Association Between Serum Soluble Programmed Death Ligand 1 Levels and Disease Severity in Patients with Crimean-Congo Hemorrhagic Fever

Crimean-Congo hemorrhagic fever (CCHF) is a severe viral infection that may lead to coagulopathy and multiorgan failure. Although the programmed cell death protein 1/programmed death ligand 1 (PD-L1) immune checkpoint pathway regulates excessive inflammation, the clinical significance of circulating soluble PD-L1 (sPD-L1) in CCHF is not well defined. The aim for the present study was to measure serum sPD-L1 levels in patients with CCHF and evaluate their association with disease severity and prognosis. This prospective study included 60 adults with confirmed CCHF and 30 healthy controls. Disease severity was classified using the Severity Scoring Index. Serum collected on admission was analyzed for sPD-L1, and routine laboratory values were recorded. Clinical and laboratory differences between severity groups were examined, and correlation and receiver operating characteristic analyses were performed. Neurological symptoms, fever, diarrhea, and bleeding were more common in moderate-to-severe cases. These patients had significantly lower platelet and fibrinogen levels and higher alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, international normalized ratio, and activated partial thromboplastin time values. Soluble PD-L1 levels were similar in healthy controls and mild cases but were markedly elevated in moderate-to-severe cases. Soluble PD-L1 accounted for more than half of the variation in severity scores (R2 = 0.556). Receiver operating characteristic analysis revealed strong discriminatory ability (area under the curve: 0.901), with a cutoff of 10.91 ng/mL yielding 96.7% sensitivity and 80% specificity. In conclusion, elevated sPD-L1 levels are closely associated with disease severity in CCHF. Soluble PD-L1 may have prognostic value, although this association should be confirmed in larger studies.