Milovanovic, Branislav (23474625200)Branislav (23474625200)MilovanovicMarkovic, Nikola (59305731500)Nikola (59305731500)MarkovicPetrovic, Masa (57219857642)Masa (57219857642)PetrovicZugic, Vasko (57640909700)Vasko (57640909700)ZugicOstojic, Milijana (59553942800)Milijana (59553942800)OstojicDragicevic-Antonic, Milica (58773069100)Milica (58773069100)Dragicevic-AntonicBojic, Milovan (7005865489)Milovan (7005865489)Bojic2025-06-122025-06-122025https://doi.org/10.3390/v17030427https://www.scopus.com/inward/record.uri?eid=2-s2.0-105001367430&doi=10.3390%2fv17030427&partnerID=40&md5=77fd8e3b8169c1adc44c8d80384eda07https://remedy.med.bg.ac.rs/handle/123456789/604Background/Objectives: Syncope is a common clinical occurrence, with neurally mediated and orthostatic types accounting for about 75% of cases. The exact pathophysiological mechanisms remain unclear, with recent evidence suggesting autonomic nervous system damage and a potential infectious etiology. This study aimed to examine the role of infection in the development of syncope and orthostatic hypotension (OH). Methods: The cross-sectional study included 806 patients from the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje”. Patients were divided into three groups: unexplained recurrent syncope (n = 506), syncope with OH during the head-up tilt test (HUTT) (n = 235), and OH without a history of syncope (n = 62). All participants underwent the HUTT, and 495 underwent serological testing for various microorganisms. Data were analyzed using chi-squared tests and binary and multinomial logistic regression. Results: The HUTT was positive in 90.6% of patients with syncope and OH, compared with 61.6% with syncope alone (p < 0.001). Serological testing revealed that 57.85% of syncope patients, 62.9% of syncope with OH patients, and 78% of OH patients had positive IgM antibodies to at least one microorganism. Multivariate analysis indicated that IgM antibodies to Coxsackievirus and Epstein–Barr virus were significant predictors of OH. Conclusions: This study demonstrated a potential association between infections and syncope/OH. Further investigation into the role of infectious agents in autonomic dysfunction is warranted to clarify the underlying mechanisms of syncope and OH. © 2025 by the authors.autonomic dysfunctionhead-up tilt testneurocardiologysyncope