Figure legends:
Figure 1: Structure of SARS-CoV-2 Virus with its typical capsid and the spikes, “corona”.
ssRNA=single stranded RNA; ACE2=Angiotensin receptor 2; TMPRSS2=transmembrane protease serine subtype 2.
Figure 2: Symptoms of COVID-19.
Figure 3: Cascade of events in lung epithelium during SARS-CoV-2 infection. SARS-CoV-2 infects lung epithelial cells via ACE2 and TMPRSS2 receptor, the host cells undergo apoptosis in consequence of virus replication and release and the undergoing cell releases damage-associated molecular patterns, which induce the production of pro-inflammatory mediators by epithel and endothel cells in the neighbourhood. Inflammatory cells such as monocytes, macrophages, and T cells are recruited from the blood to the lung epithel, increase the production of inflammatory mediates and further infiltration of the lung by inflammatory cells, leading to damage of the lung structure and a “cytokine storm”, which reaches the vasculature and other organs.
ssRNA=single stranded RNA; ACE2=Angiotensin receptor 2; TMPRSS2=transmembrane protease serine subtype 2; Mo=monocyte, T=T lymphocyte, M=macrophage.
Figure 4 A: Typical skin lesions (vesicular eruptions occurring early during COVID-19 (A), with symptoms of COVID-19, i.e. maculopapular exanthema (B), urticarial rash (C), vasculitis (D) and later during COVID-19 disease Chilblain eruptions (E).
Figure 5: Immunologic features in the skin of virus-induced maculopapular exanthema (A) with virus antibody activation and interaction with immune cells in the blood, recruitment of activated cells to the skin, extravasation of erythrocytes through the blood vessels,, cytokine production and keratinocyte apoptosis and related changes to the dermis and epidermis and drug-induced maculopapular rush type IVb (B) and IVc (C) derived by activated T cells, extravasation of erythrocytes, perivascular infiltrates and perforin and granzyme B and Th1 cytokines as well as different chemokines and recruitment of T cells and eosinophils to the dermis and respective changes to the dermis and epidermis; DC=dendritic cell; B=B cell; Mo=monocyte, Eo=Eosinophil.
Figure 6: Histologic features of skin biopsies taken from two SARS-CoV-2 positive patients with maculo-papular eruptions.
A: Skin sections showing epidermis with mild hyperkeratosis, keratinocytes with frosted glass nuclei, with intranulcular and occasionally multinucleate inclusions,
reminiscent of cytopathic damage. Dermis without edema, perivascular inflammatory infiltrate extending focally to the basal layer, causing slight vacuolate damage and
pigmentary incontinence. No eosnophils are observed
B: Histology (H&E stain) showing an inconspicous epdermis and a very subtle perivascular lymphohistiocytic infiltrate in the upper dermis with admixture of few eosinophilic granulocytes.
Figure 7: IgE-, direct- and antigen-immuncomplex-mediated mast cell activation in urticaria.
Figure 8: Vasculitis of small, medium and large vessels, with formation of antigen-immune-complexes, which accumulate within the vessels and damage of the endothel, which leads to extravasation of cells and neutrophil recruitment.
Figure 9 A: 58-year old male patient diagnosed with COVID-19 and DRESS syndrome.
B: Histology (H&E stain) showing interface changes (vacuolar degeneration of the basal layer, apoptotic keratinocytes, exocytosis of lymphocytes) as well as spongiotic changes with hyperparakeratosis. Perivascular lymphohistiocytic infiltrate with admixture of few eosinophilic granulocytes. Mild extravasation of erythrocytes.