Send Orders for Reprints to reprints@benthamscience.net Current Molecular Medicine 2022, 22, 563-566 563 LETTER TO THE EDITOR COVID-Toe - The Silent Symptom: Raising Awareness among Health Care Professionals and Community Nitesh Sanghai 1,* and Geoffrey K. Tranmer 1,2 1 College of Pharmacy, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB R3E 0T5, Canada; 2 Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada Dear Editor, During the current global pandemic, it is known that SARS-CoV-2 viral infections show different disease patterns and marked variability in host immune responses during the progression of the disease called COronaVIrus Disease 2019 (COVID-19). It is a typical respiratory syndrome (SARS) that emerged in China [1]. COVID-19 can cause a wide range of signs and symptoms, with clinical manifestations changing from patient to patient. Earlier in the pandemic, scientists considered only older patients [2, 3] to be vulnerable to COVID-19, but this has now become a myth. With the passage of time all ages have been shown to be susceptible to COVID-19 with varying degrees. Additionally, it has become an increasingly daunting task to recognize the clinical manifestations of SARS- CoV-2 viral infections in asymptomatic patients. Over the course of time, SARS-CoV-2 infections have been found to hijack the human body from head to toe and have baffled many in the health care community. Therefore, we hope to increase awareness in the health care community of an unusual symptom termed ‘COVID toe’. Secondly, we would also like to alert practitioners to be vigilant and diligent during the diagnosis of SARS-CoV-2 infections, as non-serious ‘COVID toe’ could develop into life-threatening COVID-19. We propose that in addition to physical distancing, it is now imperative to detect viral infections in the early stages of the disease to prevent further infection in the community and develop more serious symptoms [4]. ‘COVID toe’ is the latest unusual skin manifestation for patients that are infected with the novel coronavirus with unknown incidence and prevalence [5, 6]. This term COVID toe is likely to be a misnomer as the condition is also apparent in hand, lateral aspect of feet, and acral regions [7, 8]. Externally, it can present as a purple-red bumpy lesion, often associated with pain described as a burning sensation by the patients without any history of trauma. A typical clinical history is preceded by low-grade fever and tenderness. This unusual skin manifestation in COVID-19 is mostly restricted to otherwise asymptomatic patients instead of immunocompromised old-age COVID-19 positive patients in Intensive Care Units (ICU) [8]. In addition, there is a significant risk of false-negative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) tests in younger populations because of lower viral loads in the nasopharynx and therefore tested RT-PCR negative but were infected and seroconverted at 6-8 weeks [9, 10]. COVID-toe histologically is a combination of idiopathic pernio and Chilblain Lupus Erythematosus (CHLE), focal thrombi[6]. The similarity lies firstly in the presence of Superficial and deep perivascular lymphocytic infiltrates with perieccrine involvement—secondly, the presence of vacuolar interface and scattered necrotic keratinocytes. However, characteristic focal thrombosis can be seen in the case of COVID-toe, which is not characteristic of CHLE or idiopathic pernio [8, 11]. Dermatologists around the world have been attempting to identify a causal relationship between COVID-19 and chilblain-like lesions. Recently, the studies related to the cutaneous manifestation of COVID-19 in the younger population have increased [12]. However, the current understanding of the immune response between COVID-toe and COVID-19 is not unraveled. Chilbians like cutaneous manifestations are not common in younger populations; however, during the current pandemic, there are clinical reports which, showed the commonly occurring cutaneous manifestation in the younger population, mainly in the COVID-19 infected family, thereby acting as an asymptomatic carrier of COVID-19 [13]. Many reports of COVID-toes have been reported in the younger population in Italy during pandemic. In one case, a 16 year old patient presented with lesions on the fingers and toes, histologic examination showed edema with a deep lymphocytic infiltrate and perieccrine involvement. RT-PCR for SARS-CoV-2 via nasopharyngeal swab was positive [14]. In a second study of 63 patients with chilblain-like lesions in Italy, the median age reported was 14 years . The most commonly affected area were feet (85.7%) followed by feet and hands together (7%) and hands alone (6%). COVID-19 PCR was performed in 11 patients (17.5%), and serology was available in 6 (9.5%). Both tests were reactive in 2 cases (3.2%) [15]. Another, Italian prospective study *Address correspondence to this author at the College of Pharmacy, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB R3E 0T5, Canada; Tel: +14313380385; E-mail: Sanghain@myumanitoba.ca 1875-5666/22 $65.00+.00 © 2022 Bentham Science Publishers