Introduction
In the last days of 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a disease in Wuhan, China, which was later named as coronavirus infection disease 2019 (COVID-19) and became a global health problem (1). COVID-19 can present with mild flu-like to severe symptoms such as acute respiratory distress syndrome (ARDS), septic shock, poorly controlled metabolic acidosis, coagulation dysfunction, and multi-organ failure (2). Therefore, understanding specific and different symptoms and signs of the disease is of great importance. To the best of our knowledge, many of the symptoms and complications corresponded to the COVID-19 are caused by cytokines and mediators of the immune system induced by the infection. In this regard, cytokine storm is the result of the overproduction of major pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β that can produce hypercoagulable state and multiple organ dysfunction (3).
Similar to other types of ARDS, there is a hypercoagulable state in COVID-19 patients. This inflammatory condition, as a result of endovascular damage, increased platelet activity, and coagulation cascade causes the phenomenon of immuno-thrombosis (4). Consequently, clot formation can be observed in large and small blood vessels, along with in situpulmonary thrombosis and also thromboembolism (PTE) (5). In other words, overactivation of the coagulation pathway that occurs during the time of cytokine storm may be the result of increased thrombin activities. Furthermore, thrombin can play other roles in the inflammatory process by proteinase-activated receptors (PARs) (3). On the other hand, Yan Zhang et al. reported antiphospholipid syndrome (APS) in COVID-19 (6). Livedo reticularis, that also has been reported in COVID-19 (7), is related to APS and cold agglutinin disease; accordingly, viral infection is one of the causes of cold agglutinin formation (8). Therefore, cold hemagglutinin disease should also be considered in patients with COVID-19 who present with this skin manifestation.
Furthermore, acrocyanosis has been described in critically ill patients with COVID-19 because of excessive coagulation status (9). Indeed, acrocyanosis and digital necrosis have previously been reported in many rheumatologic disorders and vasculitis, including ANCA-associated vasculitis, cryoglobulinemia vasculitis, lupus-related vasculitis, vasculopathy caused by APS, and also fingertips necrosis due to scleroderma vascular involvement as well as Raynaud’s phenomenon (10-12). From a physiologic point of view, gangrene may occur by impaired blood flow and insufficient healing process of digital wounds which is associated with the increasing levels of C-reactive protein (CRP) (11). Here, we describe two cases of critically ill patients with COVID-19 who developed digital acrocyanosis and subsequently fingertips necrosis during their illness.