From Your Nose to Your Toes: A Review ofSevere Acute Respiratory SyndromeCoronavirus 2 Pandemic‒Associated Pernio

Abstract

Despite thousands of reported patients withpandemic-associated pernio, low rates of serocon-version and PCR positivity have defied causativelinkage to severe acute respiratory syndrome coro-navirus 2 (SARS-CoV-2). Pernio in uninfected childrenis associated with monogenic disorders of excessiveIFN-1 immunity, whereas severe COVID-19 pneu-monia can result from insufficient IFN-1. Moreover,SARS-CoV-2 spike protein and robust IFN-1 responseare seen in the skin of patients with pandemic-associated pernio, suggesting an excessive innateimmune skin response to SARS-CoV-2. Understand-ing the pathophysiology of this phenomenon mayelucidate the host mechanisms that drive a resilientimmune response to SARS-CoV-2 and could producerelevant therapeutic targets.