Negative tests for SARS‐CoV‐2 infection do not rule out its responsibility for chilblains

Abstract

We read with great interest the report of Le Cleach et al discussing chilblains as a manifestation of COVID‐19 pandemic. They reported 311 patients with acral lesions occurring during the COVID‐19 lockdown in France. The most frequent clinical presentation of these acral lesions was typical chilblains. Among the 150 patients with RT‐PCR testing and/or serology, only 10 had confirmed COVID‐19. They concluded that there is no evidence of SARS‐CoV‐2 infection in the large majority of patients with acral lesions. They hypothesized that the situation could be due to the media stating that chilblains were caused by SARS‐CoV‐2 infection and leading to a higher rate of consultation or the lockdown leading to more inactivity and long periods at home barefoot on a cold floor 1 .

Chilblains in a child with confirmed SARS‐CoV‐2 infection: a red flag for late‐onset skin manifestation in previously infected individuals

“…Nevertheless, specific T cells have been detected in antibody-seronegative individuals with a history of asymptomatic and mild COVID-19. 9 Memory T-cell responses can occur in the absence or presence of circulating antibodies, consistent with a non-redundant role as key determinants of immune protection against COVID-19. T-cell responses are more common than circulating antibodies in mild and asymptomatic COVID-19 patients.…”

Six months into the pandemic. A review of skin manifestations in SARS‐CoV ‐2 infection

“…The real link between mild, acral chilblain‐like lesions, and SARS‐CoV‐2 infection is widely disputed, since patients were often negative when tested by RT‐PCR on nasal swabs or by serological tests. Anyway, this could be explained as an Interferon type I induced (IFN‐I) protein upregulation, since active viral replication is not necessary to mount an efficient IFN response in SARS‐CoV infection; inhibition of coronavirus replication by Interferon‐induced trans‐membrane protein and depletion of B cells caused by high expression of IFN‐I may explain negative PCR and serological tests, respectively 36 …”

Impaired type I interferon response in SARS‐CoV‐2 infection: looking through the cutaneous window

“…The clinical and histopathological similarities of COVID‐19 chilblains to the acral cutaneous lesions observed in genetic interferonopathies, notably familial chilblain lupus and STING‐associated vasculopathy with onset in infancy (SAVI), 6 suggest a pivotal pathogenic role of upregulation of type I interferon response in causing these skin lesions. These data have prompted the hypothesis of a pathophysiological mechanism of COVID‐19 chilblains that can be summarized as follows: high production of type I interferon at the onset of viral infection – perhaps a hallmark in children, young adults and predisposed patients – is associated with the early and rapid inhibition of the replication and clearance of the virus, accounting for the mild disease course, the usually negative PCR test positivity and the negativity of serologies 7,8 …”