Abstract
Despite thousands of reported patients with
pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative
linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children
is associated with monogenic disorders of excessive
IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover,
SARS-CoV-2 spike protein and robust IFN-1 response
are seen in the skin of patients with pandemicassociated pernio, suggesting an excessive innate
immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may
elucidate the host mechanisms that drive a resilient
immune response to SARS-CoV-2 and could produce
relevant therapeutic targets.
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