key: cord-0896910-g6oz48q4 authors: Colmenero, I.; Santonja, C.; Alonso‐Riaño, M.; Andina, D.; Rodríguez‐Peralto, J.L.; Requena, L.; Torrelo, A. title: Chilblains and COVID‐19: why SARS‐CoV‐2 endothelial infection is questioned: reply from authors date: 2020-08-15 journal: Br J Dermatol DOI: 10.1111/bjd.19491 sha: 4f505af4a72adb0c2f3dba04d05fc4f26a26b6de doc_id: 896910 cord_uid: g6oz48q4 We thank Dr Baeck et al. for their interest in our recent article published by BJD(1). The negative RT‐PCR in nasopharyngeal swabs in patients with COVID‐19 chilblains has been extensively acknowledged in the literature, however a significant proportion of patients had mild systemic symptoms or contact with confirmed or suspected cases (2). We thank Dr Baeck et al. for their interest in our recent article published by BJD 1 . The negative RT-PCR in nasopharyngeal swabs in patients with COVID-19 chilblains has been extensively acknowledged in the literature, however a significant proportion of patients had mild systemic symptoms or contact with confirmed or suspected cases 2 . Magro et al. 3 , recently demonstrated SARS-CoV-2 in skin biopsies of 3 patients with COVID19related perniosis by immunohistochemistry (SARS CoV-2 envelope protein colocalised with SARS CoV-2 membrane protein) and RNA-scope together with evidence of type I interferon signalling activation. The authors propose that a strong type I interferon response may speed viral elimination, explaining the reported negativity for RT-PCR and serological tests. Low sensitivity of the serological tests in asymptomatic patients could also explain the negative results. It is unclear whether serological tests can detect lower antibody levels likely seen in mildly symptomatic or asymptomatic patients 4 . Although limited to the skin of the distal extremities, the vascular damage seen in COVID-19 chilblains is severe enough to produce a lymphocytic vasculitis with endothelial disruption, microthrombosis and localised ischemia. Why the lesions in these patients are limited to the distal feet and hands is still unknown. We reaffirm in our statement that immunohistochemistry for detection of SARS-CoV/SARS-CoV-2 remains restricted and subject to cautious interpretation. The images showed by Baeck et al. show suboptimal non-specific reactivity. In our hands, using an antibody directed against the spike protein of SARS/SARS-CoV-2, after optimisation of the staining, we obtained a clean background, and our negative controls showed entirely negative endothelial reactivity. We This article is protected by copyright. All rights reserved acknowledge that we have no experience with the SARS-CoV-2 NP antibody used by the Baeck et al. The observation that our pictures show positivity limited to relatively healthy vessels is interesting. In fact, in our cases, not all the vessels showed the same degree of positivity, and heavily inflamed vessels appeared to show a lower expression than mildly inflamed ones. Clearance of viruses by the inflammatory process may be a potential reason for this. Definitive characterisation of SARS-CoV-2 virions requires immuno-EM. Unfortunately, we do not have remaining tissue adequately processed to perform this study, and we have not seen any other patient presenting with chilblains since the beginning of May. We are prepared to preform SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultraestructural study of 7 paediatric cases Chilblains in children in the setting of COVID-19 pandemic The differing pathophysiologies that underlie COVID-19 associated perniosis and thrombotic retiform purpura: a case series Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev Spectrum of clínico-pathological findings in COVID-19 induced skin lesions: demonstration of direct viral infection of the endotelial cells Accepted Article