PEGylated COVID-19 vaccines and cell-cell fusion

Abstract

We read with interest the recent paper
Adverse effects of COVID-19 mRNA
vaccines: the spike hypothesis by Trougakos
et al. published in Trends in Molecular
Medicine on April 20, 2022, suggesting that
the COVID-19 vaccines based on microRNA
(mRNA) technology could trigger rare but
potentially life-threatening adverse effects
(AEs) by eliciting the expression of fulllength
spike (S) protein in human tissues
and organs. This hypothesis is in line with
our own observations and those of others,
regarding the S antigen-mediated cell-cell
fusion and potential pathology [1-3].
The SARS-CoV-2 virus is marked by the
presence of a polybasic cleavage site at the
S1/S2 junction capable of forming syncytia
by fusing host cells into multinucleated
structures. For example, minute amounts
of S2 antigen can activate the human fusion
machinery, engendering large hybrid cells
that are not reversed by the COVID-19
vaccines [4]. This may explain the reports
of rare syncytia-based AEs, including
giant cell myocarditis, documented in
some Pfizer-BioNTech and Moderna
-1273 recipients [4,5]. Moreover, the S2
protein of SARS-CoV-2 virus can activate
human endogenous retroviruses (HERVs),
especially type W, that encodes for the
physiological placental fusogen syncytin-1,
a superantigen, associated not only with
cell-cell fusion but also with the “cytokine
storm”, hyperinflammatory-type responses
[6](Figure 1).