The importance of neopterin in COVID-19: the prognostic value and relation with the disease severity


Severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2] infection has been spreading rapidly around the world since it’s first appeared in China in late 2019. The data show that approximately percent 80 of COVID-19 patients have mild disease percent 20 require hospitalization, and approximately percent 5 need intensive care admission. COVID-19 has a poor prognosis in elderly, male patients and, in patients with comorbidities such as diabetes, cardiovascular disease, or Chronic Obstructive Pulmonary Disease [COPD]. In patients infected with SARS-CoV-2, hyper-inflammation and coagulopathy are known to be associated with disease severity and death. Elevated levels of inflammatory markers, including C-reactive protein, ferritin, D-dimer, inflammatory cytokines, and chemokines, and elevated neutrophil to lymphocyte ratios are associated with disease severity and mortality from COVID-19. High levels of circulating cytokines, profound lymphopenia, substantial mononuclear cell infiltration in the lungs and other organs have been reported in severe cases compared to mild COVID-19 cases. Previous studies have shown that in severe cases, the proportion of mononuclear phagocytes increased and the composition of macrophages changed in favor of monocyte-derived macrophages. As a result, high levels of cytokines linked to macrophage activation including interferon- [IFN-], have been reported in SARSCoV-2 patients. NPT produced by macrophages on stimulate with IFN-, a cytokine important in the antiviral immune response. Serum NPT levels reflect the activation phase of the cellular immune system, which is important in the pathogenesis and progression of various diseases. Previous studies have shown an association between serum NPT levels and prognosis in certain viral infections, such as influenza, human immunodeficiency viruses, hepatitis C virus, and dengue fever virus. High levels of circulating cytokines have been reported in patients with severe COVID-19. Therefore, targeting of NPT in SARS-CoV-2 infection may be important for early prognosis of disease progression and timely treatment of infected patients. Serum NPT levels have been measured to assess the immune activation in several diseases, but only a few studies have been conducted on individuals infected with SARS-CoV-2. Therefore, this review is intended to elucidate the importance of NPT as a diagnostic and prognostic marker in COVID-19 patients.

In the present pandemic, it is frequently observed that cytokine storm occurs in patients with COVID-19 infection. When respiratory epithelial tissue is infected by COVID-19 infection, inflammatory cytokines such as IL-1, IL-6, IL-8, IL-12, TNF- and other chemokines locally realized. subsequently, monocytes, macrophages, neutrophils, DCs, and NK cells are recruited by cytokines resulting in activation CD4+ and CD8+ T cells to synthesis IFN- and TNF-, which induce lung injury. Furthermore, high production IL-2, IFN-, GM-CSF, and TNF- leads to anemia by macrophage activation and erythro-phagocytosis [92,102]. IFN- is considered as a glycosylated protein of 25 kDa [103]. It is well established that IFNs are categorized into three categories; type I [IFN ], type II [IFN] and type III [IFN]