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Generalized Morphea after COVID-19 Vaccination along with Characteristic Nature of Spike Protein

Kazumi Fujioka

The previous reports suggested that Coronavirus Disease 2019 (COVID-19) may be a systemic endothelial disease or a multi-organ disease including endothliitis, hypercoagulability, and cytokine storm especially in severe type. One of the most common skin presentations associated with COVID-19 is chilblain, involving the pathogenesis of vasospasm and the type 1 interferon (IFN-1) immune response. Recent report suggested that cleaved Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike protein may exist in cutaneous endothelial cells and eccrine epithelium, showing a pathogenetic mechanism of COVID-19 endotheliitis. The mRNA COVID-19 vaccines contributed to the induced neutralizing humoral and cellular immunity, decreased infections, hospitalizations, and deaths. Meanwhile, molecular medicine indicated that the characteristic nature of the spike protein itself may cause vaccination-mediated adverse effects. In this article, current knowledge and trends of morphea after COVID-19 vaccine along with adverse effects due to the characteristic nature of spike protein have been reviewed. Recent study suggested that the prolonged presence of mRNA vaccine in lymph nodes and spike antigen in lymph nodes and blood, and the interactions between free-floating spike protein/subunits/peptide fragments and Angiotensin-Converting Enzyme 2 (ACE2) in the blood or lymph node, or ACE2 expressed in cells induced the molecular mimicry with human tissues or as an ACE2 ligand. It is supported that the IFN-1 induced by COVID-19 mRNA and adenoviral vector vaccines might contribute to induce morphea. Most patients showed the generalized morphea suggesting that the development of severe type may be attributed to the molecular mimicry along with IFN-1 immune response.