Investigating infection as a potential cause in the etiology of syncope

Abstract Background/Introduction Syncope is a common clinical event, defined as a transient loss of consciousness due to cerebral hypoperfusion, often linked to autonomic nervous system (ANS) dysfunction. Neurally mediated and orthostatic syncope account for around 75% of cases, frequently associated with autonomic dysfunction, which is well-documented in conditions like diabetes and neurological disorders. However, the cause of ANS dysfunction in many patients remains unclear. Emerging evidence suggests that infections—such as Lyme disease, COVID-19, and Epstein-Barr virus—may contribute to ANS damage and, in turn, to syncope or orthostatic hypotension (OH). Purpose This study investigates the potential role of infections in the development of syncope and OH, with a focus on autonomic dysfunction. Methods This cross-sectional study included 806 patients from the Neurocardiological Laboratory of our Institute. Participants were grouped into three categories: unexplained recurrent syncope (n = 506), syncope with OH during Head-Up Tilt Test (HUTT) (n = 235), and OH without a history of syncope (n = 62). All patients underwent 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 to 61.6% in those with syncope alone (p 0.001). Serological tests showed that 57.85% of the syncope group had positive IgM antibodies, with Borrelia spp. (14.5%) and HSV1 (12.4%) being most common. In the syncope with OH group, 62.9% tested positive for IgM antibodies, predominantly for Coxsackievirus (21.6%). The OH without syncope group showed 78% positivity, mostly for Coxsackievirus (28.8%). Statistically significant differences were found in the prevalence of Mycoplasma pneumoniae, CMV, EBV, and HSV1 across groups. Multivariate analysis revealed that female sex and CMV IgG antibodies were predictors for a positive HUTT. Male gender and IgM antibodies to Parvovirus B19 predicted hypertensive reactions, while female gender, IgM antibodies to Coxsackievirus, and EBV were predictors for OH. Multinomial logistic regression showed that positive IgM antibodies to Coxsackievirus and Borrelia spp. increased the likelihood of being classified into the syncope with OH and OH without syncope groups. Conclusions This study suggests a potential association between infections and syncope/OH, indicating that infectious agents may contribute to autonomic dysfunction. Further research is needed to confirm the role of infections in the pathogenesis of these conditions.