Aim: The COVID outbreak is a serious health problem affecting socio-economic life and healthcare systems worldwide. Although the role of Semaphorins in some diseases is relatively known, the association of these molecules with the pathogenesis of COVID-19 remains unclear. Therefore, we aimed to investigate the relationship of Semaphorins (Sema3A, Sema4A, Sema4D and Sema7A) with biochemical and inflammatory alterations and their roles in predicting the presence of disease and disease severity in COVID-19 patients.

Material and Method: A total of 144 COVID-19 patients and 20 healthy individuals were enrolled in the current study. Serum Semaphorins were analyzed using Enzyme-linked Immunosorbent Assay. Other laboratory parameters were measured using routine laboratory techniques.

Results: Sema3A concentrations were elevated in both patients with severe and non-severe COVID-19 groups compared with healthy controls (p<0.0001). Sema4A levels were significantly decreased in patients with the severe COVID-19 group (p=0.002). Sema3A was negatively correlated with routine hematological markers such as EOS, RBC, HGB, HCT and MCV. Further, Sema3A was positively correlated with coagulation markers such as D-dimer and fibrinogen and the inflammatory markers, such as ESR, CRP, PCT and ferritin and biochemical markers such as ALT, AST, BUN, CK and LDH. Sema4A was negatively correlated with WBC, while it was positively correlated with LYM and HCT. Sema3A levels over 3.03 ng/mL and Sema4A concentrations of less than 11.8 ng/mL may predict the presence of COVID-19 (p<0.0001, p=0.02, respectively).

Conclusion: Our data presented here suggest that Sema3A and Sema4A could be diagnostic markers for COVID-19 and may have importance in the clinical management of the disease.