SARS-CoV-2-Induced Vasculitic Skin Lesions Are Associated with Massive Spike Protein Depositions in Autophagosomes.

In patients infected with severe acute respiratory syndrome coronavirus 2, vasculopathic changes of the skin are associated with a severe prognosis. However, the pathogenesis of this vasculopathy is not conclusively clarified. In this study, 25 prospectively collected skin samples from patients with COVID-19-related skin lesions were examined for vasculopathic changes and, in case of vasculitis, were further analyzed with electron microscopy and immunohistochemistry. Vasculopathy was observed in 76% of all COVID-19-related inflammatory skin lesions. Visual endothelial changes without manifest leukocytoclastic vasculitis were found in 60% of the COVID-19-related skin lesions, whereas leukocytoclastic vasculitis was diagnosed in 16%. In the cases of vasculitis, there were extensive spike protein depositions in microvascular endothelial cells that colocalized with the autophagosome proteins LC3B and LC3C. The autophagy protein complex LC3-associated endocytosis in microvascular endothelial cells seems to be an important pathogenic factor for severe acute respiratory syndrome coronavirus 2-related vasculitis in the skin. On ultrastructural morphology, the vasculitic process was dominated by intracellular vesicle formation and endothelial cell disruption. Direct presence of severe acute respiratory syndrome coronavirus 2 particles in the skin was not observed. Therefore, our results suggest that instead of direct viral infection, dermal vasculitic lesions in COVID-19 are caused by severe acute respiratory syndrome coronavirus 2 spike protein deposition followed by endothelial damage with activation of autophagy.

Concomitant thrombosis in patients with cellulitis as incidental finding.

BACKGROUND: Although inflammation and thrombosis are tightly connected, only 45% of patients with lower leg cellulitis receive anticoagulant therapy. Available data about the prevalence of concomitant deep venous thrombosis (DVT) in patients with cellulitis of the lower extremity is scarce and general guidelines regarding diagnosis and prevention of venous thromboembolism are missing. OBJECTIVE: We sought to determine how frequently DVT occurs as an incidental finding in patients with cellulitis and to provide recommendations for diagnostics and anticoagulant therapy. METHODS: Patients' records were analysed and 192 consecutive patients with cellulitis were included in this study. The prevalence of concomitant DVT was examined by duplex ultrasound, as well as comorbidities and risk factors. RESULTS: We detected thrombosis in 12.0% of the patients with lower leg cellulitis, of which 43.5% were located in a proximal vein and 52.2% in the veins of the calf. CONCLUSIONS: Our results clearly indicate that cellulitis is not only a differential diagnosis, but should be considered a risk factor for venous thrombosis. Therefore, prophylactic anticoagulation should be considered in patients suffering from cellulitis and a systematic screening for venous thrombosis in patients with cellulitis should be performed.

Microvascular Skin Manifestations Caused by COVID-19.

Hypercoagulability and vascular injury, which characterize morbidity in COVID-19 disease, are frequently observed in the skin. Several pathomechanisms, such as inflammation caused by angiotensin-converting enzyme 2-mediated uptake into endothelial cells or SARS-CoV-2-initiated host immune responses, contribute to microthrombus formation and the appearance of vascular skin lesions. Besides pathophysiologic mechanisms observed in the skin, this review describes the clinical appearance of cutaneous vascular lesions and their association with COVID-19 disease, including acro-ischemia, reticular lesions, and cutaneous small vessel vasculitis. Clinicians need to be aware that skin manifestations may be the only symptom in SARS-CoV-2 infection, and that inflammatory and thrombotic SARS-CoV-2-driven processes observed in multiple organs and tissues appear identically in the skin as well.