The polyethylene-glycol (PEG)-containing Covid-19 vaccines can cause hypersensitivity
reactions (HSRs), or rarely, life-threatening anaphylaxis. A causal role of anti-PEG
antibodies (Abs) has been proposed, but not yet proven in humans. The 191 blood donors
in this study included 10 women and 5 men who displayed HSRs to Comirnaty or Spikevax
Covid-19 vaccines with 3 anaphylaxis. 118 donors had pre-vaccination anti-PEG IgG/IgM
values as measured by ELISA, of which >98% were over background regardless of age,
indicating the presence of these Abs in almost everyone. Their values varied over
2-3 orders of magnitude and displayed strong left-skewed distribution with 3-4% of
subjects having >15-30-fold higher values than the respective median. First, or booster
injections with both vaccines led to significant rises of anti-PEG IgG/IgM with >10-fold
rises in about ∼10% of Comirnaty, and all Spikevax recipients, measured at different
times after the injections. The anti-PEG Ab levels measured within 4-months after
the HSRs were significantly higher than those in nonreactors. Serial testing of plasma
(n=361 tests) showed the SARS-CoV-2 neutralization IgG to vary over a broad range,
with a trend for biphasic dose dependence on anti-PEG Abs. The highest prevalence
of anti-PEG Ab positivity in human blood reported to date represents new information
which can most easily be rationalized by daily exposure to common PEG-containing medications
and/or household items. The significantly higher, HSR-non-coincidental blood level
of anti-PEG Abs in hypersensitivity reactor vs. non-reactors, taken together with
relevant clinical and experimental data in the literature, suggest that anti-PEG Ab
supercarrier people might be at increased risk for HSRs to PEG-containing vaccines,
which themselves can induce these Abs via bystander immunogenicity. Our data also
raise the possibility that anti-PEG Abs might also contribute to the reduction of
these vaccines’ virus neutralization efficacy. Thus, screening for anti-PEG Ab supercarriers
may identify people at risk for HSRs or reduced vaccine effectiveness.
