From left to right: patients with COVID 19-associated chilblains (n = 19); nonhospitalized patients with nonsevere COVID-19 without CAC (n = 8); and critically ill patients with COVID-19 in the intensive care unit (n = 72). We confirmed that IFN-I signalling was increased in whole blood of patients with CAC but the kinetics of ISG over time were like those of SARS-CoV-2 infection without CAC. Since the onset of the SARS-CoV-2 pandemic, the direct causative role of the virus in COVID-19-associated chilblains (CAC) has remained under question due to the low rate of positivity to SARS-CoV-2 nasopharyngeal polymerase chain reaction (PCR) and blood serology.[1] Likewise, the suspected pivotal pathogenic role of upregulation of interferon type I (IFN-I) is mainly indirectly supported by assessment of I in situ i immune response.[2] From April 2020 to January 2022, we prospectively assessed children and adults with new-onset CAC seen in the dermatology, infectious diseases, and adult and paediatric emergency departments, as well as the intensive care unit of the University Hospital of Montpellier. [Extracted from the article]