that the APS1 group had significantly higher values compared to the BD and AEFI groups for all analyses involving type I IFN antibodies (Bonferroni-corrected p = 0.001 for IFNK values in APS1 versus AEFI. Bonferroni-corrected p < 0.001 for all other pairwise comparisons). APS1 autoimmune polyendocrine syndrome type 1, BD blood donors, AEFI adverse events following immunization, AU arbitrary unit, IFN interferon, IgG immunoglobulin G, EBNA1 Epstein-Barr virus nuclear antigen 1, S protein spike protein, RBD receptor binding domain, N protein nucleocapsid protein, MACE major adverse cardiac event.