Double Trouble with COVID toes
Despite the falling infection rates in the United Kingdom of COVID-19, in other countries, further increases in infections are currently being observed. In previous reports, the author has highlighted the issue of chilblain-like lesions [CLL] (or COVID toes) amongst predominantly younger patients, who frequently demonstrate limited or no symptoms of the disease which have been observed throughout the pandemic. A common feature of these patients is the high proportion of patients who test negative for the disease. In the bulletin of 23rd March 2021, it was reported that a proportion of patients are reporting persistent chilblains which is now considered to be a symptom of the long COVID syndrome.
This month, further work has been published in the literature, demonstrating a resurgence of the phenomenon as infection rates rise in many countries. Moreover, a recent paper  has highlighted confirmed cases of relapse of CLL in 10 patients (average age 15 years), both during the first and second waves of the infection. In all cases the serology and nasal pharyngeal swabs were negative. The explanation for this relapse are purely speculative but does fit with the favoured hypothesis that COVID-19 in younger patients leads to the release of interferon , known as the type one interferon pathway. The release leads to the rapid clearing of the infection before any immunity is developed and consequently, chilblains develop, particularly in the toes often with no other symptoms of COVID exposure. Consequently, upon second exposure to the virus, as there is no immunity generated from the first exposure, the cycle is repeated and interferon released resulting in further chilblain like lesions.
This hypothesis was strengthened by a study of 40 consecutive patients with CLL . All demonstrated negative findings when tested for the virus using polymerase chain reaction testing and only 12 (30%) had positive serology results for antibodies to COVID. However, all showed significant rises in interferon-α levels when tested against control patients with PCR positive and mild to severe symptoms of COVID suggesting that interferon release is a key aspect of chilblain development. This work has been reinforced by a second piece of research which demonstrated induction of the type one interferon pathway in three biopsies taken from patients with chilblains .
1. Recalcati, S., et al., Relapse of chilblain-like lesions during the second wave of coronavirus disease 19. Journal of the European Academy of Dermatology and Venereology, 2021. 35(5): p. e315-e316.
2. Lipsker, D., A chilblain epidemic during the COVID-19 pandemic. A sign of natural resistance to SARS-CoV-2? Med Hypotheses, 2020. 144: p. 109959.
3. Hubiche, T., et al., Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic. JAMA Dermatology, 2021. 157(2): p. 202-206.
4. Aschoff, R., et al., Type I Interferon Signature in Chilblain-Like Lesions Associated with the COVID-19 Pandemic. Dermatopathology (Basel), 2020. 7(3): p. 57-63.