X.R.LIM1, B.P.L.LEUNG2, C.Y.L.NG1, J.W.L.TAN1, G.Y.L.CHAN1, C.M.LOH1, G.L.X.TAN1, S.C.TAN1, S.S.M.LEE1, K.P.LEONG1, B.Y.H.THONG1
Tan Tock Seng Hospital1, Singapore Institute of Technology2
42 cases of anaphylaxis were reported to the Health Sciences Authority following vaccinations for coronavirus disease 2019 (COVID-19) with Pfizer BNT162b2 and Moderna mRNA-1273 vaccines in Singapore. We aim to determine the immunological mechanisms behind these reactions.
From January to 2 March 2021, the Tan Tock Seng Hospital Clinical Immunology Laboratory received nationwide tryptase samples for 32 patients who developed immediate hypersensitivity reactions/anaphylaxis to the BNT162b2 vaccine. Remaining serum from these samples were tested for anti-polyethylene glycol (PEG) antibodies, C3a, and cytokines. In-house immunoglobulin (Ig) IgG/IgM/IgE antibodies to whole BNT162b2 vaccine as capture antigen by ELISA methods was developed. Six participants who have not received the COVID-19 vaccine served as controls (vaccine-naive group).
IgM (16 – 272 AU/ml, vs vaccine-naive <47 AU/ml) and IgG (16 – 298 AU/ml, vs vaccine-naive <70 AU/ml) antibodies, but not IgE antibodies to Pfizer BNT162b2 vaccine were detected in all samples. Similarly, elevated levels of anti-PEG IgG (1035 – 19709 U/ml, vs vaccine-naive <265 U/ml) and IgM (1682 – 5310 U/ml, vs vaccine-naive <1011 U/ml) were detected. High levels of C3a (60.9 ± 19.5 ug/ml, mean ± SD, vs normal < 10 ug/ml) were observed in all samples, while tryptase levels were not elevated. Twelve of the 32 samples exhibited enhanced Th2 cytokine serum profile during acute reaction, with high levels of interleukin (IL)-4, IL-33 and IL-10.
Our preliminary findings suggest that anaphylaxis to mRNA vaccination are likely due to non-IgE mediated pseudoanaphylaxis via complement activation related pseudoallergy, or Th2 (high) mediated allergy.