Immune response to SARS-CoV-2 could be responsible for ‘COVID toes’
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An immune response may be responsible for “COVID toes,” chilblain-like lesions associated with COVID-19 infection, according to a study published in the British Journal of Dermatology.
COVID toes, which appear as purple or red lesions on the toes or hands, is a dermatologic symptom of COVID-19 that has appeared mostly in younger infected individuals but could affect anyone with the virus.
“A range of cutaneous manifestations have been described in association with SARS-CoV-2 infection during the COVID-19 pandemic. Among them chilblain-like lesions (CLL) have been occurring more frequently than expected,” Laure Frumholtz, MD, of the dermatology department at Hôpital Saint-Louis in Paris, and colleagues wrote. “The aim of this study was to analyze deeply the immunological and vascular pathophysiology of CLL during the COVID-19 outbreak compared with [seasonal chilblains].”
All patients with first-time CLL at Hôpital Saint-Louis between April 9, 2020, and April 16, 2020, were included in this non-interventional observational study.
Polymerase chain reaction tests for SARS-CoV-2 were negative for all 50 patients; however, 29 (58%) had extracutaneous COVID-19 symptoms including asthenia (n = 14), fever (n = 11), upper airway and ear-nose-throat symptoms (n = 16), cough (n = 9), dyspnea (n = 2) and anosmia (n = 1).
CLL were present on the toes in 86% of cases and on the fingers in 24% of cases.
Blood samples collected from each patient were tested for whole blood count, hemostasis, IgA level, isotypes of IgG and IgA antineutrophil cytoplasmic antibodies, antinuclear antibodies, anti-double-stranded DNA antibodies, anti-double-stranded DNA antibodies, cryoglobulinemia, cryofibrinogen, and anticardiolipin and anti-beta-2-glycoprotein-I IgG antibodies (IgM and IgG).
Skin biopsies were also performed in 13 patients.
Comparisons of skin histological characteristics of 13 patients with CLL and 13 with seasonal chilblains before the pandemic were performed, and all samples were found to have lymphocytic infiltration around blood vessels.
Of the CLL group, 73% had a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies, which is connected with a systemic immune response.
In addition, the CLL group had a higher IgA tissue deposition.
“This study illustrates that both the immune system and endothelial cells play a critical role in the genesis of CLL,” Frumholtz and colleagues wrote.
The researchers further said their “findings support an activation loop in the skin in CLL, which associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestation.”
Perspective
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In their article “Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak,” Frumholtz and colleagues provide us with key additional insights into the pathophysiology of pernio/chilblains during the COVID-19 pandemic, also known as “COVID toes.”
The study adds to our knowledge regarding the role of type I interferon in the development of these lesions, supporting the hypothesis that a robust host immune response to SARS-CoV-2 can trigger pernio/chilblains in some patients. Additionally, the authors found a high prevalence of IgA antineutrophil cytoplasmic antibodies in these patients, which has not been previously noted but is consistent with prior findings that these patients often have IgA antibody profiles (and may not test positive on commercial IgM or IgG antibody tests).
Much of the research focus globally on COVID-19 has been on patients with severe disease. However, patients with mild or moderate disease, such as patients included in this study with COVID toes, also hold important immunological and clinical clues regarding the virus.
Dermatologists continue to have an important role in the pandemic: in early detection of SARS-CoV-2 in patients with rashes that may be the first presenting sign or symptom of the virus, such as urticaria or morbilliform eruptions; in treating patients with dermatologic manifestations of COVID-19; and, more recently, in recognizing COVID-19 vaccine skin reactions, which are for the most part self-limited, therefore allowing us to provide reassurance to patients regarding the safety and importance of COVID-19 vaccines.
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