Introduction
The new coronavirus (SARS-COV-2) that causes COVID-19 disease was first detected in Wuhan, China in December 2019 and rapidly spread to more than 200 countries.1 Although COVID-19 is generally characterized by respiratory system symptoms such as fever, sore throat, shortness of breath, and cough, cases presenting with atypical symptoms such as abdominal pain, headache, diarrhea, smell and taste disorders, musculoskeletal pain and skin lesions have been widely reported recently.2
Severe COVİD-19 disease is an uncontrolled response of the immune system to infection, in which high levels of circulating cytokines lead to generalized inflammatory response with failure of at least one organ function and high mortality rates.3 Many COVID-19 related mortality biomarkers such as D-Dimer, C-reactive protein (CRP), Ferritin, pentraxin-3 and proinflammatory cytokines elevation have been demonstrated.4-10 However, the search for different disease-specific biomarkers continues.
Midkine (MK) is a multifunctional cytokine, expressed primarily in midgestation. It is a heparin-binding growth factor sensitive to retinoic acid released from various cell types during embryogenesis. Promotes angiogenesis, cell growth and cell migration. Midkine is also expressed in various malignancies, suggesting that it may play a role in tumorigenesis, perhaps through its effects on angiogenesis. Cytokines and growth factors are classified into structurally related protein families such as the fibroblast growth factor family.11 In addition, MK organizes the proliferation, differentiation, survival, adhesion, migration and gene expression of immune cells. At the same time, MK is a mitogenic, antiapoptotic, migrating, chemotactic, angiogenic and fibrinolytic molecule that plays a role in controlling the inflammatory response.12 MK can alleviate hypoperfusion and myocardial cell damage due to hypoxia, as well as promote angiogenesis in myocardial infarction.13 However, it may accelerate tubular necrosis in drug or autoimmune kidney damage11 and pulmonary fibrosis due to acute respiratory distress syndrome (ARDS) .14 The interesting issue about MK is that it has been shown in studies that it has bactericidal, antifungal and antiviral effects in some viruses such as herpes simplex and human immunodeficiency virus (HIV).15-17
COVID-19 is a new disease and many proinflammatory cytokines and other acute phase proteins levels have been found to correlate with poor prognosis in the literature. However, there are no specific biomarkers in the prognosis and surveillance of COVID-19.18 The aim of our study was to investigate MK levels in COVID-19 infection and to explore whether there is a relationship between the prognosis of patients and midkine levels.