SARS-CoV-2 Endothelial Infection Causes COVID-19 Chilblains

Histopathological, Immunohistochemical and Ultrastructural Study of Seven Paediatric Cases

I. Colmenero; C. Santonja; M. Alonso-Riaño; L. Noguera-Morel; A. Hernández-Martín; D. Andina; T. Wiesner; J.L. Rodríguez-Peralto; L. Requena; A. Torrelo


The British Journal of Dermatology. 2020;183(4):729-737. 

In This Article

Abstract and Introduction


Background: Chilblains ('COVID toes') are being seen with increasing frequency in children and young adults during the COVID-19 pandemic. Detailed histopathological descriptions of COVID-19 chilblains have not been reported, and causality of SARS-CoV-2 has not yet been established.

Objectives: To describe the histopathological features of COVID-19 chilblains and to explore the presence of SARS-CoV-2 in the tissue.

Methods: We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID-19 pandemic. Immunohistochemistry for SARS-CoV-2 was performed in all cases and electron microscopy in one.

Results: Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS-CoV-2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy.

Conclusions: Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS-CoV-2. Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID-19 chilblains and perhaps also in a group of patients severely affected by COVID-19 presenting with features of microangiopathic damage.


Acral purpuric lesions identical to chilblains are being seen with an exceedingly high frequency in children and young adults during the coronavirus disease 2019 (COVID-19) pandemic worldwide.[1–3] They have been the subject of numerous mentions in the nonspecialized media, usually under the designation 'COVID toes'.[4] Most patients have been negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when tested by polymerase chain reaction (PCR) of nasopharyngeal and oropharyngeal swabs, and < 50% have a history of exposure to positive household contacts or previous history of mild upper respiratory or gastrointestinal symptoms.[1]

Despite the high number of cases, a definite causative role for SARS-CoV-2 has not been proven. Several pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors.[5,6] On the other hand, the histopathological features of COVID-19-related chilblains and the presence of SARS-CoV-2 in the lesions have not been addressed.

We present the histopathological, immunohistochemical and ultrastructural features of seven children with chilblains presenting shortly after the peak of the COVID-19 outbreak in Madrid, Spain, and propose a causative role for SARS-CoV-2.