The Histologic And Molecular Correlates Of Covid-19 Vaccine Induced Changes In The Skin

Abstract

Twenty two patients who had developed an adverse cutaneous reaction to the Moderna or Pfizer vaccine underwent biopsies. Each case was assessed light microscopically and in select biopsies spike glycoprotein and cytokine assessment were also conducted. The patients developed self-limited cutaneous reactions often described clinically as urticarial or eczematous within one day to 4 weeks after receiving the first or second dose of the Pfizer or Moderna vaccine. Classic clinical and morphologic depictions of type IV cutaneous hypersensitivity with features of dermatitis, interface dermatitis, granulomatous inflammation and/or lymphocytic vasculitic component were observed. Clinical and/or histologic features of perniosis, pityriasis rosea, pityriasis rubra pilaris and guttate psoriasis were seen in select cases. In two cases the dominant picture was urticarial vasculitis, possibly reflective of an Arthus type III immune complex action. The biopsies of normal skin post-vaccine and skin affected by the post vaccine eruption showed rare deep microvessels positive for spike glycoprotein without complement deposition contrasting with greater vascular deposition of spike protein and complement in skin biopsies from severe COVID-19 patients. It is concluded that self-limited hypersensitivity reactions to the vaccine occur possibly due to a substance found in the vaccine vehicle such as polyethylene glycol. An immune response that is directed against human-manufactured spike has to be considered since some of the reactions clinically and or histologically closely resemble mild COVID-19. Finally, vaccine associated immune enhancement largely attributable to the adjuvant properties of the vaccine may unmask certain inflammatory milieus operational in psoriasis, atopic dermatitis and subclinical hypersensitivity.